Copyright, 1999 © Mark Chambers

Endocrine Physiology

Dr. Mark Chambers D.V.M., Ph.D.

Schedule:

April 19GeneralChapter 45

April 21PancreasChapter 47

April 23Ca-P metabChapter 48

April 26PituitaryChapter 49

April 28ThyroidChapter 50

April 30Adrenal 1Chapter 51

May 3Adrenal 2Repro 1Chapters 51-52

May 5Repro 2Chapter 52

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

What is a Hormone?

Endocrine Neurocrine Paracrine Autocrine

Types of Hormones

Amines– catecholamines– thyroid hormone

Proteins– insulin– ACTH

Steroids– testosterone– progesterone

Hormone Synthesis

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

Hormone Synthesis

Amines– synthesized from amino acids

Steroids– synthesized from cholesterol

Hormone Release

Protein and catecholamine hormones:– Ca+ mediated exocytosis– via G protein cAMP

Steroid and thyroid hormones:– via diffusion

Hormone Receptors

Binding to specific receptor on target cell– cell membrane associated receptors– intracellular receptors

Coupling to cellular signal generating mechanism Intracellular changes

– altered enzyme activity or concentration– stimulation of secretion– changes at the level of DNA

G protein Coupling

membrane proteins linking receptor to second messenger system

protein trimer utilize GTP may stimulate or inhibit the second messenger

system are “reusable” contribute to amplification of receptor signal ubiquitous and highly modified protein!

G Protein Function

Second Messenger Systems

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)

Intracellular systems– Steroid hormone receptor family

Adenylyl cyclase - cAMP

G protein linked membrane enzyme protein kinase A activator

– enzyme activation cAMP regulatory element binding protein

– gene activation/inactivation

Adenylyl cyclase

Calcium-calmodulin system

G protein linked membrane Ca+ channel increase in intracellular Ca+

– Ca+ - calmodulin enzyme activation– Ca+ mediated secretory activity

Calcium-calmodulin

Phospholipase C

G protein linked membrane enzyme generates diacylglycerol and inositol

trisphosphate– diacylglycerol activates

protein kinase C - enzyme activation prostaglandin synthesis

– inositol trisphosphate - Ca+ release from ER enzyme activation

Phospholipase C

Tyrosine kinase

membrane bound receptor/enzyme serine & threonine kinase activator

– enzyme activation– gene activation/deactivation

Tyrosine kinase

Guanylyl cyclase

G protein linked membrane enzyme protein kinase G activator

– enzyme activation

Intracellular receptors

steroid hormone receptor family (cis-oncogenes)– steroid hormone receptors

cytoplasmic bound complexes migrate to nucleus bind with DNA activate/deactivate genes

– thyroid & vitamin D receptors already bound to DNA activate/deactivate genes

interact with DNA via “zinc finger” binding domain

Steroid family receptors

Whole Body Metabolism

Cool stuff