Copyright, 1999 © Mark Chambers Endocrine Physiology Dr. Mark Chambers D.V.M., Ph.D.

Schedule:

Endocrinology: General Concepts n Definition of ‘hormone’ n Types of hormones n Synthesis and Release n Action: Receptors n Action: Second Messengers n Hormone Metabolism n Hormone measurement

What is a Hormone? n Endocrine n Neurocrine n Paracrine n Autocrine

Types of Hormones n Amines – catecholamines – thyroid hormone n Proteins – insulin – ACTH n Steroids – testosterone – progesterone

Hormone Synthesis n protein-peptide hormones – rough endoplasmic reticulum – golgi processing – preprohormone, prohormone, hormone

Hormone Synthesis n Amines – synthesized from amino acids n Steroids – synthesized from cholesterol

Hormone Release n Protein and catecholamine hormones: – Ca + mediated exocytosis – via G protein cAMP n Steroid and thyroid hormones: – via diffusion

Hormone Receptors n Binding to specific receptor on target cell – cell membrane associated receptors – intracellular receptors n Coupling to cellular signal generating mechanism n Intracellular changes – altered enzyme activity or concentration – stimulation of secretion – changes at the level of DNA

G protein Coupling n membrane proteins linking receptor to second messenger system  protein trimer n utilize GTP n may stimulate or inhibit the second messenger system n are “reusable” n contribute to amplification of receptor signal n ubiquitous and highly modified protein!

G Protein Function

Second Messenger Systems n Membrane bound systems – adenylyl cyclase - cAMP (G protein linked) – calcium-calmodulin system (G protein linked) – phospholipase C (G protein linked) – tyrosine kinase – guanylyl cyclase (G protein linked) n Intracellular systems – Steroid hormone receptor family

Adenylyl cyclase - cAMP n G protein linked membrane enzyme n protein kinase A activator – enzyme activation n cAMP regulatory element binding protein – gene activation/inactivation

Adenylyl cyclase

Calcium-calmodulin system n G protein linked membrane Ca + channel n increase in intracellular Ca + – Ca + - calmodulin enzyme activation – Ca + mediated secretory activity

Calcium-calmodulin

Phospholipase C n G protein linked membrane enzyme n generates diacylglycerol and inositol trisphosphate – diacylglycerol activates n protein kinase C - enzyme activation n prostaglandin synthesis – inositol trisphosphate - Ca + release from ER n enzyme activation

Phospholipase C

Tyrosine kinase n membrane bound receptor/enzyme n serine & threonine kinase activator – enzyme activation – gene activation/deactivation

Tyrosine kinase

Guanylyl cyclase n G protein linked membrane enzyme n protein kinase G activator – enzyme activation

Intracellular receptors n steroid hormone receptor family (cis-oncogenes) – steroid hormone receptors n cytoplasmic n bound complexes migrate to nucleus n bind with DNA n activate/deactivate genes – thyroid & vitamin D receptors n already bound to DNA n activate/deactivate genes n interact with DNA via “zinc finger” binding domain

Steroid family receptors

Whole Body Metabolism n Cool stuff