Hypothalamus/Pituitary Hormones

What is the hypothalamus?

highest level of endocrine control

integrates endocrine and nervous system

What are the sections of the pituitary?

aka hypophysis

anterior pituitary = adenohypohysis (derived from oral mucosa), includes pars distalis and pars intermedia, more protein/red on slide

posterior pituitary = neurohypophysis (derived from neural ectoderm), more fat/white on slide

What are the supraoptic and paraventricular nuclei?

nerves that feed into posterior pituitary

inenrvates hypohyseal artery to directly dump endocrine factors into plexus for delivery into circulation

How are hormones released from the anterior pituitary?

blood circulates down into pituitary but n nerves run all the way down

nerves secrete factors into blood and tell secretyr cells to release into lower plexus and circulated throughout the body

What hormones are released by the posterior pituitary?

ADH, oxytocin

all other hormones from anterior pituitary

What are the 2 main feedback loops?

short - hormone released from pituitary then directly feedsback onto hypothalamus

long - hormone from pituitary acts on another organ, that hormone then feedsback on the hypothalamus

What are peptide hromones?

chains of amino acids

have glycoproteins - large molecules w sugar chains released from pituitary (ie TSH, LH, FH)

or short polypeptides - ie ADH/oxytocin, ACTH, GH, or insulin

How do peptide hormones cause effects?

rapidly acting, bind membrane receptors linked to G-proteins

can then inhibit or stimulate cAMP which activates kinase that opens ion channels and activates enzymes (Gi or Gs respecitvely)

or activate PLC that produces IP3/DAG which activates PKC and leads to Ca2+ release (Gq)

What are lipid hormones?

carbon rings w side chains build from FA or cholesterol

eicosanoids - lipid derivatives of arachidonic acid (ie prostaglandins and thromboxanes)

steroid hormones - similar to cholesterol (androgens, mineralcorticoids, glucocorticoids)

How do lipid hormones cause effects?

diffuse through membrane lipids and bind cytoplasmic receptors

nuclear translocation and binding of hormone receptor complex to DNA

target cell responses either on itself or another cell

causes translation and protein synthesis for gene activation

non-steroid lipids tend to be fast acting (ie peptides)

What effects do steroid homrones have?

typically induce signaling pathways slowly as requires protein transcription/new protein synthesis

different cells synthesize/degrade different proteins at different rates (not all effects apparent at the same time)

What are amino acid hormones?

small molecules structurally related to individual amino acids

tryptophan derivatives (ie melatonin)

tyrosine derivatives (ie thyroxine - T3/T4, catecholamines)

How is urine concentration controlled in the CD?

ADH dependent aquaporins

ADH will bind Gs receptors

increases cAMP and activates PKA that causes AQ2 to bind to apical membrane and allow water to flow back into body and concentrate urine

AQ3 always present in basolateral membrane to pull water into blood

How does diabetes insipidus lead to increased hematocrit?

decrease in blood pressure (due to lack of water reabsorption) stimulates renin release

activates angiotensin and aldosterone/ADH secretion

also releases EPO to stimulate RBC production and increases hematocrit

What are the 3 main stimulus that triggers ADH secretion?

high osmolarity sensed by hypothalamic osmoreceptors

decreased atrial stretch from low blood volume

decreased blood pressure sensed by carotid/aortic baroreceptors

What is vasopressin used for?

ELDU

central diabetes insipidus Dx

vasoconstriction during caridopulmonary resuscitation/local bleeding (rare)

What is the pharmacodynamics of vasopressin?

endogenous replacement

equal affinity for V1 (in periphery to cause vasoconstriction), and V2 (kidney for AQ2 binding)

What makes vasopressin good for diagnostics of diabetes insipidus?

short half life and giving endogenous molecule

would expect pt to stop peeing/drinking and pressure to go up (if doesn’t then likely has nephrogenic DI as didnt respond to the hormone)

What are the pharmacokinetics of vasopressin?

SQ/IM

distributed through interstitial space

metabolized in liver/kidneys

short half life

What is Desmopressin used for?

ELDU

TX of central diabetes insipidus

What is the pharmacodynamics of desmopressin?

synthetic vasopressin replacement with modifications to make half life longer

has much higher affinity for V2 than V1 (no vasoconstrictive effects)

What are the pharmacokinetics of desmopressin?

Nasal spray admin - poorly tolerated but well absorbe din conjunctive, higher and lower dosages, absorption varies between individuals so dose to effect

Inj - used when conjunctival not tolerated

oral tablets - poor bioavailability due to hydrolysis of peptide

moderate rate of effect (2-6 hrs post conjunctival application, lasts 10-27 hrs)

What are the adverse effects of desmopressin?

increases factor 8 and von Willebrand factor in dogs

use w care in patients at risk of thrombotic events

What is somatotropin (GH) used for?

labeled for increased milk production in dair cattle

ELDU for pituitary dwarfism in dogs

not approved for increasing growth rate/meat quality in pigs, or lean-to-fat ratio in cows

What is the pharmacodynamics of somatotropin?

acts on liver secretes IGF1

increases fat utilization by ogans

increases glycogen hydrolysis

increases glucose available for milk

in mammary gland - increased blood flow, nutrient extraction

increased CO

What can cause milk output variability in cows on somatotropin?

works better in cows that have calved before

works better in lower temperatures (not shunting as much blood out to periphery and away from udder to keep cool)

consistency feed and feed-bunk management (need high quality feed)

What are the pharmacokinetics of somatotropin?

SQ in 14 day intervals

metabolism/excretion per endogenous protein

0 day withdrawal time (endogenous hormone and not secreted in milk)

What are the adverse effects of somatotropin?

implicated in mastitis/laminitis (not conclusive)

diabetes mellitus and acromegaly in dogs

reduce ketosis prevalnce (reduces milk production, life treatening)

increases 1st time pregnancy rate but decreases subsequent pregnancy rates (detection of estrous proportional to dose, insemination timing gamble)

increases twinning rate due to positive effects on follicle, endometrium, embryos