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147 terms

Endocrinology

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method of hormone release
pulsatile: especially important in hypothalamus and pituitary
biologically active concentration of hormone
very small; generally nano- to picomolar amounts
characteristics of hormone receptors
high affinity and high specificity
ablation
removal or whole or portion of gland to study the function of the gland
replacement therapy
method of studying gland following ablation; hormones are given to determine the physiological effect of the absence of the gland.
regulation of hormone secretion
a product of hormone action in target cells regulates secretion by a direct mechanism operating in the glandular cells themselves
hypothalamic-hypophyseal system
important in regulation of glandular secretion; location of important feedback mechanism
endocrine
glandular cells secrete hormone directly to blood
neuroendocrine
neuron secretes hormone directly to blood
paracrine
glandular cells secrete hormones into the lumen
neurocrine
secretion of neurotransmitters into synapse
autocrine
secreted hormone acts on releasing cell
Polypeptide hormone biosynthesis and action regulation
transcription, posttranscriptional processing of precursor mRNA, mRNA stability, mRNA export from nucleus to cytoplasm, mRNA translation, Posttranslational processing, polypeptide folding and subunit assembly, degradation, secretion
covalent posttranslational modifications of polypeptide hormones
glycosylation, iodination, sulfation, amidation, acetylation, phosphorylation
insulin
produced by Beta cells in the islets of Langerhans in the pancreas; release stimulated by increase in blood glucose levels
glucagon
produced by alpha cells in the islets of Langerhans in the pancreas; release stimulated by decrease in blood glucose levels
adenohypophysis
anterior pituitary; not innervated!
rathke's pouch
fetal structure; invagination of the oral ectoderm that leads to development of the anterior pituitary
sella turcica
depression in the sphenoid bone that houses the pituitary
pituitary portal system
vascularization of the pituitary; resulting in transfer of hypothalamic secretions to anterior pituitary for regulation
pars distalis
location of most anterior pituitary hormone production
basophil hormones
glycoprotein hormones which are comprised of two chains: alpha subunit is conserved throughout a species, beta subunit confers specificity. Examples include LH, FSH, TSH, ACTH
Luteinizing hormone (LH)
stimulates formation of the corpus luteum and ovulation in female; stimulates testosterone secretion in males
Follicle Stimulating Hormone (FSH)
Stimulates follicular selection and development; upregulates LH receptors; stimulates androgen binding protein (ABP) by Sertoli cells in males
Thyroid Stimulating Hormone (TSH)
stimulates thyroid hormone production T4 and T3
acidophil hormones
protein hormones which show great conservation of structure. Examples include prolactin and growth hormone
prolactin
stimulated mammary development and lactogenesis in female mammals, crop sac and brood patch development in birds, necessary for corpus luteum maintenance in rodents; frequently acts in permissive manner with estrogen, progesterone, glucocorticoids, insulin and growth hormone
Growth Hormone (GH)
responsible for stimulating growth; stimulates gluconeogenesis and is protein anabolic. Effects are mediated both directly and indirectly through somatomedins produced in response to GH. Release is increased by hypoglycemia and sleep
Adrenocorticotropic hormone (ACTH)
protein hormone that acts on andrenal cortex to stimulate steroid production (mainly glucocorticoids, but also some mineralocorticoids)
POMC
important steriod precursor molecule; BIG! found in posterior, intermediate and anterior pituitary. released early in the morning. precursor to ACTH and endorphins
MSH
controls melanin pigmentation in most vertebrates
beta-lipotropin
stimulates lipolysis in adipose
endorphins
endogenous opiate-like molecules
pars intermedia
area between anterior and posterior pituitary
significance of the neuroendocrine system
enables hypothalamus to act as a neuroendocrine transducer; passes information from CNS to other somatic cells
Gonadotropin releasing hormone (GnRH)
decapeptide hormone stimulates release of LH, FSH. Release is pulsatile
Thyrotropic releasing hormone (TRH)
tripeptide hormone stimulates release of TSH
Somatotropic Releasing Hormone (SRH)
44 amino acid peptide stimulates release of GH, inhibited by inhibitor hormones, brain and pancreas effects and stress
Prolactin Releasing Factor (PRF)
stimulates release of prolactin
Oxytocin
hormone that stimulates prolactin release, milk letdown in mammary gland, contraction of uterus
Prolactin inhibiting factor (PIF)
inhibits prolactin release; DOPAMINE
Corticotropin releasing hormone (CRH)
41 aa peptide hormone stimulates ACTH release
MIF
MSH release inhibiting factor
neurosecretory neuron
synthesizes and secretes a releasing hormone to be passes to primary plexus (component of the hypothalamus)
hypophysiotropic area
hypothalamus; nourishes pituitary
pars nervosa
posterior pituitary
paraventricular nuclei
structurally and functionally unique nuclei responsible for secretion of hypothalamic hormones
Prolactin regulation
performed by dopamine release (inhibitory)
Neuroendocrine integration of LH release in females
GnRH released in high pulse manner
Neuroendocrine integration of FSH release in females
GnRH released in slow pulse manner
GnRH1
conserved in all mammals; differs in one amino acid in birds
GnRH2
highly conserved in all species; involved more in behavioral processes than in gonadotropin release
effect of estrogen secretion on ovary
upregulation of GnRH receptors
Neuroendocrine integration of LH and FSH release in males
GnRH regulates pituitary release of LH and FSH as dictated by testosterone feedback
GnIH
12 amino acid peptide hormone released to median eminence of pituitary from hypothalamus; increases during non-breeding season
location of melatonin production
pineal gland and brain in mammals
neuroendocrine integration of TSH release
Stimulation from limbic structures and preoptic area stimultes hypothalamus which releases TRH into portal system and stimulates TSH release from pars distalis; T3 and T4 feedback to hypothalamus to dictate further release
neuroendocrine integration of GH release
GHRH and somatostatin released together to regulate GH release; IGF1 feeds back to hypothalamus
Ghrelin
produced by the stomach when hungry
Neuroendocrine regulation of ACTH release
CRH and vasopressin act on anterior pituitary to dictate release; glucocorticoids feedback on hypothalamus
neurohemal organ
posterior pituitary; storage area where products of neurons are released to the bloodstream
posterior pituitary hormones
oxytocin and vasopressin (ADH)
magnocellular neurons of hypothalamus
paraventricular nuclei; supraoptic nuclei; synthesize posterior pituitary hormones
site of oxytocin synthesis
paraventricular nuclei of hypothalamus
site of vasopressin synthesis
supraoptic nuclei of hypothalamus
Neurohypophysin 1
oxytocin associated; estrogen stimulated
Neurohypophysin 2
vasopressin associated; nicotine stimulated
stimulus for secretion of posterior pituitary hormones
action potential
vasopressin
regulates extracellular fluid volume; promotes water movement
oxytocin mechanism of action
phospholipase c
vasopressin mechanism of action
receptor linked to adenylate cyclase system; stimulates water retention, works on ascending loop of henle
oxytocin release stimulation
vaginal or nipple stimulation; hemorrhage, stress, estrogen
oxytocin release inhibition
severe pain, increased temperature, loud noise
vasopressin release stimulation
water deprivation, hemorrhage, pain, stress, increased temperature, opiates, nicotine, prostaglandins,angiotensin II
vasopressin release inhibition
decrease in temperature, ethanol, cardiac hormones
neurophysin
associated protein secreted in equimolar amounts with pituitary hormones
V1 receptors
modulate vasoconstriction
V2 receptors
mediate vasopressin at cellular level in kidney
classical endocrine experiment
remove gland, see what happens, give replacement therapy
compensatory hypertrophy
remaining gland gets bigger
bioassay requirements
need not be conspecific
physiological dose
dose of hormone placed experimentally in blood equivalent to that observed in an intact animal
pharmacological dose
unusually high dose of hormone placed experimentally in blood
parabiosis
attachment of the circulatory system of one animal to another animal; used to determine the presence of an endocrine factor
radioimmunoassay principle
set up competitive binding for antibody binding sites between labeled and unlabeled hormones
RIA assumptions
equal binding affinity for labeled and unlabeled hormones
RIA requirements
antibody (steroid or protein hormones); steriod hormone preparation; labeled hormone preparation
ELISA
Enzyme Linked ImmunoSorbent Assay
Steps of an ELISA
apply antibody to well plate; incubate; wash; cover with protein; wash; introduce hormone; wash; treat with marked antibody that will bind to hormone; treat with color producing substrate; color is produced if enzyme is present
northern blot
allows for bioassay via hormone RNA; permits determination of the size of the RNA
northern blot steps
fix tissue sample to slide; apply radiolabeled probe; hybridize; dip into emulsion; wash slides; develop and examine microscopically
reverse transcription steps
isolate RNA, addreverse transcriptase, make cDNA, design primers, go to town
Cell Surface Receptors
characterized by receptor: effector coupling by a G protein
protein/peptide hormone receptors
membrane spanning hormone receptors; single membrane spanning component can be with or without tyrosine kinase; 7 membrane spanning may either be coupled to a G protein or be part of an ion channel
adenylyl cyclase mediating hormones
beta adrenergic, LH, FSH, TSH, hCG, vasopressin, ACTH, vasopressin V2
phosphoinositide turnover mediating hormones
vasopressin V1
tyrosine kinase activation mediating hormones
GH, insulin, Prolactin
Steroid hormone receptors
classically intracellular; hormone passes through cell membrane and acts through a binding cascade to affect transcription
agonist
compound that acts like a hormone and binds to a receptor, activating it
antagonist
compound that binds to a receptor, blocking hormone response
receptor mediated endocytosis
mechanism by which hormone receptors are downregulated
second messenger
intrecellular molecule which carries out a hormones effects intracellularly; does what the hormones does. hormone stimulation increases conc. in cell
membrane receptor activation of adenylate cyclase
hormone binds, alpha subunit activates protein, ATP ultimately converted to cAMP
Activation of protein kinase a
performed by cAMP
cAMP inhibition
performed by alpha inhibitory subunits
adrenergic receptor mode of function
couples with G protein, activates alpha subunit, begins making cAMP, BetaARK phosphorylated BetaAR; deactivating and downregulating the receptor
heterologous desensitization
hormone "pool" lost with processing
Beta arrestin action
immediately desensitizes receptor; but also plays a role in long term mechanisms of extracellularly regulated kinases
phosphodiesterase inhibitors
methylxanthines (caffeine, tea stuff, chocolate stuff): overall result in to increase cAMP prevalence. acts as an endogenous epinephrine boots
protein kinase a function
phosphorylates and activates proteins
Phosphoinositide system
cell surface receptors; G protein linked. phospholipase C activated by PIP2, generating inositol triphosphate and diacylglycerol and activating protein kinase C
role of calmodulin
enhances the activity of protein kinase C
tyrosine kinase activators
generally long range effect hormones; MAPK, mitosis stimulating kinase
tyrosine kinase activity receptors
generally dimers; hormone binding causes conformational change in receptor which confers biological activity
smads
mediate TGFbeta family members
classes of serine, threonine kinase receptors
type 1 and type 2 homodimers and heterodimers
signalling mechanism of receptors with serine threonine kinase receptors
hormone binding to type II receptor, recruitment of type I receptor, phosphorylation of type I receptor. signalling only occurs when receptors are dimerized
smad 4
activation generally associated with transcription
significance of zinc fingers in steroid receptors
allows receptor to interpolate itself into DNA
location of steroid hormone receptors
associated with or in nucleus
gene transcription regulation by steroid receptors
receptor binds hormone, dissociated from complex with heat shock protein, binds upstream to target DNA, recruits coactivators
gene transcription regulation by thyroid receptors
inactive receptor sits on DNA and binds a repressor. Corepressor released following hormone binding and coactivator can be bound
estrogen receptors
classically tethered; different types transcribed from different genes
progesterone receptors
both isoforms derived from same gene but have different modes of action
adrenal medulla
contains chromafin tissue; part of the sympathetic nervous system
adrenal cortex
secretes steroid hormones
zona glomerulosa
outer layer of the adrenal cortex; controlled by renin-angiotensin. produces aldosterone
zona fasiculata
middle layer of the adrenal cortex; controlled by ACTH, produces cortisol
zona reticularis
inner layer of the adrenal cortex; controlled by ACTH, produces androgens
location of catecholamines (epinephrine)
adrenal medulla; tyrosine derived and influenced by cortisone
adrenal medullary product in response to stress
norepinephrine
relationship of alpha and beta adrenergic receptors
alpha dominates beta. beta generally stimulatory to cell secretion; alpha generally inhibitory
first step in steroid synthesis
cholesterol side chain cleaveage by Side Chain Cleavage enzyme (SCC)
Steriod Acutely Regulated protein (StAR)
cholesterol transporter functioning between inner and outer mitochondrial membranes
21 Hydroxylase
critical enzyme in aldosterone and cortisol production; deficiency is known as adrenal hyperplasia
control of the adrenal cortex
CRH stimulates ACTH-CRH; daily rhythm in plasma ACTH and cortisol
effects of hypovolemia
decreased plasma osmolarity, renin secretion, converts angiotensinogen to angiotensin I, converted to angiotensin II, stimulates zona glomerulosa to produce vasopressin
glucocorticoid influences on peripheral tissues
antiinflammatory, stabilizes lysosomal membranes, maintains normal blood pressure and kidney function, decreases histamine release, generally permissive
glucocorticoid influence on prostaglandins
inhibitory; prevents release of precursor molecule from lipids and decreases release of precursor molecules from lipids
atrial naturietic factor
stimulated by atrial distension, leads to natriuresis (salt excretion) and decreased renin production, angiotensin II, aldosterone and vascular resistance
Effects of ANP system
increases GFR; decreasing blood pressure and volume
function of thyroid gland
establishes a baseline metabolic rate; produces T4 and T3
parathyroid
glands involved in Calcium ion regulation
thyroid follicular cells
secrete T3 and T4
thyroglobulin
stored in thyroid lumen; iodine in incorporated in tyrosine residues to become thyroxine
thyroxine
fully iodized thyroglobulin; contains 4 iodines
T3 triiodo thyronine
biologically significant; acts with a shorter pathway than T4