Endocrine System & Growth

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Nickola Lecture

What is the maintenance of relatively constant internal environment?

homeostasis

What is local regulation of physiologic responses via locally-derived mediators?

Intrinsic regulation aka autoregulation (at the site where something is going wrong)

what is it called when the nervous and endocrine systems regulate physiologic responses (non-local; systemic)?

extrinsic regulation

What is the neuronal circuit that directs a specific motor response - the reaction usually opposes initial stimuli (negative feedback)?

reflex arc

what are feedback loops that regulate homeostasis?

endocrine reflex arcs

components of endocrine reflex arc

receptors (sensitive to particular stimuli)
Integration center (usually CNS. receives and processes info from receptor and sends out commands)
Effector (cell/organ responding to commands; Can oppose or enhance initial stimuli)

**MOST ENDOCRINE REFLEXES ARE NEGATIVE (NOT POSITIVE) FEEDBACK LOOPS**

**MOST ENDOCRINE REFLEXES ARE NEGATIVE (NOT POSITIVE) FEEDBACK LOOPS**

What triggers endocrine reflexes? aka what are the stimuli?

humoral stimuli
hormonal stimuli
neural stimuli

type of stimuli that is a change in composition of extracellular fluid? eg. change in blood osmolarity (triggers an endocrine reflex)

humoral stimuli

type of stimuli that is presence or absence of hormone at its receptors?

hormonal stimuli

type of stimuli that is the NT present at the neuroglandular junction

neural stimuli

______ is how the nervous system regulates the endocrine system.

neuroendocrine

types of intercellular signaling

endocrine signaling
neurocrine
neuroendocrine

____signaling involves cells that secrete chemical messengers into bloodstream.

endocrine (hormones)

____ signaling involves neurons releasing chemical messengers that enter the bloodstream

Neurocrine (neurohormone)

____signaling is when a neuronal action potential results in the release of hormones from endocrine cells.

neuroendocrine

At any given point in time there are a multitude of hormones circulating in the body. What are the effects of multiple hormones on one target tissue?

Antagonistic
Synergistic
permissive
integrative

In what type of response are the effects weaker than those produced by either hormone acting alone/unopposed. The net result depends on the balance between the 2 hormones?

antagonistic (ex. insulin lowers blood sugar, glucagon increases it)

In what type of response are the effects greater than those produced by either hormone acting alone? The 2 hormones are additive

synergistic (ex. milk production and secretion requires estrogen, progesterone, and prolactin)

If hormone A is needed for hormone B to produce its effect - what type of response is this?

permissive (ex. thyroid increases number of receptors available for epinephrine at the latter's target cell)

If hormone A and B produce different results, the the result complement each other - what type of response is this?

integrative (ex. LH & FSH in ovum maturation.

hormones of the body can be divided into 3 groups based on their chemical structure

amino acid derivatives
peptide hormones
lipid derivatives

amino acid derivatives

derivatives of tyrosine - thyroid hormones, catecholamines (epi, NE, Dopamine)
Derivatives of tryptophan - melatonin

peptide hormones

chains of amino acids strung together
Can be glycoproteins: >200 aa + carbs
Can be short polypeptides and small proteins: <200 aa

lipid derivatives

Eicosanoids (derived from arachidonic acid)
steroid hormones (derived from cholesterol)

How do hormones exert their effects?

hydrophilic cell membrane receptor (GPCR, ion channel-linked, enzyme-linked)
Lipophilic intracellular receptors (eg. steroids)

Which hormones exert their effect by hydrophilic cell membrane receptor?

peptides and some amino acids

Which hormones exert their effects by lipophilic intracellular receptors?

steroid

Growth is controlled by several endocrine hormones:

Growth hormone
Thyroid hormone
Insulin
Parathyroid hormone
Calcitriol
Reproductive hormones

What are the major endocrine glands involved in growth?

hypothalamus
pituitary gland
pineal gland
gonads (and placenta! during gestation)

anterior pituitary also known as _______ consists of ____tissue and produces _ hormones.

adenohypophysis; glandular; 7

posterior pituitary also known as _______ consists of ___ tissue and produces _ hormones

neurohypophysis; neural; 2

hypothalamic-pituitary hormones are ______ hormones

Peptide

How are H-P hormones released?

usually released in pulsatile fashion (not constant, comes in bursts) therefore the frequency of pulses and amount of hormone released influences the response of target tissue

What organ is considered the highest level of endocrine control?

Hypothalamus

Neurons in the hypothalamus integrate the nervous and endocrine systems in 3 ways:

1. exerts direct neural control over endocrine cells via hypothalamic nuclei that directly innervate adrenal medulla and regulate hormone secretion
2. hypothalamus secretes regulatory hormones that regulate secretory activity of endocrine cells in the anterior pituitary.
3. the hypothalamus itself acts as an endocrine organ - hypothalamic nuclei synthesizes hormones and releases them into circulation

______ in hypothalamus directly regulate ____ cells of the _____ _______ to release EPI & NE. hormones are released in response to action potentials (not other hormones) = _______.

neurons; endocrine; adrenal medulla; neuroendocrine

describe the hypophyseal portal system.

connects 2 capillary beds:
Artery(+O2) -> hypothalamic capillary bed -> portal vein -> anterior pituitary capillary bed -> vein(-O2)

What feature enables the diffusion of larger molecules into/out of the vasculature?

fenestrated capillaries (not connected to neighboring cells by tight junction)

Neurons in the hypothalamus (primarily in the ______ ______) synthesize, pack and transport ______ ______ which are released into ECF -> capillary bed -> _____ ______ _____ -> capillary bed of _____ ______

median eminence; regulatory hormones; hypophyseal portal circulation; anterior pituitary

The hypothalamic ____ _____ cause the endocrine cells of the ____ pituitary to release a hormone into systemic circulation; this is another example of ______ effect.

regulatory hormone; anterior; neuroendocrine

secretion of _____ _____ from the hypothalamus control activity of the anterior lobe of the pituitary.

regulatory hormones

What stimulates the synthesis and secretion/release of hormone from anterior pituitary? (ie. GH-RH)

releasing hormone

What prevents synthesis and secretion of hormone from anterior pituitary? (ie. GH-IH)

Inhibiting hormone

This hormone is released from the anterior pituitary and stimulates cell growth/division by increasing protein synthesis. Especially skeletal and cartilage.

Growth hormone/somatotropin

How is Growth Hormone release regulated?

1. GH-RH aka somatocrinin
2. GH-IH aka somatostatin
both are released from hypothalamic nuclei and results in release or inhibition, respectively, of GH from somatotrophs in the anterior pituitary

cell in the anterior pituitary that have receptors for GHIH and GHRH are called what?

somatotrophs

what are the Direct effects of GH on muscles? (GH doing the work)

increase a.a. uptake and protein synthesis
increase myoblast differentiation & proliferation

How is glucose involved in the effects of GH?

direct effects of GH occur when glucose levels are normal or low.

What are the direct effects of GH on adipose?

increase lipolysis. GH stimulates break down of stored FA by adipocytes, which release FA into blood. as circulating FA levels rise, many tissues stop breaking down glucose to generate ATP and instead start breaking down fatty acids. (glucose-sparing effect)

What are the direct effect of GH on the liver?

increase of glycogenolysis (breakdown of glycogen stores) by liver cells
Increase Insulin-like Growth Factor (IGF) aka somatomedin productions/secretion

indirect effects of GH (IGF doing the work) important wen glucose levels are high (eg. after a meal)

Muscles: increase uptake of glucose and a.a.; increase glycogenesis; increase protein synthesis
Chondrocyte stimulation: linear bone growth

What is IGF?

Insulin-like Growth Factor aka somatomedin
-produced by liver in response to GH. "hormone 2"

Explain the sequence of negative feedback in the regulation of GH secretion

1. GH-RH inhibits its own release from the hypothalamus
2. IGF (aka somatomedin) inhibits release of GH from anterior pituitary
3. GH & IGF stimulates production of GH-IH (aka somatostatin) from hypothalamus
-decreased release of GH from anterior pituitary

Disorder caused by pituitary hyposecretion; hyposecretion of GH during childhood. Treatments include hormone replacement.

Dwarfism

Disorder caused by hypersecretion of GH in childhood. Treatments include surgery of pituitary tumor, and RX drugs: GHr antagonist and/or somatostatin analog (not very successful; removal of tumor is best)

gigantism

disorder caused by hypersecretion of GH in ADULTS. Cartilage and small bones respond causing enlargement of jaw/skull, extremities. Treatments include surgery if pituitary tumor. Rx drugs: GHr antagonist and/or somatostatin analog (more effective here than gigantism)

Acromegaly (more common than gigantism)

Explain the problems with rbGH (recombinant bovine growth hormone)

cows end up with infection - treated with antibiotics and steroids - antibiotic resistance = sad cow
IGF-1 is secreted into milk; similar affinity for hGH-R

Effects of IGF on cell proliferation

IGF turns on cyclins cells
Cancer cells with increased expression of IGF

Thyroid releasing hormone (TRH) is released from _________ ____ which stimulates anterior pituitary ________ to release _______.

hypothalamic nuclei; thyrotrophs; TSH

Target tissues of TSH

follicle cells of thyroid gland
TSH regulates all aspects of thyroid hormone synthesis and release (T3 & T4 'hormone 2')

Explain negative feedback in the role of TSH from the anterior pituitary

T3 & T4 inhibit further release of TSH from thyrotrophs & inhibit TRH release from hypothalamus

Adrenocorticotropic hormone (ACTH) aka corticotropic

CRH from hypothalamus -> stimulates ant. pit. -> corticotrophs release ACTH

target cells of ACTH

zona fasciculata of adrenal cortex
-release corticosteroid (hormone 2) ie. cortisol, glucocorticoids

Explain negative feedback in the role of ACTH from the anterior pituitary

corticosteroids inhibit further release of ACTH from anterior pituitary/corticotrophs and CRH release from hypothalamus

Prolactin releasing factors (PRF) and prolactin inhibiting hormone (PIH) aka ______ is released from where?

dopamine; hypothalamic nuclei

in the anterior pituitary, _______ release prolactin

mammotrophs

What are the targets of prolactin?

-mammary gland development and milk production
-regulates androgen production from testes

Explain negative feedback in the role of prolactin from the anterior pituitary

prolactin inhibits its own release from mammotrophs and release of PRF from the hypothalamus.
prolactin also increases release of PIH from hypothalamus.
(prolactin inhibits prolactin, prolactin inhibits PRF, prolactin increases PIH)

LH and FSH are released from ______ in the anterior pituitary

gonadotrophs

the release of LH and FSH from the anterior pituitary is controlled by _______ from the hypothalamic nuclei

gonadotropin releasing hormone (GnRH)

What are the targets of LH & FSH?

Gonads (produce hormone 2):
Testes release androgen
ovaries promotes follicle development & release estrogens, progestins

Explain negative feedback in the role of FSH & LH from the anterior pituitary

sex hormones (estrogens, progestins, androgens) inhibit further release of FSH & LH from gonadotrophs and GnRH release from hypothalamic nuclei

What does GnRH do? where is it released from?

GnRH released from hypothalamic nuclei; stimulates release of LH & FHS from anterior pituitary.

What does LH do? where is it released from?

released from gonadotrophs of anterior pituitary.
targets Gonads - ovaries and testes.
stimulates release of progestins and estrogens from ovaries
stimulates release of androgens from testes

What does FSH do? where is it released from?

released from gonadotrophs of anterior pituitary.
targets gonads - ovaries and testes.
stimulates release of estrogens from ovaries
stimulates release of testosterone from testes.

puberty normally occurs at what age in girls? boys?

girls: ~10yrs.
boys: ~12yrs.

precocious puberty is when puberty occurs earlier than normal. What age is this in girls? boys?

< age 7 in girls
< age 9 in boys

What are the symptoms of precocious puberty in girls? boys? both?

girls: breast development, menstruation
boys: enlargement of genitalia, deeper voice
both: acne, body hair, growth spurt

What are the major concerns that result from precocious puberty?

self esteem issues
teasing by peers
loss of childhood
emotional trauma
aggressiveness
age-inappropriate sex drive
breast cancer (due to unopposed release of sex hormones)
Correlation with onset of menopause
growth spurt -> short stature

Explain the etiology of precocious puberty

usually not ovarian or testicular dysfunction
Hypothalamus triggers pituitary to release FSH, LH etc. -> puberty
other possible causes: brain tumor, CNS infection, head trauma?
*GH & IGF play a role in puberty; therefore, a lot of finger pointing in the dairy industry and where rbGH is causing endocrine disruption

What does melanocyte stimulating hormones released from the anterior pituitary stimulate?

stimulates melanin production from melanocytes in the skin
MSH production in adult humans usually occurs LOCALLY (skin) - normally NOT produced by the anterior pituitary.

When does production of MSH from anterior pituitary occur?

fetal development
pregnancy
very young children
disease states

Neurons in the________extend into the posterior pituitary and release hormones into _____.

hypothalamus; ECF

____enters capillaries -> systemic circulation

hormone

2 groups of hypothalamic nuclei

supraoptic nuclei
paraventricular nuclei

antidiuretic hormone (ADH) aka ______ is released from _____ ______, synthesized in _____ _______ ______. It regulates _____ and _____ balance by decreasing urination.

vasopressin; posterior pituitary; hypothalamic supraoptic nuclei; water; electrolyte

What stimulates ADH secretion?

1. increased plasma osmolarity - detected by osmoreceptors (supraoptic nuclei) in hypothalamus
2. decreased plasma volume - detected by baroreceptors in periphery (aorta, carotid artery)

What is the target of ADH secretion?

Increased ADH results in H2O retention by kidney.

Oxytocin (OXT) is released from ______ ______, synthesized in ______ ______ _____. It functions in ______ _______ and _____ ______

posterior pituitary; hypothalamic paraventricular nuclei; uterine contractions; milk ejection

What is the role of OXT in uterine contractions?

stimulates smooth muscle of uterus
-may also be trigger for labor
-also released by placenta and fetus

the 2 groups of nuclei in the hypothalamus are considered _________ effect

neurocrine

What is pitocin?

exogenous oxytocin
oxytocin analog
labor induction and placental delivery

what is the role of OXT in milk ejection?

sensory endings in breasts are stimulated by sucking
oxytocin is released into circulation from posterior pituitary
oxytocin release causes contraction of myoepithelial cells in breast alveoli
milk ejected from breasts
milk ejection stimulates prolactin secretion which increases milk production

prolactin + OXT is a _______ effect. Explain this concept

synergistic - prolactin from acterior pituitary produced milk and oxytocin from posterior pituitary causes milk ejection

______ synthesize melatonin from tryptophan in the _______ gland.

pinealocytes (cells of pineal gland); pineal

collaterals from the visual pathway (______ ______) enter pineal gland and influence _______ production, which is highest at nighttime.

suprachiasmatic nucleus (of hypothalamus); melatonin

Functions of melatonin

1. inhibits reproductive functions
2. free radical scavenger - acts as antioxidant
3. establishes circadian rhythms

explain how melatonin inhibits reproductive functions

decreses sperm and oocyte maturation (via decreased GnRH)
-melatonin receptors in hypothalamus & pituitary
-melatonin levels decline at puberty

How does melatonin establish circadian rhythms?

because melatonin activity is cyclic, it can help maintain sleep/wake cycles
-low sunlight in winter results in higher melatonin levels and may contribute to seasonal depression
-melatonin supplements may help with insomnia (& jet lag)

melatonin receptors in hypothalamus and pituitary cause decrease in _____

GnRH

What hormones and glands are involved in male fertility?

1. GnRH from hypothalamus - consistent, constant fashion, except pulsatile release @ puberty (unlike females)
2. FSH - stimulates spermatogenesis in sertoli cells (testosterone needed too) - Feedback: sertoli cells (nurse cells) produce inhibin (hormone 2) to decrease FSH (& perhaps GnRH) secretion
3. LH - increases testosterone production in Leydig cells (interstitial cells) - Feedback: testosterone inhibits GnRH release

How is testosterone involved in male reproductive function?

secondary sex characteristics
bone & muscle growth
libido
spermatogenesis

What is the role of sertoli cells (nurse cells) in male reproductive function?

stimulated by FSH & Testosterone
secrete inhibin (decreases FSH and perhaps GnRH)
produce androgens - testosterone which stimulates spermatogenesis

what is the role of leydig cells (intersitial cells) in male reproductive function?

produce androgens - most importantly, testosterone

What hormone stimulates Leydig cells which secrete testosterone

LH from gonadotrophs in anterior pituitary

What hormone(s) stimulates sertoli (nurse cells) cells which stimulate spermatogenesis and release of inhibin?

FSH from gonadotrophs in anterior pituitary
testesterone from leydig cells

What hormones and glands are involved in female reproductive function?

1. GnRH from hypothalamus - stimulates FSH & LH from anterior pituitary
2. FSH from ant. pit. - follicle stimulation and egg maturation - stimulates estrogen which causes proliferation of endometrium, thins cervical mucus, inhibits GnRH & FSH production
3. LH from ant. pit. - ovulation stimulation - stimulates Progesterone (and Estrogen) which causes differentiation/maintenance of endometrium, thicken cervial mucus, inhibits GnRH & LH production
4. Inhibin: from mature ovum decreases FSH

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