ENDOCRINOLOGY Lec 2 Dr Ali albayati 6142021 1

ENDOCRINOLOGY Lec. 2 Dr. Ali al-bayati 6/14/2021 1

Introduction n n Endocrinology is the study of hormonally regulated conditions Endocrinology involves hormones from: Hypothalamus u Pituitary u Thyroid u Pancreas u Adrenals u Kidneys u Gonads u Smaller glands (Thymus, Pineal etc) u 6/14/2021 2

The Players Other endocrine organs • endothelial vascular cells Hypothalamus • adipocytes • heart • bone • liver • kidney • ? ? 6/14/2021 3

Definitio ns Endocrinology- study of the biosynthesis, n n storage, chemistry, and physiological function and abnormalities of hormones. The term hormone (hormao G = to excite) was first used by William M. Bayliss and Ernest H. Starling, who showed that a chemical substance (secretin) from the intestine could stimulate the action of a pancreatic secretion. These substances were then called as “chemical messengers” Went and Thiemann (1937) defined a hormone as “a substance which, produced in any one part of an organism, is transferred to another part and there influences a specific physiological process. ” 4 6/14/2021

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The endocrine system: is a series of glands that produce and secrete hormones that the body uses for a wide range of functions. These control many different functions, including: Respiration, Metabolism, Reproduction, Sensory perception, Movement, Sexual development and Growth. Characteristics of the Endocrine System; 1. Composed of glands that secrete hormones into the circulatory system. 2. Hormones are secreted in minute amounts into the interstitial space. 3. Hormones enter the circulatory system and arrive at specific target tissues. 4. Functions are similar to the nervous system. Differences; q Amplitude-modulated vs. Frequency-modulated q Response of target tissue to hormones is usually slower and of longer duration that to neurons. 6/14/2021 6

Based on their site on action, the hormones are of two types: local and general. The local hormones, have specific local effects, example; acetylcholine, secretin, cholecystokinin etc. The general hormones, secreted by specific endocrine glands and are transported in the blood to cause physiologic actions at points remote from their place of origin. A few of the general hormones affect almost all cells of the body, e. g. , growth hormones (GH) and thyroid hormones ; whereas other general hormones, however, affect specific tissues far more than other tissues, e. g. , adrenocorticotropic (a hormone secreted from adenohyprophysis and stimulating the adrenal cortex) and ovarian hormones (affecting the uterine endometrium). 6/14/2021 7

Functions of hormones 1. 2. 3. 4. Regulatory or homeostatic function. Permissive function Integrative function. Morphogenetic function. Classes of Hormones are classified by various criteria: 1. By Proximity of their site of synthesis to their site of action, 2. By their chemical structure, 3. By their degree of solubility in aqueous medium 6/14/2021 8

3 classes of hormones based on proximity of site of Synthesis to Site of Action: v Autocrine Hormones: those that act on the same cells that synthesize them; v Paracrine Hormones: those that are synthesized very close to their site of action; v Endocrine Hormones: those that are synthesized by endocrine glands and transported in the blood to target cells that contain the appropriate receptors; 6/14/2021 9

Four classes of hormones based on chemical structure: Most peptide hormones circulate unbound to other proteins 1. Peptides or Protein hormones: 2. Amino acid derivatives: • Adrenaline, Catecholamines, Thyroid Hormones 3. Fatty acid derivatives: half-life of circulating peptide hormones is only a few minutes Thyrotropin Releasing Hormone (TRH), made up of three amino acid residues; Insulin, made up of 51 amino acid residues; Pituitary Gonadotropins, made up of large Glycoproteins with subunits; • Eicosanoids, {prostaglandins, prostacyclins, leukotrienes and thromboxane}, • In contrast to hormones, prostaglandins usually act locally, affecting only adjacent cells or the very cell that secreted it. • rapidly inactivated by being metabolized, and are typically active for only a few seconds 4. Steroid hormones: ; Example: Estradiol, Testosterone, Cortisol. 6/14/2021 10

Two classes of hormones based on solubility in aqueous medium; 1. Hydrophilic Hormones (Lipophobic Hormones); 2. Lipophilic Hormones (Hydrophobic Hormones); 6/14/2021 11

Hormones’ Receptors and Target Cells Target tissue: - For a given hormone is a tissue contains specific receptor proteins that bind the hormone and initiate a cellular response • Receptors : - Are specific molecules within the cell membrane , cytoplasm or nucleus of the target cell that are necessary for recognition and binding of extra cellular messenger (hormone) Target tissue must have two characters in responce to the hormone Ø 1 -The tissue should recognize the hormone by a receptor. Ø 2 -The tissue should have intracellular capacity of translating the massage of the hormone to biochemical event or reaction. 6/14/2021 12

Regulation of target tissue activity. The hormones regulate the activities of their target tissues in two ways: 1 -By regulating the activities of already present proteins (enzymes) in the cells, this takes place rapidly within minutes. 2 -By regulating the synthesis or degradation of proteins, taking place more slowly requiring hours or days. 6/14/2021 13

• Hormones as a signal • Hormonal signaling involves the following: • 1 -Biosynthesis of a particular hormone in a particular tissue. • 2 -Storage and secretion of the hormone. • 3 -Transport of the hormone to the target cell(s). • 4 -Recognition of the hormone by an associated cell membrane or intracellular receptor protein. • 5 -Relay and amplification of the received hormonal signal via a signal transduction process: This then leads to a cellular response. • 6 -Degradation of the hormone. 6/14/2021 14

Interactions with receptors • Hormone-receptor complex concentrations are effectively determined by three factors: • 1 -The number of hormone molecules available for complex formation. • 2 -The number of receptor molecules available for complex formation. • 3 -The binding affinity between hormone and receptor 6/14/2021 15

Characteristics of Receptors 1. Hormone specificity Receptors can bind one hormone only. Agonists and antagonists can also bind the receptors. Many neurohormonal ligands and hormones can bind several different receptors usually within the same molecular family of receptors (i. e. epinephrine binds α 1, α 2, β 1, and β 2 adrenergic receptors). 2. Affinity: refers to the concentration of hormones required to activate sufficient receptors to trigger a biological effect. 3. Receptors number: 4. Tissue Specificity: The presence of the appropriate type of receptors in the respective tissue is essential for proper hormone function. 6/14/2021 16

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Two main type of hormone receptor pathways 1. Pathways Involving Intracellular Hormone Receptors (Group I) 2. Involving Cell Membrane Hormone Receptors (Group II) 6/14/2021 18

Intracellular Hormone Receptors Group I q Hormones that bind to this type of receptor must be able to cross the cell membrane. q Steroid hormones are derived from cholesterol and therefore can readily diffuse through the lipid bilayer q Thyroid hormones, which contain benzene rings studded with iodine, are also lipidsoluble and can enter the cell. q binding generates a hormone-receptor complex that moves toward the chromatin in the cell nucleus and binds to a particular segment of the cell’s DNA. 6/14/2021 19

Intracellular Hormone Receptors 6/14/2021 Group I 20

Structure of Intracellular Receptors When hormone binds to receptor, a characteristic series of events occurs: 1. Receptor activation is the term used to describe conformational changes in the receptor induced by binding hormone. The major consequence of activation is that the receptor becomes competent to bind DNA. 2. Activated receptors bind to hormone response elements, which are short specific sequences of DNA which are located in promoters of hormone-responsive genes. 3. Transcription from those genes to which the receptor is bound is affected. Most commonly, receptor binding stimulates transcription. 6/14/2021 21 The hormone-receptor complex thus functions as a transcription factor.

Thank you 6/14/2021 22