Introduction to Endocrine Physiology PDF

The Endocrine Physiology Introduction to Endocrinology Dr. Khalid Alregaiey Endocrine System: Overview Endcocrinology: It is study of homeostatic functions of substances called HORMONES, that are released from glands called endocrine glands distributed throughout the body....

The Endocrine Physiology Introduction to Endocrinology Dr. Khalid Alregaiey Endocrine System: Overview Endcocrinology: It is study of homeostatic functions of substances called HORMONES, that are released from glands called endocrine glands distributed throughout the body. Hormones: Are secretions of ductless glands that are directly released into the blood stream. They can act on cells in the vicinity or on distant target cells. Endocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormones Endocrine System: Overview Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus The pancreas and gonads produce both hormones and exocrine products The hypothalamus has both neural functions and releases hormones Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart The Endocrine System Autocrines and Paracrines Autocrines – chemicals that exert their effects on the same cells that secrete them Paracrines – locally acting chemicals that affect cells other than those that secrete them These are not considered hormones since hormones are long-distance chemical signals Types of Hormones Amino acid based – most hormones belong to this class, including: Amines (Tyrosine: Caecholamines and Thyroid hormones, Tryptophan: Melatonin) Polypeptide hormones protein hormones Steroids – Derived from Cholesterol, gonadal and adrenocortical hormones Fatty acid derived: Eicosanoids, derived from arachidonic leukotrienes and prostaglandins A Structural Classification of Hormones Correlation of Plasma Half-Life & Metabolic Clearance of Hormones with Degree of Protein Binding Hormone Protein Plasma half-life Metabolic clearance binding (%) (ml/minute) Thyroid Thyroxine 99.97 6 days 0.7 Triiodothyronine 99.7 1 day 18 Steroids Cortisol 94 100 min 140 Testosterone 89 85 min 860 Aldosterone 15 25 min 1100 Proteins Thyrotropin little 50 min 50 Insulin little 8 min 800 Antidiuretic hormone little 8 min 600 MCR = (mg/minute removed)/(mg/ml of plasma) = ml cleared/minute Circulating Transport Proteins Principle Hormone Transport Protein Transported Specific Corticosteroid binding globulin Cortisol, aldosterone (CBG, transcortin) Thyroxine binding globulin (TBG) Thyroxine, triiodothyronine Sex hormone-binding globulin Testosterone, estrogen (SHBG) Nonspecific Albumin Most steroids, thyroxine, triiodothyronine Transthyretin (prealbumin) Thyroxine, some steroids Determinants of Free Hormone Receptor Binding Carrier-bound hormone Endocrine Free Hormone cell Hormone receptor Hormone Biological degradation effects Hormone Action Hormones alter target cell activity by one of the following mechanisms: Ion Channel–Linked Receptors. G Protein–Linked Hormone Receptors. Enzyme-Linked Hormone Receptors. Intracellular Hormone Receptors and Activation of Genes (steroid and thyroid hormones) Hormone Action Hormones circulate to all tissues but only activate cells referred to as target cells Target cells must have specific receptors to which the hormone binds Location of receptors: 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 Cyclic Adenosine Monophosphate (cAMP) Second Messenger Mechanism Hormone (first messenger) binds to its receptor, which then binds to a G protein The G protein is then activated as it binds GTP, displacing GDP Activated G protein activates the effector enzyme adenylate cyclase Adenylate cyclase generates cAMP (second messenger) from ATP cAMP activates protein kinases, which then cause cellular effects Cyclic Adenosine Monophosphate (cAMP) Second Messenger Mechanism Cell Membrane Phospholipid: Second Messenger System Hormone binds to the receptor and activates G protein G protein binds and activates a phospholipase enzyme Phospholipase splits the phospholipid PIP 2 into diacylglycerol (DAG) and IP3 (both act as second messengers) DAG activates protein kinases; IP triggers 3 release of Ca2+ stores Ca2+ (third messenger) alters cellular responses Cell Membrane Phospholipid: Second Messenger System Cytokine Receptors & Tyrosine Kinase Receptors The Insulin Receptor & Mechanisms of Insulin Action Protein Hormones - Mechanisms of Action Tyrosine Adenylyl Cyclase Phospholipid Guanylate Cyclase Kinase/Cytokine Mechanism Mechanism Mechanism Receptor Mechanism ACTH GnRH ANP Insulin LH TRH IGF-1 FSH PTH GH TSH Angiotensin II Prolactin GHRH ADH (V1 receptor) Somatostatin Oxytocin ADH (V2 receptor) HCG MSH CRH Calcitonin PTH Glucagon Steroid and Thyroid Hormones Steroid hormones and thyroid hormone diffuse easily into their target cells Once inside, they bind and activate a specific intracellular receptor The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein This interaction prompts DNA transcription to produce mRNA The mRNA is translated into proteins, which bring about a cellular effect Steroid & Thyroid Hormones - Mechanism of Action Target Cell Activation Target cell activation depends on three factors Blood levels of the hormone Relative number of receptors on the target cell The affinity of those receptors for the hormone Up-regulation – target cells form more receptors in response to the hormone Down-regulation – target cells lose receptors in response to the hormone Hormone Concentrations in the Blood Hormones circulate in the blood in two forms – free or bound Steroids and thyroid hormone are attached to plasma proteins Hormone Concentrations in the Blood Concentrations of circulating hormone reflect: Rate of release Speed of inactivation and removal from the body Hormones are removed from the blood by: Degrading enzymes The kidneys Liver enzyme systems Interaction of Hormones at Target Cells Three types of hormone interaction Permissiveness – one hormone cannot exert its effects without another hormone being present Synergism – the total effect of two hormones together is greater than the sum of their individual effects Antagonism – one or more hormones opposes the action of another hormone Hormonal Rhythms 12 GH (G/L) PLASMA 8 4 0 8 12 16 20 0 4 8 500 400 CORTISOL PLASMA (nmol/L) 300 200 100 0 8 12 16 20 0 4 8 CLOCK TIME Control of Hormone Release Blood levels of hormones: Are controlled by negative and positive feedback systems Vary only within a narrow desirable range Hormones are synthesized and released in response to humoral, neural, and hormonal stimuli Feedback Control Negative feedback is most common: for example, LH from pituitary stimulates the testis to produce testosterone which in turn feeds back and inhibits LH secretion Positive feedback is less common: examples include LH stimulation of estrogen which stimulates LH surge at ovulation Feedback Mechanisms Negative Feedback Positive Feedback + + Target Endocrine Target Endocrine cell cell cell cell _ + Biological effects Biological effects Negative feedback Measurement of Hormone Concentrations Radioimmunoassay (RIA) Enzyme-Linked Immunosorbentm Assay (ELISA)