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Endocrine Physiology

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paracrine
What are hormones called that act primarily on neighboring cells?
autocrine
What are hormones called that act on the cell that released them?
adipose tissue
growth hormone causes the growth of all tissues except?
bioassay
What is a cumbersome assay that gives variable results depending on the physiological state of the animal, organ, tissue, or cell being used?
radioimmunoassay
An assay is performed in which an Ab to a hormone is used to precipitate hormone, and the amount of radioactive hormone that is precipitated is used to calculate the amount of nonradioactive hormone in the body. What kind of assay is this?
ELISA
An assay is performed in which plastic wells coated with Abs to a hormone bind the hormone. A second Ab recognizes the complex between the first Ab and the hormone. A third Ab recognizes the second Ab, and the third Ab is conjugated to horseradish peroxidase. Then the oxidation of a dye to a differently colored product is measured. What kind of assay is this?
minutes
What is the half-life, in general, of polypeptide hormones?
hours
what is the half-life, in general, of steroid hormones?
seconds
what is the half-life, in general, of epinephrine and norepinephrine?
days
what is the half life of thyroid hormones?
seconds
what is the half-life of prostaglandins, leukotrienes, and NO?
endocytosis
what is the main process of polypeptide hormone degradation in the bloodstream?
forming delta-5-pregnenolone
what is the rate-limiting step in the formation of steroid hormones from cholesterol?
polar in liver
how are steroid hormones removed from the body?
uptake, liver
the two ways in which catecholamines are inactivated?
thyroid follicular cells
in what kind of cells are thyroid hormones produced?
thyroglobulin
What is the large protein containing many tyrosines produced by thyroid follicular cells?
thyroid peroxidase enzymes
What enzymes couple iodine to the tyrosines in thyroglobulin?
T3
What is the more active of the thyroid hormones?
steroid hormones, T3
What types of hormones bind to intracellular receptors that translocate into the nucleus?
adenyl cyclase
What enzyme converts ATP to cAMP when activated by a G protein?
protein kinase A
cAMP binds to the regulatory subunit of what enzyme?
phosphodiesterase
what enzyme helps regulate the cAMP cascade by degrading cAMP?
ER, extracellular space
what are two places from which calcium can be released into the cytoplasm to increase the intracellular Ca2+ concentration?
Protein Kinase C
What enzyme is activated by increased cytosolic calcium?
serine, threonine
What are the two amino acids phosphorylated by protein kinases A, C, and G?
cGMP
What is an important second messenger in the actions of acetylcholine on liver, heart, and smooth muscle?
tyrosine
Some polypeptide hormone receptors (such as the one for insulin) are kinases that phosphorylate proteins an what amino acid residue?
calmodulin
what is the protein that binds to calcium to from a complex that activates other enzymes?
IP3, DAG (inositol triphosphate and diacylglycerol)
fatty acids are degraded by phospholipase C to form what two molecules?
protein kinase C
diacylglycerol directly binds and activates what protein?
Ca release from ER
what does inositol triphosphate do?
ligands
What is another name for signaling molecules?
yes
Is signal transduction by second messengers a flexible process?
amplify
Do second messenger systems amplify or dampen the original signal?
F (signaling is pleiotropic)
T/F one ligand generates one response
adrenal cortex
Where is cortisol produced?
calcium
Vitamin D regulates metabolism of what molecule?
DNA
All intracellular steroid hormone receptors are structurally related and contain a domain that binds what?
heat shock
the inhibitory protein complex normally bound to intracellular steroid receptors often contain what kind of protein?
ion channel-linked, G protein-linked, enzyme-linked
Name the three general kinds of cell-surface receptors.
ion channel-linked
what kind of cell surface receptor is involved in rapid synaptic signaling between electrically excitable cells?
alpha
Which subunit of a G-protein is bound to GDP and has GTPase activity?
Gs
What are G proteins involved in enzyme activation called?
beta-adrenergic receptors
What receptors mediate some of the actions of adrenaline and noradrenaline AND involve activation of adenylate cyclase?
alpha2-adrenergic
What receptors inhibit adenylate cyclase when adrenaline binds to them?
alpha
what subunit differs between inhibitory G proteins and stimulatory G proteins?
protein kinase A (A-kinase)
What protein is present in all animal cells and is thought to account for virtually all effects of the second messenger cAMP?
CREB
What transcription factor is phosphorylated by cAMP, causing it to regulate gene expression in the nucleus?
phosphorylase kinase
What enzyme is phosphorylated by protein kinase A, which then phosphorylates glycogen phosphorylase?
glycogen synthase
What enzyme is inhibited when phosphorylated by protein kinase A, which performs the final step in glycogen synthesis?
I
What serine/threonine phosphatase regulates cAMP response and dephosphorylates many of the enzymes phosphorylated by protein kinase A?
IIA
What serine/threonine phosphatase that has a broad specificity and seems to be the main phosphatase responsible for reversing many of the phosphorylations catalyzed by serine/threonine kinases?
IIB
What serine/threonine phosphatase is called calcineurin, is activated by Ca, and is especially abundant in the brain?
fall
In the visual system, does receptor activation by light cause a rise or fall in cyclic nucleotide?
rhodopsin
What is a seven-membrane receptor activated by light photons instead of molecules?
all-trans-retinal
11-cis-retinal, a chromophore covalently attached to rhodopsin, isomerizes to what molecule when it absorbs a photon?
transducin
Activation of rhodopsin results in activation of G protein _____.
cGMP phosphodiesterase
the alpha-t subunit of G-protein transducin activates this enzyme
cGMP
When this molecule is dissociated from the plasma membrane sodium channels in cells of the eye, they close, converting a light signal to an electrical one.
inhibits
The neurotransmitter released by retinal neurons activates or inhibits neuron?
blocks neuron inhibition
light causes neurons to be inhibited or blocks neuron inhibition?
NO
An intracellular signaling molecule that diffuses across cell membranes and binds directly to guanylyl cyclase to directly regulate its activity.
relax
NO causes smooth muscle cells to do what?
guanylyl cyclase
the enzyme that produces cyclic GMP
Ca-ATPase
A protein found in the plasma membrane of all eukaryotic cells that pumps calcium out of the cell
muscle and nerve cells
What cells have an additional Ca pump in their plasma membrane that couples the efflux of Ca to the influx of Na (Na driven Ca antiport)?
ER
A Ca pump can be found where in addition to the plasma membrane, allowing uptake of Ca from the cytosol even when its level are low?
inner mitochondrial membrane
In the case of rising intracellular calcium due to cellular damage, a low-affinity, high capacity Ca pump found where becomes activated?
phosphatidylinositol
The two most important inositol phospholipid second messengers are phosphorylated derivatives of what molecule, a minor phospholipid in membranes?
PI-phosphate and PI-bisphosphate
The two most important inositol phospholipids.
PI-bisphosphate
The hydrolysis of what inositol phospholipid is very important in signal transduction?
yes
Do G-proteins ever utilize the PIP2 pathway?
phospholipase C-beta
The enzyme that cleaves PIP2 to generate IP3 and DAG.
Gq
The trimeric G protein that activates phospholipase C-beta.
plasma membrane
Protein kinase C translocates from the cytosol to where after the initial rise in Ca levels, where it is activated by a combination of Ca and DAG?
1
Most enzyme-linked cell surface receptors pass through the plasma membrane how many times?
yes
Can enzyme-linked cell surface receptors have phosphatase or protease activity?
tyrosine
Phosphorylation cascades involve two main types of protein kinases: serine/threonine kinases and ______ kinases.
ras
Both kinase linked receptors and G protein linked receptors often activated a small monomeric G protein called ______.
Raf
Kinase bound by ras that activates a kinase cascade including Mek and Map Kinase.
Elk-1
A transcription factor regulated by Map Kinase.
Epo
A cytokine that activates Jak kinases associated with its receptor.
STAT
Activation of a Jak kinase results in recruitment and subsequent phosphorylation of ______ proteins, which then dimerize and translocate to the nucleus to regulate gene transcription.
red blood cells
Erythropoietin (Epo) utilizes the Jak/STAT pathway to increase the production of ________.
SOCS
Proteins activated by STATS to terminate signaling from the Epo receptor.
collecting duct
target tissue of ADH
breast, uterus
target tissues of oxytocin
breast, ovaries
target tissues of prolactin
thyroid
target tissue of thyroid stimulating hormone
ovaries, testes
target tissues of LH and FSH
adrenal cortex
target tissue of ACTH
skin
target tissue of MSH
sensory neurons
target tissue of endorphins
hypothalamus
hormones secreted by the posterior pituitary are synthesized by neurosecretory cells whose cell bodies actually lie in the _____
F (the hormones will return when the axons regenerate and reach new capillary beds)
T/F removing the pituitary will result in permanent of ADH and oxtyocin
osmolarity, volume
increased plasma _____ or decreased plasma _____ will cause ADH release
ADH, oxytocin
the two hormones released by the posterior pituitary
growth hormone
hormone released by anterior pituitary that promotes growth and differentiation of many different tissues
IGF-1 (insulin-like growth factor-1)
in the presence of growth hormone the liver secretes ________, which is what actually causes the growth of most tissues
gigantism
GH excess in childhood leads to ________.
acromegaly
GH excess in adults leads to ______.
insulin
GH triggers lipolysis by reducing adipose tissue sensitivity to ______.
prolactin
A growth hormone-related hormone produced by anterior pituitary that promotes lactation in the breast (and is required for spermatogenesis in men).
prolactin, insulin, cortisol
three hormones required for lactation
oxytocin
hormone required to make milk available to a baby
F (women only)
T/F nipple stimulation results in prolactin release in both men and women
insulin
prolactin and placental lactogen contribute to the ____ resistance that is normally associated with late pregnancy.
glycoprotein
LH, FSH, and TSH are produced by the anterior pituitary and known as ______ hormones
alpha
the ______ subunits for the glycoprotein hormones are similar
corticotrophin
adrenocorticotropic hormone (ACTH), melanocyte stimulating hormone (MSH), and certain endorphins and enkaphalins are produced by the anterior pituitary and known as ______-related proteins
ACTH
the hormone produced by the anterior pituitary that stimulates the adrenal cortex to secrete glucocorticoids
opiate
the endorphins and enkephalins produced by the anterior pituitary have ____-like actions that reduce sensitivity to pain
MSH
the hormone produced by the anterior pituitary that causes darkening of the skin
Cushing's
over production of glucocorticoids causes ______ syndrome
Addison's
under produciton of glucocorticoids causes _______ disease
TRH
Hypothalamic releasing hormone that stimulates release of TSH and PRL
GnRH
Hypothalamic releasing hormone that stimulates release of LH and FSH
SST
Hypothalamic releasing hormone that inhibits release of GH and TSH
Dopamine
Hypothalamic releasing hormone that inhibits release of PRL
CRH
Hypothalamic releasing hormone that stimulates release of ACTH, alpha-MSH, and beta-endorphin
GHRH
Hypothalamic releasing hormone that stimulates release of GH
pulsatile
the hypothalamic releasing hormones and the anterior pituitary hormones they control are released in a ______ fashion to maintain target cell sensitivity to them
night
there is a circadian rhythm to the release of anterior pituitary hormones such that the most hormone is released when?
glucocorticoids
________ suppress ACTH and CRH through a negative feedback mechanism
estrogen
in the follicular phase of the menstrual cycle, ______ suppresses both LH and GnRH release
long
A hormone produced by the target organ inhibits the release of the trophic hormone. This is known as _____ loop feedback.
short
A pituitary hormones directly feeds back to its releasing hormone in the hypothalamus. This is the definition of _____ loop feedback
ultrashort
The ability of some hypothalamic releasing hormones to directly inhibit their own further release is known as ______ loop feedback.
ultrashort
The secretion of GnRH and SST is regulated by _____loop feedback
itself, TSH, GH
SST inhibits the release of
TRH, TSH
T3 inhibits the release of
CRH, ACTH
cortisol inhibits the release of
GHRH and GH
IGF-1 inhibits the release of
SST
IGF-1 promotes the release of
dopamine
prolactin promotes the release of
prolactin
dopamine inhibits the release of
itself
GnRH inhibits the release of
GnRH, FSH, LH
Androgens inhibit the release of
GnRH, FSH, LH
in the follicular phase, estrogens inhibit the release of
GnRH
in the ovulatory phase, estrogens inhibit the release of
GnRH, FSH, LH
in the luteal phase, progestins inhibit the release of
both
Addison's disease can be caused by high or low levels of ACTH?
yes
Will patients with Addison's disease caused by a problem with the adrenal cortex be hyperpigmented?
no
Will patients with Addison's disease caused by a problem in the pituitary or hypothalamus be hyperpigmented?
preproopiomelanocortin
ACTH, alpha-MSH, and beta-endorphin are made from a large precursor (with an equally large name) called ___________
free
Only ionized or "_____" calcium is metabolically active and regulated
PTH (parathyroid hormone)
the hormone responsible for minute to minute regulation of calcium levels in the blood
Vitamin D
the molecule that "fights" the long-term battle for calcium homeostasis and is slower acting than PTH
no
can the kidney reabsorb 100% of calcium with maximal stimulation by PTH?
bone
the short-term defense against hypocalcemia is ____-based
gut, dietary
the long-term defense against hypocalcemia is at the level of the ___ and ____ calcium to replace or exceed obligatory losses from other sites of the body
vitamin D
_________ modulates the transcription of PTH through a 5' regulatory element in the PTH gene
parathyroid
the secretion of PTH is exquisitely sensitive to the blood levels of calcium bathing ____ cells
ionized calcium
the major regulator of PTH secretion
no
can total shutdown of PTH release ever be achieved?
increase
low Ca++ levels at the parathyroid cell membrane will increase or decrease PTH secretion?
G protein
the detection of calcium levels by the parathyroid cell is performed by a novel Ca++-sensing seven-membrane-spanning _____ - coupled receptor present on the cell surface.
7
the PTH receptor is a classic G protein-linked receptor with a bundle of _____(#) membrane spanning helices.
1
the subtype of PTH receptor present on the main target organs for PTH action (kidney and bone) is the PTH type-___ receptor
cAMP
the traditional PTH receptor type-1 2nd messenger, although it is also coupled to the IP3 pathway
II
the PTH receptor is a member of a sub-family of G-linked receptors (class ___) which includes the receptors for calcitonin, secretin, GHRH, vasoactive intestinal polypeptide, and others.
osteoblast
PTH's action in bone is primarily on what cell, allowing low doses of PTH to be used to treat osteoporosis
reabsorption, excretion
PTH has a powerful action on the kidney to stimulate calcium ______ and promote inorganic phosphorous (Pi) ______
cAMP
the PTH response in the kidney is linked to what second messenger with such an exuberant response that it spills out of cell and into the urine?
proximal, distal convoluted tubules
the action of PTH in the kidney is most pronounced where?
25-hydroxy vitamin D
PTH activates the 1alpha-hydroxylase which acts on _________ to make fully active 1alpha, 25-dihidroxy vitamin D
1/3
All the structural features necessary for full bioactivity of PTH are present in the amino terminal ______ of the 84 amino acid native hormone. N-terminal truncation thus produces antagonists effective in vivo.
vitamin D
A vitamin that is not a vitamin but a hormone
1alpha, 25-dihydroxy
the fully active, highly potent form of vitamin D
calbindin
the action of vitamin D stimulates calcium transport from the gut lumen to the bloodstream via a calcium-binding protein called ______
hypocalcemia
the symptoms and signs of ______ include tetany, paresthesias, seizures, a Chvostek sign, a Trousseau sign, and calcium deposition in the basal ganglia (visible on skull radiographs)
hypoparathyroidism
characterized by low blood levels of calcium and high phosphate. Most common cause is complications of posterior neck surgery.
hypomagnesemia
causes decreased secretion of PTH plus resistance to PTH action at target organ ("functional" hypoparathyroidism")
pseudohypoparathyroidism
causes low blood calcium and high "Pi" with no deficiency of PTH
Gs
Pseudohypoparathyroidism is genetic and in the most common form, the amount of __ is reduced by half.
osteodystrophy
Many patients with pseudohypoparathyroidism display Albright's hereditary ________, characterized by brachydactyly of 4th & 5th metacarpals and metatarsals.
pseudopseudohypoparathyroidism
Albright's hereditary osteodystrophy without the mineral metabolism disorder
life-threatening
The treatment of hypocalcemia includes the infusion of calcium for ________ hypocalcemia
vitamin D
The treatment of hypocalcemia includes administration of oral calcium and _____ supplements.
kidney stones
In treating hypocalcemia, one should be careful not to overtreat so as to prevent hypercalcuria and ______ due to the absence of PTH-promoted calcium reabsorption in the renal tubule.
7-dehydrocholesterol
Concerning Vitamin D synthesis: ________ is converted to cholecalciferol (vitamin D3), and this requires UV light
cholecalciferol (vitamin D3)
Concerning Vitamin D synthesis: dietary _______ from dairy products can be metabolized into vitamin D
ergocalciferol
Concerning Vitamin D synthesis: _______ from plant sources can be metabolized into vitamin D
25-hydroxy
Concerning Vitamin D synthesis: 25-hydroxylation in the liver forms the principle circulating form of the hormone, ________ vitamin D
proximal tubule
Concerning Vitamin D synthesis: 25-hydroxy vitamin D is 1alpha-hydroxylated in the ____________ of the kidney to form the most potent form of vitamin D.
PTH
the final activation step of vitamin D is dependent on and tightly regulated by ______
macrophages, lymphocytes
in addition to the proximal tubules, 1alpha hydroxylase is also present in activated ______ and ______
sarcoidosis
unregulated hydroxylation of Vitamin D by activated macrophages and lymphocytes can result in hypercalcemia in __________
15-20 days
half-life of 25-dihydroxy vitamin D
12-15 hours
half-life of 1alpha, 25-hydroxy vitamin D
rickets
deficiency of vitamin D in children causes _______
osteomalacia
deficiency of vitamin D in adults causes _______
C
calcitonin (CT) is produced by the perifollicular or __-cells of the thyroid gland
T
T/F there are no sequelae on calcium metabolism from removal of the thyroid gland (site of biosynthesis of CT)
phosphate
CT promotes renal excretion of inorganic ______ similar to PTH
PTH
like ____, CT acts via cAMP and activates the IP3 pathway
CT
____ serves as a tumor marker for medullary carcinoma of thyroid
osteoclasts
calcitonin (CT) lowers serum calcium via its receptors on ________
hypercalcemia
hyperthyroidism increases bone turnover, but the balance favors bone resorption. Hyperthyroidism rarely can produce ________
resorption
excess cortisol leads to bone (formation/resorption)
yes (it is required for bone formation)
does inadequate cortisol lead to any problems with bone formation?
resorption
immobilization causes bone (deposition/resorption)
hypercalcemia
immobilization in a growing child or young adult can lead to _____
resorption
acid promotes bone (resorption / deposition)
liver, kidney
failure of what two organs disrupts metabolism and formation of vitamin D?
GI
pathways to hypercalcemia: increased ___ absorption of calcium
urinary
pathways to hypercalcemia: decreased ____ calcium excretion
increased
pathways to hypercalcemia: (increased / decreased) bone resorption
hypercalcemia
CNS symptoms of _______ include lethargy, depression, stupor, coma, ataxia, psychosis
hypertonia
in the neuromuscular realm, hypercalcemia results in weakness and (hypo/hypertonia)
QT
cardiovascular signs of hypercalcemia include hypertension, bradycardia, asystole, and a shortened ___ interval on EKG
keratopathy
band ____ is seen in the eye with chronic hypercalcemia
stones
in the kidney, hypercalcemia gives rise to ____, polyuria, and nephrocalcinosis
anorexia
the GI symptoms of hypercalcemia include nausea, vomiting, constipation, and _______ (eating disorder)
metastatic calcification
high and prolonged hypercalcemia can lead to ___________ of soft tissues
hypercalcemia (permits renal calcium wasting)
the homeostatic defense against ______ is suppression of PTH secretion by the parathyroid glands
hyperparathyroidism
An elevated PTH in a hypercalcemic patient with no other clinical problems is virtually diagnostic of __________
malignancy
In ________-associated hypercalcemia, PTH levels are suppressed.
PTH
possible mechanisms responsible for hypocalcemia: failure to secrete ___ or resistance to its action
1alpha, 25-dihydroxy vitamin D
possible mechanisms responsible for hypocalcemia: deficiency, failure to produce, or resistance to _____________ (not PTH)
calcium
possible mechanisms responsible for hypocalcemia: overwhelming and rapid complexation or tissue deposition of ______
cortisol
the glucocorticoid produced by the adrenal cortex
aldosterone
the mineralocorticoid produced by the adrenal cortex
catecholamines
the adrenal medulla produces
zona glomerulosa
the outer zone of the adrenal cortex
zona fasciculata
the middle zone of the adrenal cortex
zona reticularis
the inner zone of the adrenal cortex
cortisol
the zona glomerulosa (outer zone) of the adrenal cortex produces this
cortisol
the zona fasciculata (middle zone) of the adrenal cortex produces this
androgens
the zona reticularis (inner zone) of the adrenal cortex produces
1 hr
the half life of cortisol is _______
40 mins
the half life of aldosterone is _____
liver, kidneys
cortisol and aldosterone can be glucuronidated in the ______ and _____, allowing the more hydrophilic version to be excreted in urine and bile
steroid
liver disease is commonly associated with elevated levels of _____ hormones
sulfated
cortisol can also be ______ in the liver and kidneys prior to excretion
transcortin
most circulating cortisol is bound to _____, a protein made by the liver
F (late at night)
T/F cortisol secretion shows a circadian rhythmicity with peak production occuring in the afternoon
cortisol
several enzymes in the liver responsible for the degradation of amino acids and gluconeogenesis are synthesized more rapidly in the presence of _____
insulin
glucocorticoids cause muscle protein catabolism only if _____ levels are low
epinephrine
cortisol will increase the sensitivity of the liver, heart, and fat cells to ________
glucagon
cortisol increases the sensitivity of the liver to ______ (not epinephrine)
cAMP
cortisol increases the sensitivity of certain organs to epinephrine and glucagon by amplifying the amount of ______
inhibits
cortisol (activates / inhibits) the immune response
prostaglandin
cortisol decreases transcription of the gene for phospholipase A2 thereby disrupting ______ production which is a key component of inflammation responses
surfactant
cortisol is required for the production of _____ in the lung
MSH
excessive production of ACTH will also cause skin darkening because its precursor also contains the the sequence for _____
stress
neural input to the CRH-producing cells result in CRH secretion in response to physical or emotional _______
cAMP, Ca
the second messenger(s) utilized by ACTH
Cushing's
disease caused by overproduction of glucocorticoids characterized by hyperglycemia, hypertension, muscle wasting, and reduced immune function
Na, K
aldosterone causes ______ retention and _____ excretion by the kidneys
luminal, basolateral
aldosterone increases the transcription of a sodium ion permease at the ______ cell surface and the Na+/K+ at the _____ surface
angiotensin II, III
the primary stimulus for aldosterone production is ____________
atrial natiuretic hormone
the polypeptide hormone produced in the atria and released in response to stretch. it increases the excretion of sodium and water
cretinism
lack of thyroid hormones early in life results in permanent mental retardation called ________
thyroid
nearly the entire daily requirement for iodine (100 micrograms) is for the production of ______ hormones
thyroid peroxidase
the enzyme that oxidizes I- to its highly reactive free radical form in the thyroid
tyrosine
the amino acid to which iodine is bound in thyroglobulin
most
(no, little, some, most, all) circulating T3 is derived from peripheral deiodination of T4 in skeletal muscle, liver, and kidney
reverse (rT3)
T4 can be peripherally deiodinated to form the inactive _________ T3.
falls
the ratio of T3/rT3 (rises/falls) during prolonged starvation
T3 (ten-fold more)
does T3 or T4 bind more tightly to the thyroid hormone receptor
beta
the biological activity of TSH is in which subunit?
cAMP
TSH acts through what second messenger?
TSH
_____ stimulates all aspects of thyroid hormone synthesis and secretion
lowered
The release of TRH from the hypothalamus occurs in response to a variety of stimuli including (raised/lowered) body temperature
TRH
T3 both inhibits the release of and reduces the TSH-secreting pituitary cells' sensitivity to _______
steroid
thyroid hormone receptors are members of the ______ hormone receptor superfamily
globulin
most thyroid hormones circulate bound to thyroid binding _____ which is produced by the liver
brain, spleen, testes/ovaries
the only tissues that do not respond to T3 by increasing metabolic rate
T3
___ causes increased metabolism by increasing transcription of oxidative phosphorylation genes, activation of the Na+/K+ pump, and increased turnover of cellular constituents
degradation
T3 stimulates protein turnover, but its effect on (production/degradation) is more dramatic
heart, liver, adipose
T3 increases the sensitivities of ____,_____, and _____ tissue to epinephrine by increasing transcription of beta adrenergic receptors
hypertension
in hyperthyroidism, _____ results in part from the increased beta adrenergic receptors in cardiac muscle and smooth muscle cells
axons, dendrites
T3 is required for the proper growth of ___ and ____ and for the proper myelination of neurons.
Graves'
the most common cause of hyperthyroidism in the US
hyperthyroidism
the symptoms of _______, whatever its cause are skeletal muscle weakness, weight loss, increased sweating, heat intolerance, hyperglycemia, and hypertension
Hashimoto's
hypothyroidism is most often due to an autoimmune destruction of the thyroid called ______ disease
hypothyroidism
the symptoms of _____ include weight gain, tiredness, hypoglycemia, and hypotension. Also, dry, rough skin and puffy appearance.
goiter
hypothyroidism due to lack of iodine in the diet can result in ____ in the neck.
80, 110
the normal range of plasma glucose levels is ___-___ mg/dl
brain, renal medulla, intestinal mucosa, WBC, RBC
glucose-requiring tissues (5)
insulin
A polypeptide hormone secreted by the beta cells of the pancreatic islets of Langerhans
pre-proinsulin
insulin is synthesized as _____
ER
the pre-sequence of pre-proinsulin is cleaved where?
secretory granules
proinsulin is processed within the ________ of the beta cells to 2 separate polypeptide chains held together by disulfide bonds
C
circulating levels of ___-peptide are an indication of endogenous insulin production
plasma glucose conc
the major regulator of insulin synthesis and secretion
vesicles
secretion of insulin involves an initial rapid burst corresponding to fusion of previously formed ______ with the plasma membrane, followed by a slower, sustained release that lasts for as long as excess glucose is present
AAs, GIP (gastric inhibitory peptide), vagus
aside from glucose, name three other important stimulators of insulin secretion
SST
insulin secretion is inhibited by
GLUT4
insulin causes rapid insertion of _____ glucose transporters into the plasma membrane
amino acids
insulin stimulates active transport of _____ (not glucose) into skeletal muscle, cardiac muscle, adipocytes, and fibroblasts
glucose
insulin stimulates active transport of _____ into skeletal muscle, cardiac muscle, adipocytes, and fibroblasts
dec, inc, inc
in the liver, insulin (inc/ dec) glucose production, (inc/dec) triglyceride synthesis, (inc/dec) lipogenesis
inc, inc, dec
insulin (inc/dec) fat production, and (inc/dec) lipoprotein lipase activity in capillary wall, and (inc/dec) trigylceride breakdown in adipose tissue
alpha, beta
insulin binds to the ____ subunit of the insulin receptor and stimulates the tyrosine kinase activity of the ____ subunit
phospholipase C
insulin binding to its receptor also activates what enzyme other than the tyrosine kinase?
glucagon
insulin reduces cAMP in the liver only if cAMP has been previously elevated by exposure to _________
elevated
in response to (elevated/decreased) insulin levels, target tissues decrease insulin receptor numbers through endocytosis and lysosomal degradation
glucagon
a single chain polypeptide hormone produced in the alpha cells of the pancreatic islets of Langerhans
both
with a high protein meal, which will be elevated, insulin or glucagon?
promotes, inhibits
epinephrine (promotes/inhibits) and SST (promotes/inhibits) glucagon release
liver
the only target tissue of glucagon
cAMP, Ca
glucagon's second messengers
stimulates
exercise (stimulates/inhibits) all actions of insulin
1
the type of diabetes that is an autoimmune disease in which Abs destroy the beta cells in the islets of Langerhans
1
the type of diabetes characterized by a lack of endogenous insulin production
1
the type of diabetes also known as insulin-dependent diabetes mellitus
2
the type of diabetes also known as noninsulin-dependent
1
the type of diabetes with a SMALL genetic component
2
the type of diabetes that typically begins after age 40
2
the type of diabetes caused by target tissue resistance to insulin
2
part of the cause of type ___ diabetes is down regulation of insulin receptors in target tissues
less
adipose tissue is (more/less) insulin resistant than is liver and muscle, which contributes to the obesity that is associated with type 2 diabetes
2
the type of diabetes with a LARGE genetic component
energy intake
the first law of thermodynamics: _________ = internal heat + work + energy stored
BMR (basal metabolic rate)
The metabolic rate of a resting fasting and nonstressed endotherm
2000
The BMR for a 70 kg man (kcal/day)
1300
The BMR for a 50 kg woman (kcal/day)
4.8
one L of O2 gas consumed equals how many calories of ATP generated?
CO2 produced, O2 consumed
the respiratory quotient (RQ) is _____ divided by ______
1
RQ for carbohydrate
lower
The RQ of lipids and proteins is lower or higher than that for carbs?
lipid, ethanol
the top 2 most efficient energy sources
leptin
fat cells release hormones such as _____ that suppress appetite
1
blood contains 20 g of free glucose, enough to supply calories at the BMR for how many hours?
100
how many grams of glycogen are stored in the liver (glycogen that can be converted into blood glucose)
3
how many kg of protein can be metabolized by a 70 kg man in starvation before the amount lost is life-threatening?
450 g
how many g of protein would provide the 2000 cals per day required for BMR?
250 g
how many g of triglyceride would provide the 2000 cals per day required for BMR?
beta-hydroxybutyrate, acetoacetate, acetone
the ketone bodies converted from the acetyl CoA produced from lipid breakdown
same
does the amount of glucagon in the blood after a meal inc/dec/same?
inc
in early and prolonged fasting, blood levels of catecholamines inc/dec?
inc
in early and prolonged fasting, blood levels of GH inc/dec?
inc
in early and prolonged fasting, blood levels of glucocorticoids inc/dec?
dec, inc
in prolonged fasting, blood levels of T3 inc/dec? rT3?
inc, inc, dec, dec, inc, dec, inc, dec
insulin's effects in liver (inc/dec?): glycogen synthesis, glycolysis, glycogenolysis, gluconeogenesis, lipogenesis, lipolysis, protein synthesis, protein degradation
inc, inc, inc, inc, dec, dec, inc
insulin's effects in skeletal and cardiac muscle (inc/dec?): glucose uptake, glycolysis, amino acid uptake, protein synthesis, glycogen breakdown, protein degradation, potassium uptake
inc, inc, inc, inc, inc, dec, inc, dec
insulin's effects in adipose tissue (inc/dec?): glucose uptake, fatty acid synthesis, lipid uptake, glycolysis, lipoprotein lipase activity, hormone-sensitive lipase activity, lipogenesis, lipolysis
acidosis
prolonged starvation can cause metabolic ____ (because of what the 1st two ketone bodies are)
type 1 diabetic
an extreme example of the metabolic changes due to long-term starvation is the untreated ____________
no
is blood flow to the brain changed by exercise?
yes (reduced)
is blood flow to the kidneys changed by exercise?
white (type IIB)
anaerobic exercise using ATP & phosphocreatine within the exercising muscle utilizes ____ muscle fibers
red (type I)
sustained aerobic exercise uses ___ muscle fibers
white, red, red, red, red, white
which muscle type, white or red, as the most of the following: anaeorbic metabolism, slow contraction time, myoglobin, mitochondria, capillaries, glycogen
dec, inc, inc, inc, inc
endocrine changes with exercise (inc/dec?): insulin, glucagon, epinephrine, cortisol, GH
SRY
the ____ gene on the short arm of the Y chromosomes is the key determinant for testicular differentiation
TDF (testicular differentiation factor)
the SRY gene encodes _____
HMG (high mobility group)
TDF is a transcription factor of the ______ superfamily
CG (chorionic gonadotropin)
the hormone similar to LH which stimulates fetal Leydig cells to produce testosterone
DHT (dihydrotestosterone)
certain male reproductive structures such as the prostate, penis, urethra, and scrotum require conversion of testosterone to _____
MIF (Mullerian Inhibiting Factor)
Sertoli cells produce _______ which causes regression of the Mullerian duct
7
the descent of the testes to the scrotum occurs in what month of gestation?
androgens
__________ affect the hypothalamus to prevent the cyclical release of pituitary hormones, generating the menstrual cycle
Leydig
what cells lie between the seminiferous tubules (in the interstitium)
spermatogonia (immature), spermatozoa (mature)
in the seminiferous tubules, ________ are located near the periphery and _______ near the lumen
GnRH
_________ stimulates the release of LH and FSH while inhibiting its own production
estrogens
androgens can be converted to _____ in sertoli cells and peripherally
estrogens
_______ have effects on fertility and bone physiology in the male and also regulate GnRH release by the hypothalamus
ABP (androgen binding protein)
a protein that binds testosterone secreted by sertoli cells into the lumen to keep keep luminal testosterone levels high
P-450 aromatase
____ produced within the sertoli cell converts testosterone from Leydig cells into estradiol
growth factors
________ released by sertoli cells increase the number of spermatogonia and make Leydig cells more sensitive to LH
inhibins, activins
_____ and _______ are gonadal peptides that play important roles in regulation of the anterior pituitary in both males and females
FSH
inhibins and activins in males function in feedback inhibition of _____ secretion from the anterior pituitary
adrenals
some testosterone in males is derived from what glands (not testes)
sex steroid binding
most testosterone in the blood of males is bound to varous ________ proteins made by the liver
17-ketosteroids
the degradation products of testosterone
5-alpha_reductase
testosterone is turned into DHT by what enzyme?
30-50
DHT is how many times more biologically active than testosterone?
estradiol
in the brain, the effects of testosterone are mediated after it is converted to _______
testosterone, prolactin
______ and ______ act synergistically to regulate the process of the prostate sending epithelial ductal branches into its surrounding stroma
BPH (benign prostatic hyperplasia)
overproliferation of the prostate produces _________
less
before puberty, the hypothalamus and pituitary become (more or less) sensitive to feedback inhibition by testosterone?
primordial germ cells
spermatogonia are derived from _____ that migrate to the testis during embryogenesis
primary spermatocytes (4N)
spermatogonia that enter into their first meiotic division, and their (chromosome number)
secondary spermatocytes (2N)
daughter cells of primary spermatocytes that have just completed their first meiotic division
spermatids (1N)
germ cells in male that have just fully completed meiosis
spermiogenesis
spermatids develop into spermatozoa through a process known as __________
74
the time it takes for spermatogonia to become spermatozoa (days)
rete testes
the seminiferous tubules empty into the _____, a network of tubules that serves as a reservoir for sperm
efferent ductules
the rete testes is connected to the epididymis via the ___________
ciliary
transfer of sperm to the rete testes and epididymis occurs passively with help from the _____ action of luminal epithelial cells
motility
maturation of sperm in the epididymis includes progressive increase in sperm ______
acrosome
maturation of sperm in the epididymis includes maturation of sperm ______
plasma membrane
maturation of sperm in the epididymis includes molecular reorganization of the _______
zona pellucida
maturation of sperm in the epididymis includes ability to bind ______
disulfide
maturation of sperm in the epididymis includes increased ______ bonding of sperm nucleoproteins
glycosidic
maturation of sperm in the epididymis includes topographical regionalization of _______ residues
decreased
maturation of sperm in the epididymis includes ________ cytoplasm and cell volumes
seminal vesicles
approximately 60% of the volume of semen is from the _________
NO
during erection, release of ____ at parasympathetic postganglionic terminals causes vascular smooth cells to produce cGMP which causes vasodilation
cGMP
Sildenafil (Viagra) inhibits breakdown of ______ by inhibiting a specific phosphodiesterase (type 5)
sympathetic
male emission is primarily under _______ control, whereas ejactulation is a reflex triggered by the entry of semen from the proximal urethra into the bulbous urethra
PRL
___ potentiates the stimulatory effect of LH on testosterone synthesis
GnRH, FSH, LH
hyperprolactemia leads to testicular atrophy and infertility due to PRL inhibiting prodcution of ______, ____, and____
estrogens
activins in females increase FSH mRNA levels and stimulate synthesis of _______ by ovaries
androgens
inhibins in females decrease FSH mRNA levels and stimulate _____ production within the ovary
arcuate nucleus
neurons in the _____ of hypothalamus in females are responsible for the pulsatile hourly release of GnRH
preoptic area
neurons in the _____ of hypothalamus in females are responsible for the monthly midcycle increase in GnRH that leads to the LH surge that triggers ovulation
both, high
(low/high/both) plasma concentrations of estrogens inhibit LH and FSH release; (low/high/both) concentrations of progestins inhibit FSH and LH release
opiates
inhibitory neurons in the arcuate nucleaus exert their effects via ______
GABA
inhibitory neurons in preoptic area exert their effects via ______
2
in the menstrual cycle, the switch from negative to positive feedback requires a "threshold" level of estrogen for ___ days
ovary, adrenal gland, adipose
estrogens in females are made in what 3 organs?
17-alpha-hydroxyprogesterone
the two major progestins are progesterone and _________
CL (corpus luteum)
where are estrogens synthesized in females during the luteal phase?
androstenedione
the theca cells take up LDL cholesterol and produce _____
aromatase
granulosa cells have _____ to produce estradiol from androgens but lack 17-alpha-hydroxylase and 17,20 desmolase necessary for making androgens
cAMP
LH stimulates theca cells via what pathway?
androstenedione
theca cells synthesize what when stimulated by LH?
cAMP
FSH acting via the ______ pathway stimulates the granulosa cell to produce aromatase
estrone
aromatase in granulosa cells converts androstenedione to _____
estradiol
17-beta-hydroxysteroid dehydrogenase (17-beta-HSD) in granulosa cells converts estrone to ___
testosterone
17-beta-HSD can convert androstenedione to _____ and then aromatase can convert this to estradiol
granulosa-lutein
the increased progesterone biosynthesis in the midluteal phase is due to invasion of blood vessels toward the ________ cells
progesterone
the major products of the corpus luteum are progesterone, 17-alpha-hydroxyprogesterone, and some estradiol. which can be made directly the granulosa-lutein cell?
2
what percent of plasma estradiol and testosterone is free in the circulation?
nucleus
estrogen receptors are located where in the cell
glandular
progesterone and other progestins stimulate _____ secretion in reproductive tissues and promote the maturation of certain estrogen-stimulated tissues.
TGF-beta (transforming growth factor beta)
inhibins and activins belong to the _____ supergene family
granulosa
inhibins are produced by what cells of the follicle?
primary oocytes
cells in the ovary arrested in prophase of meiosis I at birth are called
1-2
number of primary oocytes at birth: ___ million
400,000
number or primary oocytes at puberty: ______
primordial follicles
primary follicles surrounded by a single layer of spindle-shaped pregranulosa cells coated by a basal lamina
follicle
the primary functional unit of the ovary
16
the first primordial follicle appears ___ weeks into intrauterine life
6
generation of primordial follicles is complete about __ months after birth
primordial, primary, secondary
which follicles are solid masses of cells that lack an antrum
tertiary, graafian
which follicles have a fluid-filled "antrum"
secondary
follicles characterized by multiple layers of granulosa cells and stroma-derived theca cells surrounding the basement membrane
tertiary
follicles with an antrum and with secretion of fluid by granulosa cells. now apparent are multiple layers of both theca and granulosa cells, connected by gap junctions
gap
___ junctions exist between granulosa cells and the oocyte
graafian
follicle in which antrum encircles the oocyte except for a small cumulus that attaches the oocyte to the rest of the follicle
mural
granulosa cells farthest from the center of the graafian follicle - they are the most metabolically active
cumulus
granulosa cells that are shed with the oocyte at the time of ovulation. they cannot generate estrogens
antral
granulosa cells that face the antrum of the graafian follicle and become the large luteal cells of the corpus luteum
24-36
the LH surge is initiated how many hours after peak estradiol secretion by the dominant follicle
12
ovulation occurs how many hours after LH surge peak
secondary oocyte
during the LH surge, the oocyte resumes meiosis and completes its first meiotic division hours before ovulation, producing a polar body and a _______
fertilization
the secondary oocyte begins its second meiotic division but is arrested in metaphase until _______
ampullary
fertilization, if it occurs, takes place in the ____ portion of the fallopian tube
72
after fertilization, the zygote chills in the ampulla for ___ hrs before being whisked to the uterine cavity
2-3
the zygote floats free in the uterine cavity for ___ days before implanting to the wall
hCG (chorionic gonadotropin)
the corpus luteum is maintained by _____ produced by the developing conceptus (embryo)
9
the CL degrades at about week __ of gestation, when placental function is well established
1
the beginning of tissue breakdown and bleeding in the menstrual phase happens on what day of the menstrual cycle?
5
after menstruation the endometrium is restored by about day ___ of the cycle
stromal
restoration of the endometrium occurs due to proliferation of basal ___ cells on the denuded surface of the uterus (the zona basalis) as well as proliferation of epithelial cells from other parts of the uterus
3
increased growth of the stromal and glandular epithelium of the uterus continues through the follicular phase until about ___ days after ovulation
IGFs (insulin-like growth factors), TGFs (transforming growth factors), EGF (epidermal growth factor)
estrogens induce the synthesis of growth factors, autocrine and paracrine mediators required for growth and maturation of the endometrium (name 3 examples)
stroma
progesterone inhibits epithelial cell proliferation but promotes proliferation of the endometrial ___
antiestrogen
progesterone exerts its ____ effects by stimulating 17B-HSD and sulfotransferase, enzymes that convert estradiol to weaker estrogens
estrone
17B-HSD converts estradiol to ___ (weaker form, thanks to progesterone)
estradiol 3-sulfate
sulfotransferase conjugates estrogens with sulfate to produce derivatives such as ____ to make it weaker
glycogen
the middle to late secretory phase is characterized by increased vascularization and ___ content of the endometrium
decidiual
stromal cells that surround the spiral arteries develop into ____ cells
zona compacta
upper layer of the endometrium (together with zona spongiosa, makes up functional layer of the endometrium)
zona spongiosa
middle level of the endometrium
fibrolysins
menstrual blood does not clot because of the presence of ____ released from the necrotic endometrial tissue
parasympathetic
much of the response in the excitement stage of female sex is due to stimulation by _____ fibers
cerebrum
psychic stimuli during female sex are coordinated by the ____ which causes a generalized tension throughout the body and modulates the autonomic response
spinal cord
orgasm is coordinated in women through a ____ reflex
5
the sperm reach the ampulla of the fallopian tube how many minutes after ejaculation?
SERMS (selective estrogen receptor modulators)
a group of structurally dissimilar compounds that interact with estrogen receptors
reproductive
tamoxifen and relaxifene are SERMS with beneficial effects on bone and the CV system, but antagonize estrogen in ____ tissues.
pronuclei
fusion of the male and female _____ mark the end of fertilization
morula
the zygote remains in the fallopian tubes for 3 days and develops into a
12
at the morula stage, the zygote is a solid mass of ___ or more cells
blastocyst
when the morula is floating freely in the uterine cavity, it transforms into a ball-like structure with a fluid-filled cavity called a _____
trophoblast
surrounding the inner cavity of the blastocyst is a thin layer of trophoectoderm cells that forms the _____
amnion, yolk sac, placenta
the trophoblast will develop into a variety of supporting structures including the ______ , ____, and fetal portion of the ______
inner cell mass
one side of the cavity of the blastocyst, attached to the trophoblast, is an ____________ which develops into the embryo proper
6, 7
implantation of the human blastocyst normally occurs __ to __ days after ovulation
predecidualization
the process in which stromal cells of the endometrium transform into rounded decidiual cells, spreading across the surface to make it more compact and separating it from the deeper spongy layer
7
engorgement of the endometrium driver by CL progesterone peaks ___ days after ovulation
9, 10
predecidualization occurs __ to __ days after ovulation
decidua
the specialized endometrium of pregnancy
decidua basalis
the area of endometrium underneath the implanting embryo
decidua capsularis
the area of endometrium which overlies the embryo
decidua parietalis
the area of endometrium which overs the remaining uterine surface
hCG
_____ secreted by blastocyst has immunosuppresive activity, has growth-promoting activity, and acts as an autocrine growth factor that promotes trophoblast growth and placental development
hatching
the process of degeneration of the zona pellucida surrounding the blastocyst using plasmin and other lytic factors in the endometrium
apposition, adhesion, invasion
the three stages of implantation
apposition
the first contact between the blastocyst wall and the endometrial epithelium
integrin
adhesion of the trophoblast to the uterine epithelium is thought to involve the ____ family of receptors
laminin, fibronectin
integrins on the trophoblast are thought to bind initially to _______ distributed around the decidual cells of the endometrium and later to ______ in the basement membrane
cytotrophoblast
as the blastocyst attaches to the epithelium, the trophoblast differentiates into 2 layers, an inner ________ and an outer syncytiotrophoblast
syncytiotrophoblast
a multinucleated mass outside the cytotrophoblast without cellular boundaries
TNF-alpha (tumor necrosis factor alpha)
the syncytiotrophoblast secretes______ to interfere with the expression of cadherins and beta-catenin to penetrate the basement membrane and ultimately reach the uterine stroma
lacunae
as the syncytiotrophoblast invades the endometrium, fluid-filled holes called _____ develop within the syncytium 8-9 days after fertilization
primary chorionic villi
within 15 days after fertilization, some cytotrophoblasts invade the syncytiotrophoblast, forming finger-like projections called _______
secondary chorionic villi
as the placenta develops further, mesenchymal cells from the extraembryonic mesoderm invade the primary chorionic villi, which are now known as _______
tertiary chorionic villi
eventually, the mesenchymal cells form fetal blood vessels de novo, at which point the villi are known as ________
umbilical
the fetal blood originates from two _______ arteries
umbilical vein
blood with high O2 and nutrient content returns to the fetus through a single ______
kidneys, lungs
the two major sources of amniotic fluid production
cardiac output
the relatively high ____ per unit body weight of the fetus ensures adequate fetal oxygenation
1.5
fetal blood late in pregnancy has an Hb concentration how many times higher than that of an adult?
facilitated diffusion
glucose is shuttled from mother to fetus through _____
secondary active
amino acids move from mother to fetus by _______ transport
releasing
the placenta produces placental variants of all known ______ hormones
hCS1, hCS2
the two human chorionic somatomammotropins (aka human placental lactogen - hPL)
estriol
a major estrogen during pregnancy
LDL
cholesterol is contributed to the placenta in the form of ____ cholesterol
adrenal glands, liver
the two critical enzymes lacking in the placenta for the formation of esterone and estradiol (17-alpha-hydroxylase and 17,20 desmolase) are contributed by what 2 fetal organs?
adrenal glands, liver
the placenta lacks 16alpha-hydroxylase which is needed to make estriol, and this is supplied by what 2 fetal organs
sulfated
androgens made by the fetus are ____ to reduce their biological activity and prevent masculinization of female fetuses
38 (266 days)
mean duration of pregnancy in weeks from time of ovulation
40 (280 days)
mean duration of pregnancy in weeks from time of last menstrual period
45, 75, 100
maternal blood volume can increase as much as ___% for single births and up to __-__% in twin/triplet pregnancies
plasma, erythrocytes
the total increase in maternal blood volume is due to both ___ and ___
vasodilation
the increase in maternal blood volume is caused by _______ caused by elevated progesterone and estrogens
30
during pregnancy, and additional ___ g of protein are needed each day to meet growth demands
iron
____ supplements are recommended during pregnancy because very few women have adequate stores
5
the amount you weight you lose when you break down X grams of proteins is how many times more than the weight of the protein itself?
folate
____ requirements increase during pregnancy primarily because of the increased demand for producing blood cells
11.5, 16
the normal weight gain during pregnancy for a woman with normal weight/height ratio is ___ to ___ kg
relaxin
progesterone and the hormone _____ may promote inactivity of uterus
prostaglandins
_______ made in the uterus, placenta, and fetal membranes are thought to play a key role in the initiation of labor along with oxytocin