Endocrine Physiology Flashcards by Scott Mitchell

Renin review

Secreted by the kidneys (specifically granular cells in the afferent tubules) in response to low blood pressure/perfusion

Gets secreted into blood system via endocrine functions which then goes to liver to secrete angiotensinogen which gets cleaved into angiotensin and then moves to lungs which makes angiotensin-2

Angiotensin 2 works as a small vasoconstrictor but also activates aldosterone which both vasoconstriction and increases water retention

End goal = increase blood pressure

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Cholecalciferol review

Absorbed as inactive vitamin D3 by skin

Liver converts it into 25-hydroxycholecalciferol

Kidney (with activation by PTH) converts it into 1,25 Dihydroxycholecalciferol which then acts in the intestinal epithelium by trying to bind as much calcium as possible and increase plasma ion concentration fo calcium

Does this through three mechanisms

1) upregulates calcium binding protein production
2) stimulates calcium stimulated ATPase enzymes activity
3) upregulates alkaline phosphatase enzymes

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Erythropoietin review

Hormone secreted by kidneys to stimulate proerythroblast differnetiation and stimulates growth of RBCs

Stimulated in response to decreased oxygen saturation to tissues

Factors:

poor blood flow
pulmonary disease
anemia
low blood volume or hemoglobin

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Pineal gland

Produces melatonin with stimulation based on the supraoptic chiasm nucleus exposure to light

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What hormone does the heart secrete?

ANP

- in response to high blood pressure and essentially antagonizes aldosterones effects

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General steps in peptide hormone synthesis

1) DNA is transcribed in the nucleus into mRNA
2) mRNA is then converted by ribosomes into preprohormone
3) preprohormone is then converted by the ER into prohormone
4) prohormone is then converted into hormones by both conversion and secretion from the Golgi apparatus

this is done via increased intracellular cAMP and calcium inside hormone cells

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What is the only cell type in which low intracellular calcium actually stimulates the cells action?

Parathyroid cells

- secrete PTH in response to low intracellular calcium

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Pseudohypoparathyroidism

Is caused by broken Gs protein receptors

- there is low calcium in blood but high PTH in blood

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Receptors and downstream effects

1) AC and cAMP pathway via Gs receptor
- activates
- require stimulation of the a-subunit of the Gs receptor
- vast majority of hormones this pathway*

2) PLC and IP3/DAG pathway via Gq receptors
- activates PLC via a-subunit activation and increases intracellular calcium and PKC levels
- common = AVP/ADH, Ang-2, GHRH and GnRH, PTH, oxytocin, ACh and catecholamines

3) extraceullar receptors for GC and cGMP
- stimulates Guanine Cyclase enzymes which upregulates cGMP
- common in NO, ANP and ACh effects

4) insulin-like tyrosine kinase receptors and domains
- casues protein phosphorylation and JAK/STAT pathway and produces STAT3 proteins to which bind to promotor regions on DNA
- used by insulin and GH, leptin, VEGF, IGF-1**

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Steroid hormones

All are made from the precursor cholesterol
- includes: cortisol/aldosterone/estradiol/progesterone and testosterone

They are made on demand and NOT stored

Adrenal cortex or gonads are the only places top make these hormones

ALL have the intermediate of pregnenolone

All bind to INTRACELLULAR steroid receptors to induce actions. Are found in cytosol or nucleus
- all upregulate proteins/receptor actions

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Amine hormones

**Includes Catecholamines, serotonin and both T3/T4 hormones

**Are all made from tyrosine as its precursor except serotonin which is tryptophan

Are mostly stored but some are made on demand

Catecholamines bind to EXTRACELLULAR receptors, but thyroid hormones bind to INTRACELLULAR receptors

catecholamines receptors:
B1/2 = Epinephrine = upregulates AC and cAMP
A1/2 = Norepinephrine
- a2 = inhibits AC and cAMP; a1 = upregulates DAG + IP3.
D1/2 = dopamine
- D1 = upregulates AC and cAMP; D2 = inhibits AC and cAMP

Gi = a2/D2

Gs = B1/B2 and D1

Gq = a1

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Types of globulin found in body related to hormones

These are hormone binding proteins that help move it and/or prevent early degradation

**NOTE: free hormone always has greater biological activity

1) corticosteroid binding globulin (CBG)
- binds cortisol and aldosterone
- decreases in cirrhosis, nephrotic syndromes, hyperthyroidism and malnutrition

2) sex hormone-binding globulin (SHBG)
- binds estrogen and testosterone
- increases by levels of estrogen and exogenous thyroid hormones

3) thyroxine-binding globulin (TBG)
- binds T3/T4
- increases by levels of estrogen and if the patient is pregnant

4) serum albumin
- rarely binds T3/T4
- decreases in cirrhosis, nephrotic syndrome and malnutrition

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How does hypothalamic pituitary axis differ between posterior and anterior pituitary

Posterior:

hypothalamus Neurons directly synapse on the posterior lobe of the pituitary to induce it to secrete ADH/oxytocin hormones out into blood stream
works via direct stimulation from neurons

hypothalamus secretes hypothalamic trophic hormones within the hypothalamus which goes into hypothalamic-hypophyseal portal vessels to make its way to the anterior pituitary secrete its hormones
works via endocrine

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What are the three subsections of the adenohypophysis?

Pars tubularis (portion that is part of infundibulum)

Pars intermedia (portion that is closest to the posterior lobe and separates anterior from posterior)

Pars distalis (primary portion of the adenohypophysis)

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Paraventricular nucleus vs supraoptic nucleus

Paraventricular nucleus
- releases oxytocin in response to uterus contractions/stretching and suckling at lactating breast

Supraoptic nucleus
- releases ADH in response to osmoreceptors detecting high serum osmolarity

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AVP

Hormone that increases aquaporins in CD which promotes reabsorption of water into the serum

Is released by the supraoptic nuclei cells in response to increase hypoosmolarity serum or > 10% drop in plasma

Binds to V2 receptor found in CD’s of nephrons
- is a Gs protein receptor which upregulates AC and cAMP and moves intracellular vesicles with aquaporins to the cell surface

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Factors that increase and decrease ADH secretion

Increases:

Plasma osmolarity increased
Large plasma volume drop
Large drop in blood pressure
consumption of nicotine and opiates

Decreases:

plasma osmolarity decreased
large plasma volume increase
large increase in BP
consumption of ethanol

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Differences between Central DI Nephrogenic DI and primary polydipsia

Central DI

caused by posterior pituitary or hypothalamus issue of hyposecretion of ADH
NO INCREASE in urine concentration with water deprivation (can’t reabsorb water)
DOES respond to injection of ADH (urine becomes concentrated)

Nephrogenic DI

caused by inability of renal cells to respond to ADH due to broken V2 receptors on CD
NO INCREASE in urine concentration with water deprivation (cant reabsorb water)
DOESNT respond to injection of ADH (there is still very diluted urine

Primary polydipsia (excessive drinking)

URINE OSMOLALITY INCREASES with water deprivation
DOES respond to injection of ADH

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Oxytocin

Functions:

contracts myoepithelial cells of the breast near the nipples to induce lactation
both induces initial uterine contractions during birth and also induces positive reinforcement on said contractions

Suckling of breast and stretching of cervix induces positive feedback on the paraventricular nucleus

Is secreted via the paraventricular nucleus

What are the main hormones released from the anterior pituitary and the hypothalamic hormones/neurotransmitters that regulate these hormones

1) Thyroid stimulating hormone
- is positive controlled by Thyroid releasing hormone (TRH) from the hypothalamus
- released via thyrotrophs
- function is to stimulate thyroid into release T3/T4

2) Prolactin
- is Negatively controlled by dopamine (prolactin inhibiting factor) in the
hypothalamus
- released via lactotrophs
- when dopamine isnt blocking it, prolactin is tonically active and always secreting from anterior pituitary
- function is to produce breast milk

3) Growth hormone
- is positive controlled by GHRH and negatively controlled by somatostatin (growth inhibting hormone)
- released from somatotrophs
- both of the above from the hypothalamus
- function is to do anabolic actions and upregulate insulin-like growth factor 1 to induce bone growth. Also other functions as well

4) ACTH
- is positively controlled by corticotropic releasing hormone
- released by corticotrophs
- function is to bind to the adrenal cortex and induce cortisol secretion

5) FSH/LH
- both are positively controlled by GnRH from the hypothalamus
- released by gonadotrophs
- function is numerous

What are the anterior pituitary hormones classified as glycoproteins

TSH

FSH

All have the same a-subunit but unique B-subunits

What anterior pituitary hormone is commonly referred to as Pro-oplomelanocortin? (POMC)

ACTH

Prolactin regulation

Essential for milk production and is induced via suckling on the breast
- upregulates synthesis of lactose, casein and lipids which are all needed for milk production

Is negatively inhibited by dopamine
- prolactin is tonically activate, but if dopamine is present, overrides this

strangely can actually be induced by TRH also, but dopamine is the strongest controller of prolactin and under normal conditions dopamine inhibits this

Can also be induced behaviorally via sight/cry of newborns directly related to mother
- this turns off hypothalamus and increases prolactin since dopamine isnt inhibiting as much since there is less

Exhibits positive reinforcement of secretion via suckling and release of prolactin

Also is positively induced via pregnancy and estrogen secretion

*Prolactin and pregnancy turns off GnRH which inhibits FSH and LH and leads to decreased fertility and ovulation (patient is already pregnant so dont need to be more pregnant)
this is also why if males have hyperprolactinemia they exhibit infertility

What is the only pituitary hormone that actually increases in level if the pituitary stalk is severed/lesioned

Prolactin

- this is because the pituitary stalk houses the dopamine neurons which are severed and increase prolactin elvels

What are the 4 primary effects of suckling have on a Female?

1) increases Afferent activity to the CNS 2) inhibition of dopamine release 3) increase release of prolactin and increase oxytocin release by increasing activity of the paraventricular nucleus 4) decreasing levels of GnRH and consequently decreases in FSH/LH and turn off of the menstration cycle

GHRH is released from where in the hypothalamus

Arcuate nucleus

Somatostatin is released from where in they hypothalamus

Periventricular region **Dont get confused for paraventricular region which releases oxytocin**

How does GHRH and somatostatin specifically act on somatotrophs

GHRH 1) binds to GHRH receptor which is Gs proteins and upregulates AC/cAMP -> upregulates PKA which brings calcium into the somatotrophs 2) increased calcium allows for secretion of growth hormone Somatostatin 1) binds to SS receptor which is a G1 protein and downreagultes AC/cAMP and turns of PKA which decreases increases intracellular calcium and inhibits GH vesicle release

What are somatomedins?

Are insulin growth-like factors (IGF-1) released by the liver and other tissues when GH is bound to it Inhibit the anterior pituitary directly similar to somatostatin as well as increases somatostatin release from hypothalamus by binding to the periventricular region Also inhibits arcuate nucleus in the hypothalamus which prevents GHRH release

What are extra hormonal effects that turn off or on GHRH secretion

Increases - sleep (specifically deep sleep stages 2/4) - hypoglycemia - stress - low FAs in blood - increased levels of arginine AA in blood - starvation or fasting - testosterone and estrogen in high levels - high levels of ghrelin Decreases - aging - obesity - hyperglycemia - increased FAs in blood - high levels of IGF-1/somatostatin/ GH levels

All effects of growth hormone and IGF on body tissues (NOT CNS)

Increases: - amino uptake - protein synthesis - DNA/RNA synthesis - Chondrotin sulfate production - collagen production - cell size and numbers - amino acid uptake - protein synthesis - lipolysis Decreases: - glucose uptake

What are the anti-insulin effects of GH?

Hyperglycemia Increased lipolysis Increased gluconeogenesis Increases insulin resistance **Also referred to diabetogenic-like** This occurs due to IGF-1 binding to receptors similar to insulin receptors and sometimes actual insulin receptors. However when bound to insulin receptors it prevents glucose from being reabsorbed. also establishes insulin resistance (since the receptors are being chronically activated)

How is GH secreted from somatotrophs?

In “pulsitile” waves that is strongest at nights

Why is IGF called IGF?

Because the receptors they bind to are similar to the insulin receptor (tyrosine kinase domains) They also sometimes bind to actual insulin receptors, but don’t induce actions. Instead they block them and promote insulin resistance to the receptors

What are the exact effects of GH?

By itself, it does nothing, however it does upregulates production of insulin-like growth factor (IGF-1) or somatomedin - IGF-1 is produced by liver/kidney/muscle/cartilage and bone IGF-1 then acts on tragets via tyrosine kinase receptors that are structurally similar to insulin receptors

Why does excess GH cause polydipsia?

Excess glucose in the body (due to anti-insulin effects) causes increased filtered load of glucose in the tubular fluids of the kidneys Increases in glucose in the tubular fluids causes osmotic diuresis since sodium and water stays in tubular fluid (osmotic gradients)

Why can anterior pituitary lesions cause prolactinemia?

If the lesions get big enough, can cause lactotrophs to be removed from dopamine neurons Remember that dopamine is tonically produced to inhibit prolactin levels, so if dopamine is disabled then prolactin is tonically secreted

Why do anterior pituitary lesions sometimes cause amenorrhea or infertility?

Growth of anterior pituitary lesions (similar to prolactinemia) can cause gonadotrophs to be disabled This causes FSH and LH levels to decrease which causes improper sexual development and lowered secretion of estrogen Both of these cause menstration cycle to cease and can lead to infertility in men **also elevated prolactin levels due to disabled dopamine levels can cause amenorrhea as well**

What is usually the treatment for GH excess assuming it is a primary or secondary cause?

Octerotide | - this is a somatostatin analog which inhibits GH secretion

What is usually the 1st line treatment for prolactinemia caused by pituitary issues?

Bromocriptine (dopamine agonists)

What hormones and peptides inhibit ghrelin effects and hunger sensation?

Leptin hormones PYY and CCK release Stimulation of the vagus nerve

How does gastrin work as a hormone

Released from G cells and goes to parietal cells via endocrine and binds to CCK2 receptors on the parietal cells. - this secretes stomach acid Also goes to CCK receptors on D cells to promote somatostatin release. Somatostatin then goes to parietal cells to inhibit/control over production of stomach acid action via paracrine action - also binds to ECL cells to release histamine which stimulates parietal cells

How does vagus nerve affect GI cells

Promotes release of histamine from ECL cells by binding to M3 receptors Promotes parietal cell action by binding to M3 receptors Promotes gastrin release by binding to GRP receptors on G cells Inhibits somatostatin release by binding to M3 receptors on D cells

What are the most common paraneoplastic syndromes?

1) Cushing disease: caused by ectopic ACTH release from small cell of lung and pancreatic carcinomas 2) SIADH: caused by ectopic ADH release from Small cell of lung and intracranial neoplasms 3) hypercalcemia: caused by ectopic calcitonin release from SCC of lung, breast cancers and renal Cael carcinoma 4) MG via thymoma 5) hypertrophic osteoarthropathy via lung cancers 6) migratory venous thrombosis (trousseau syndrome) via pancreatic carcinomas 7) cancer cachexia via pretty much any cancer

Dwarfism vs laron-dwarfism

Normal dwarfism = GH Deficiency form the anterior pituitary - treatment = somatropin is #1 Laron-dwarfism = GH insensitivity in target tissues so no IGF1 it’s produced - treatment = Mecasermin is #1 Symptoms - hypoglycemia - short stature - insulin sensitivity increased