INTRODUCTION TO ENDOCRINOLOGY I ENDOCRINE SYSTEM M321 INTRODUCTION TO ENDOCRINOLOGY I

Homeostasis Homeostasis is the property of a system. Homeostatic system is one in which variables are regulated so that internal conditions remain stable and constant Human homeostasis is what maintains body's internal environment in response to changes in external conditions In humans, homeostasis is maintained by the concerted action of nervous and endocrine system

Endocrine glands: 1. Hypothalamus 2. Pituitary 3. Epiphysis 4. Thymus 5. Thyroid gland 6. Parathyroid glands 7. Langergans’ islands of pancreas 8. Adrenal glands 9. Gonads 3

Hormone Classification Hormones

Hormone Classification Hormones classified by source

Hormones What are they? Chemical messengers secreted by specialized cells From endocrine cells that make up the diffuse endocrine system From neurons From immune system cells producing cytokines Where do they go? Into blood (most) Into environment (ectohormones or pheromones)

Hormones Involved in Act by Growth Development Metabolism Reproduction Altering rates of enzyme mediated reactions Control the movement of molecules across the plasma membrane (Ion channels) Regulating the rate of gene expression (& therefore protein production)

Hormones How do hormones get from point A to B? To be classified as hormone & not a paracrine or autocrine hormone Travel in blood May require water soluble (protein) transport mechanism if hormone is lipid soluble Hormones act by binding to receptor on target cell surface or inside target cells Hormones need a mechanism to terminate their effect Stop/reduce production of hormone Degrade hormones Enzymatic removal from receptor Endocytosis of receptor-hormone complex

Hormone Hormones are mainly classified by their chemical structure

Hormone Hormones classified by structure Peptide/protein hormones Steroid hormones Amino acid based hormones Derived from tyrosine and may be Catecholamines Thyroid hormones

Hormone Classification Peptide/protein hormones Classification that includes most hormones If a hormone is not a steroid hormone or an amino acid derived hormone, then it is a protein/peptide hormone! Concerns with these hormones How are they made, stored and released How are they transported in blood Their mechanism of action How long does the signal last?

Hormone Classification Peptide/protein hormones & how they are made, stored and released

Communication Hormone Classification Examples of hormone processing PreproTSH (thyrotropin releasing hormone) has six copies of the 3-amino acid hormones TRH Prohormones may contain several peptide sequences that have biological activity The peptide chain of insulin’s prohormone folds back and is cleaved into insulin & C-peptide

Hormone Classification Peptide/protein hormones Cellular action mechanism Water soluble – must bind to receptors on target cell membrane Work via second messenger system

Hormones Steroid Hormones Lipophilic – creates problems No storage Production is on an “as needed” basis Can have the precursors in cytoplasm ready to go Require protein transporters in blood prolongs duration of hormone Blocks entrance into cell… it must disengage from carrier this follows law of mass action…

Hormones Steroid hormones Based on cholesterol Produced using SER in the Adrenal cortex Gonads Placenta Secretion is by simple diffusion

Hormones Steroid Hormones Cellular mechanism of action Diffuses into cytosol Bind with nuclear receptors ( a superfamily of transcription factors) Nuclear receptors are bound with heat shock proteins Binding of hormone releases heat shock proteins This allows nuclear receptor to translocate into the nucleus Nuclear receptors have DNA binding domains (DBDs) that allows them to bind on the DNA on hormone response element (HRE)

New(er) research indicates that steroid hormones have membrane receptors and signal transduction pathways similar in process to peptide/protein hormones This concept is known as Nongenomic action of hormones

Steroid hormones Steroid Hormone Action

Hormone Classification Amino acid derived hormones may be Derived from tyrosine Produces T3 & T4 Epinephrine & norepinephrine

Hormone Classification Amino acid derived hormones may be Derived from tyrptophan Produces Melatonin Serotonin* *serotonin is classified as a neurohormone as it is synthesized and secreted by neurons of the GI tract for regulation of motility and CNS

Regulation of hormone levels Hormones are controlled by negative feedback loops!

Feedback Loops Hypothalamus Anterior Pituitary Corticotropin releasing factor Adrenal Cortex + ACTH + Cortisol