ENDOCRINE PHYSIOLOGY

BY
DR. MUDASSAR ALI ROOMI (MBBS, M. Phil.)

INTERCELLULAR COMMUNICATION
Endocrine
Cell
Target Cell

Hormone

Blood

Hormone
Target Cell

Neuroendocrine

Neuron

Blood Hormone Hormone

Paracrine

Cell

Interstitial Fluid

Target Cell

Hormone

Hormone

Autocrine

Cell

Hormone

Interstitial Fluid

 Endocrine hormones are released by glands or specialized cells into the circulating blood and influence the function of cells at another location in the body.

Chemical Structure of hormones

There are three general classes of hormones: 1. Proteins and polypeptides 2. Steroids 3. Derivatives of the amino acid tyrosine

Steroid hormones
secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone).

STEROID HORMONES
GLAND/TISSUE
Adrenal Cortex

HORMONES
Cortisol, Aldosterone, Androgens Testosterone Estrogens, Progesterone Estrogens, Progesterone Estrogens, Progesterone 1,25-Dihydroxycholecalciferol

Testes Ovaries Corpus Luteum Placenta Kidney

 Proteins and polypeptides: including hormones secreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others.

PEPTIDE & PROTEIN HORMONES

Gland/Tissue
Hypothalamus

Hormones
TRH, GnRH, CRH GHRH, Somatostatin, ACTH, TSH, FSH, LH, PRL, GH Oxytocin, ADH Calcitonin

Gland/Tissue
Placenta

Hormones
HCG, HCS or HPL

Anterior pituitary

Kidney

Renin

Posterior pituitary Thyroid

Heart G.I. tract

ANP Gastrin, CCK, Secretin, GIP, Somatostatin

Pancreas

Insulin,Glucagon, Somatostatin Somatomedin C (IGF-1) Adipocyte

Liver

Leptin

Parathyroid

PTH

Adrenal medulla

Norepinephrine, epinephrine

 Derivatives of the amino acid tyrosine: secreted by the thyroid (thyroxine and triiodothyronine) and the adrenal medulla (epinephrine and norepinephrine).

Synthesis of Amine Hormones

tyrosine hydroxylase dopa decarboxylase Dopaminergic Neurons

Tyrosine

L-Dopa

Dopamine

dopamine hydroxylase
Adrenergic Norepinephrine Neurons phenylethanolamineN-methyltransferase

Epinephrine
Adrenal Glands

Thyroid Hormones
Thyroid Gland

SYNTHESIS & SECRETION OF PEPTIDE HORMONES

Types of Receptors

Hormone receptors
The locations for the different types of hormone receptors are generally the following: 1. In or on the surface of the cell membrane. The membrane receptors are specific mostly for the protein, peptide, and catecholamine hormones. 2. In the cell cytoplasm. The primary receptors for the different steroid hormones are found mainly in the cytoplasm. 3. In the cell nucleus. The receptors for the thyroid hormones are found in the nucleus and are believed to be located in direct association with one or more of the chromosomes.

down-regulation of the receptors

can occur as a result of: (1)inactivation of some of the receptor molecules, (2) inactivation of some of the intracellular protein signaling molecules, (3) temporary sequestration of the receptor to the inside of the cell, away from the site of action of hormones that interact with cell membrane receptors, (4) destruction of the receptors by lysosomes after they are internalized, or (5) decreased production of the receptors. In each case, receptor down-regulation decreases the target tissues responsiveness to the hormone.

up-regulation of receptors
Some hormones cause up-regulation of receptors and intracellular signaling proteins by: 1. stimulating greater than normal formation of receptor 2. or intracellular signaling molecules by the proteinmanufacturing machinery of the target cell, 3. or greater availability of the receptor for interaction with the hormone. When up-regulation occurs, the target tissue becomes progressively more sensitive to the stimulating effects of the hormone.

Cell surface receptors

Most are embedded in plasma membrane

Detect signals from extracellular environment

Three major types are :

1. Ion channel linked receptors (ligand gated and voltage gated) 2. G protein linked receptors 3. Enzyme linked receptors

Ligand-gated ion channels:

protein pores that open or close in response to a chemical signal.

Binding changes proteins shape to allow or block ion flow, such as Na+ or Ca2+. Ion flow changes the concentration inside the cell. e.g Ach gated channels in the sk. Muscles.

G-Protein coupled receptors

Cyclic Adenosine Monophosphate (cAMP) Second Messenger Mechanism

Cell Membrane Phospholipid Second Messenger System

JAK-STAT PATHWAY

Steroid & Thyroid Hormones - Mechanism of Action

1. The steroid hormone diffuses across the cell membrane and enters the cytoplasm of the cell, where it binds with a specific receptor protein. 2. The combined receptor protein hormone then diffuses into or is transported into the nucleus. 3. The combination binds at specific points on the DNA strands in the chromosomes, which activates the transcription process of specific genes to form mRNA. 4. The mRNA diffuses into the cytoplasm, where it promotes the translation process at the ribosomes to form new proteins.

SUMMARY

SUMMARY