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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