In the name of GOD Iran Kashan university of medical sciences Faculty of medicine department of Physiology and pharmacology Mahdi noureddini Assistant professor of physiology Dr. Noureddini

Endocrinology and Reproduction Kashan university of medical sciences Faculty of medicine department of Physiology and pharmacology Mahdi noureddini Assistant professor Dr. Mahdi Noureddini

Introduction to Endocrinology Pituitary Hormones and Their Control by the Hypothalamus Thyroid Metabolic Hormones Adrenocortical Hormones Insulin, Glucagon, and Diabetes Mellitus Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth Reproductive and Hormonal Functions of the Male Female Physiology Before Pregnancy and the Female Hormones Pregnancy and Lactation Fetal and Neonatal Physiology Dr. Mahdi Noureddini

Introduction to Endocrinology Coordination of Body Functions by Chemical Messengers 1. Neurotransmitters 2. Endocrine hormones 3. Neuroendocrine hormones 4. Paracrine 5. Autocrines 6. Cytokines are peptides secreted by cells into the extracellular fluid and can function as autocrines, paracrines, or endocrine hormones. Examples of cytokines include the interleukins and other lymphokines that are secreted by helper cells and act on other cells of the immune system . Cytokine hormones (e.g., leptin) produced by adipocytes are sometimes called adipokines. Dr. Mahdi Noureddini

MODES OF HORMONE DELIVERY I: AUTOCRINE: Hormone released feeds-back on the cell of origin, again without entering blood circulation. PARACRINE: Hormone released diffuses to its target cells through immediate extracellular space. Blood is not directly involved in the delivery. Dr. Mahdi Noureddini

MODES OF HORMONE DELIVERY II: ENDOCRINE: Most common (classical) mode, hormones delivered to target cells by blood. NEUROENDOCRINE: Hormone is produced and released by a neuron, delivered to target cells by blood. Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Chemical Structure and Synthesis of Hormones 1. Proteins and polypeptides: 2. Steroids : 3. There are no known polysaccharides or nucleic acid hormones. Dr. Mahdi Noureddini

CHEMISTRY OF HORMONES Peptide hormones: largest, most complex, and most common hormones. Anterior(prolactin,FSH, LH,TSH) and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others(TRH-3,GH-200) Steroid hormones: lipid soluble molecules synthesized from cholesterol. adrenocortical steroids (e.g. cortisol and aldosterone). the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone). Amines: small molecules derived from individual amino acids. Derivatives of the amino acid tyrosine: thyroid (thyroxine and triiodothyronine) and the adrenal medullae (catecholamines: epinephrine and norepinephrine). Eicosanoids: small molecules synthesized from fatty acid substrates (e.g. arachidonic acid) located within cell membranes Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Amine Hormone Structures and Functions Made of 1-2 amino acids Receptors Surface Intracellular Small size, OH group Benzine ring Examples Thyroxin (Tyrosine) Epinephrine (Tyrosine) MELATONIN(Tryptophan) Dr. Mahdi Noureddini

Amine Hormone Structures and Functions Dr. Mahdi Noureddini Figure 7-8: Tyrosine-derived amine hormones

Dr. Mahdi Noureddini

Protein and Polypeptide Hormones: Synthesis and Release Dr. Mahdi Noureddini Figure 7-3: Peptide hormone synthesis, packaging, and release

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Lipid Hormone Steroid Hormones Eicosanoids Dr. Mahdi Noureddini

Steroid Hormones: Structure and Action From cholesterol, lipophilic, enter target cell, Cytoplasmic or nuclear receptors (mostly) Activate DNA for protein synthesis Slower acting, longer half-life Examples: cortisol, estrogen & testosterone Dr. Mahdi Noureddini

Steroid Hormones: Structure and Action Figure 7-6: Steroid hormones are derived from cholesterol Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Eicosanoids small molecules synthesized from fatty acid substrates (e.g. arachidonic acid) located within cell membranes Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

A Structural Classification of Hormones Dr. Mahdi Noureddini Figure 18.2

Hormone Secretion, Transport, and Clearance from the Blood Onset of Hormone Secretion After a Stimulus, and Duration of Action of Different Hormones Concentrations of Hormones in the Circulating Blood, and Hormonal Secretion Rates Dr. Mahdi Noureddini

Blood levels of the hormone STEROIDS(10-9-10-6m/l) Epinephrine and norepinephrine(10-10m/l) peptide(10-12m/l) Dr. Mahdi Noureddini

Feedback Control of Hormone Secretion Negative Feedback Prevents Overactivity of Hormone Systems. Surges of Hormones Can Occur with Positive Feedback. Cyclical Variations Occur in Hormone Release. Dr. Mahdi Noureddini

CONTROL OF HORMONE RELEASE: ( feedback ) The synthesis and secretion of most hormones are usually regulated by negative feedback systems. As hormone levels rise, they stimulate target organ responses. These in turn, inhibit further hormone release. The stimuli that induce endocrine glands to synthesize and release hormones belong to one of the following major types: Humoral Neural Hormonal Dr. Mahdi Noureddini

ENDOCRINE SYSTEM Dr. Mahdi Noureddini

Blood levels of the hormone Hormones ARE CONSTANTLY BE -SYNTHESIZED - BROKEN DOWN The actual concentration of a circulating hormone in blood at any time reflects: Its rate of release. The speed of its inactivation and removal from the body. Dr. Mahdi Noureddini

Clearance of Hormones from the Blood Feedback regulation of hormones can occur at all Two factors can increase or decrease the concentration of a hormone in the blood. the rate of hormone secretion into the blood The second is the rate of removal of the hormone from the blood, Metabolic clearance rate = Rate of disappearance of hormone from the plasma/Concentration of hormone in each milliliter of plasma Dr. Mahdi Noureddini

Clearance of Hormones from the Blood (1) metabolic destruction by the tissues, (2) binding with the tissues, (3) excretion by the liver into the bile, (4) excretion by the kidneys into the urine. Dr. Mahdi Noureddini

Transport of Hormones in the Blood Water-soluble hormones Steroid and thyroid hormones, Dr. Mahdi Noureddini

Mechanisms of Action of Hormones Hormone Receptors and Their Activation Intracellular Signaling After Hormone Receptor Activation Second Messenger Mechanisms for Mediating Intracellular Hormonal Functions Hormones That Act Mainly on the Genetic Machinery of the Cell Dr. Mahdi Noureddini

Hormone Receptors and Their Activation 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. Dr. Mahdi Noureddini

The Number and Sensitivity of Hormone Receptors Are Regulated The Number and Sensitivity of Hormone Receptors Are Regulated. (down and up -regulation ) This down-regulation of the receptors :decreases the target tissue’s responsiveness to the hormone 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, (5) decreased production of the receptors. up-regulation of receptors and intracellular signaling proteins. When this occurs, the target tissue becomes progressively more sensitive to the stimulating effects of the hormone. Dr. Mahdi Noureddini

Intracellular Signaling After Hormone Receptor Activation Ion Channel–Linked Receptors. G Protein–Linked Hormone Receptors. Enzyme-Linked Hormone Receptors. leptin receptor Intracellular Hormone Receptors and Activation of Genes. ( adrenal and gonadal steroid hormones, thyroid hormones, retinoid hormones,and vitamin D) Dr. Mahdi Noureddini

Protein &Polypeptide and Amine Hormone Receptors Surface receptor Hormone binds Transduction Enzyme activation Open channels Second messenger systems Synthesis Dr. Mahdi Noureddini Figure 7-5: Membrane receptors for peptide hormones

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Types of receptors Dr. Mahdi Noureddini

Adenylyl Cyclase–cAMP The Cell Membrane Phospholipid Second Messenger Mechanisms for Mediating Intracellular Hormonal Functions Adenylyl Cyclase–cAMP The Cell Membrane Phospholipid Calcium-Calmodulin Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Signal transduction mechanisms of hormones Activation of adenylate cyclase   Inhibition of adenylate cyclase Increased phospho-inositide turnover Tyrosine kinase activation b-adrenergic a2-adrenergic a1-adgrenergic Insulin LH, FSH, TSH, hCG Opioid Angiotensin II Growth factors (PDGF, EGF, FGF, IGF-1 Glucagon Muscarinic cholinergic – M2 Muscarinic cholinergic – M3 Growth hormone Vasopressin- V2 Vasopressin –V1 Prolactin ACTH Dr. Mahdi Noureddini

Hormones That Act Mainly on the Genetic Machinery of the Cell Steroid Hormones Increase Protein Synthesis Thyroid Hormones Increase Gene Transcription in the Cell Nucleus Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Steroid Hormones: Structure and Action Figure 7-7: Steroid hormone action Dr. Mahdi Noureddini

Measurement of Hormone Concentrations in the Blood Radioimmunoassay Enzyme-Linked Immunosorbent Assay (ELISA) Dr. Mahdi Noureddini

Dr. Mahdi Noureddini

Dr. Mahdi Noureddini