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Human Endocrine System

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Human Endocrine System Human Endocrine System Dr. L K Dwivedi Department of Biomedical Sciences, Bundelkhand University, Jhansi Endocrine and hormone •Endocrine system communicates to distant tissues through bloodblood""""carriedcarried chemicals. •Organs included in the endocrine system are adrenal, gonads, hypothalamus, pancreas, parathyroid, pituitary, thyroid, etc. Nervous Vs Endocrine system Nerves in the posterior pituitary release Oxytocin and Antidiuretic hormone, which act on the breast and kidneys, respectively; Nerves release epinephrine from the adrenal medulla, which acts on the heart, skeletal muscle, and the liver; The hypothalamic nerves secrete chemicals (releasing hormones) that act on the anterior pituitary to cause hormone release. Therefore, the definition of the endocrine system should also include such neuroendocrine systems. The hormone The hormones areareare chemical substances produced bybyby specialized tissues and secreted into blood, ininin which they arearearecarried tototo target organs and triggers specific biological functionsfunctions" """Starling and BaylissBayliss. ... Moreover, AAAhormone isisis aaa chemical nonnon" """nutrient,nutrient, intercellular messenger that isisis effective atatat micromolar concentrations orororless (high efficiency)efficiency). ... Concentration Peptidal hormone ininin animal blood 101010 """12"121212 101010 """10"101010 MMM Steroid hormone ininin animal blood 101010 """10"101010 –––101010 """8"888MMM.M... ENDOCRINE GLAND HORMONES SECRETED TISSUE EFFECT Hypothalamus Corticotropin-releasing hormone (CRH) Stimulates ACTH secretion Dopamine Inhibits prolactinsecretion Gonadotropin-releasing hormone (GnRH) Stimulates LH and FSH secretion Growth-hormone releasing hormone (GHRH) Stimulates GH secretion Somatostatin Inhibits GH secretion Thyrotropin-releasing hormone (TRH) Stimulates TSH and prolactin Anterior Pituitary Adrenocorticotropic hormone (ACTH) Stimulates synthesis/secretion of cortisol , androgens and aldosterone Anterior Follicle- stimulating hormone (FSH) Stimulates sperm maturation; development of ovarian follicles Growth hormone (GH) Stimulates protein synthesis and growth Luteinizing hormone (LH) Stimulates testosterone, estrogen, progesterone synthesis; stimulates ovulation Melanocyte-stimulating hormone (MSH) Stimulates melanin synthesis Prolactin Stimulates milk production Thyroid-stimulating hormone (TSH) Stimulates thyroid hormone synthesis/secretion Posterior Pituitary Oxytocin Stimulates milk ejection and uterine contraction ENDOCRINE GLAND HORMONES SECRETED TISSUE EFFECT Posterior Pituitary Antidiuretic hormone (ADH) Stimulates renal water reabsorption Thyroid Triiodothyronine (T3) and Stimulates growth, oxygen consumption, heat production, thyroxine (T4) metabolism Calcitonin Decreases blood Ca concentration Parathyroid Parathyroid hormone (PTH) Increases blood Ca concentration Adrenal cortex Cortisol Increases glucose synthesis, mediates “stress ” response Aldosterone Increases renal reabsorption of Na +, secretion of K +, and H+ Androgens Similar to testosterone but weaker Adrenal medulla Epinephrine Stimulates fat and carbohydrate metabolism Pancreas Insulin Decreases blood glucose levels; anabolic effects on lipid and protein metabolism Glucagon Increases blood glucose levels Testes Testosterone Stimulates spermatogenesis and secondary sex characteristics Ovaries Estradiol Stimulates growth/development of female reproductive system and breasts, follicular phase ofmenstrual cycle, prolactin secretion, and maintains pregnancy Progesterone Luteal phase of menstrual cycle and maintains pregnancy Corpus luteum Estradiol and progesterone As above Placenta) Human chorionic gonadotropin Stimulates estrogen/progesterone synthesis by corpus luteum (hCG Endocrine System Chemical Nature of Hormones Harmone have paracrine and autocrine functions. Hormones are divided into four groups based on chemical structure: 1. Amines ，(come from the amino acid tyrosine), 2. Peptides ，(less than 20 amino acids), 3. Small proteins ，(more than 20 amino acids), 4. Steroids ，(come from cholesterol). Hormones act through specific receptors that define tissue selectivity and response. Receptors for amine, protein, and peptide hormones are located on the cell membrane, while those for steroid and thyroid hormones are within the cell. Membrane receptors are of four types based on their signaling mechanisms: G protein, tyrosine kinase, guanylyl cyclase, cytokine family. Steroid and thyroid hormones act through nuclear receptors that stimulate gene expression. Membrane-receptor mediated hormones elicit rapid (minutes) cellular responses; nuclear-receptor mediated hormones elicit slow (hours), long lasting cellular responses (because of slow protein degradation). Communication of the hormones Telecrine signals Neurocrine signals Components of membrane receptors Carbohydrate group of glycoprotein Receptor of Outside cell transmembrane 7 times Cell membrane Inside cell Combining position of phosphorylation Membrane receptors consist of three components: (1) an extracellular domain that binds the hormone; (2) a transmembrane domain that anchors it in the membrane; (3) an intracellular domain that couples the receptor to an intracellular signaling system. Receptor Receptor Enzyme Signal conductive mechanism of G-protein linked membrane receptors GGG"G"""proteinprotein linked receptors have the characteristic of being linked to an intracellular class of proteins called G proteins. G proteins are a cluster of three proteins (subunits) that, when activated by hormone binding to the extracellular domain of the receptor, cause stimulation of one of two enzymes, adenylyl cyclase (AC) or phospholipase C ... Activation of AC leads to the formation of cyclic adenosine monophosphate (cyclic AMP, cAMP) ,,, and activation of phospholipase C leads to the formation of inositol trisphosphate (IP 333))) or diacylglyercerol (DAG or DG) ,,, or activation of protein kinase C (PKC) . These named second messenger molecules initiate a cascade of events culminating in the hormone response. Theory of the second messengers for G-protein coupled receptor Cell membrane Hormone Physiological and Biochemical Functions Hormone Inactive protein Protein phosphorylation AC kinase Glycogen decomposition Adenylyl cyclase Adenylyl Fat decomposition Steroid Hormones synthesis Second Active protein Histone-nucleic acid synthesis Hormone Messenger kinase Nuclein-protein synthesis Membrane protein-membrane permeability AC: Adenylyl cyclase; Canaliculus secreted movement R: regulative part in the receptor; C: part for reaction Principle of hormone acting on membrane receptor Effects of Guanylyl Cyclase (GC) Receptors The guanylyl kinase receptors (on the membrane, combined with ANP) have the enzyme guanylyl cyclase as a portion of their intracellular domain. Binding of hormone to the extracellular domain leads to activation of guanylyl cyclase and the formation of cyclic guanosine monophosphate (cyclic GMP or cGMPcGMP)))). This second messenger initiates the hormone response. Effects of Tyrosine Kinase (TK) Receptors The tyrosine kinase receptors are distinguished by having an intracellular domain that phosphorylates proteins on specific tyrosine molecules. These tyrosinetyrosine""""phosphorylatedphosphorylated proteins act as second messengers to initiate a cascade of events leading to hormone response. Mechanisms of hormone acting on membrane receptors (summing-up) Effects of Steroid and Thyroid Hormones Steroid and thyroid hormones (primarily TTT 333)))signal through intracellular receptors, which actactact solely tototo initiate gene expressionexpression. ...Both hormone types diffuse through thethethe cell membrane tototo actactact ononon their intracellular receptorsreceptors....The receptors areareare protein molecules that bind tototo specific DNA sequences known asasas hormone response elementselements. ... The hormonehormone- ---receptorreceptor complex activates thethethe HRE, initiating DNA transcription leading tototoprotein synthesissynthesis. ... Mechanism of Steroid Hormones Effect Mechanisms of T3 and T4 Effects Synthesis of hormones Peptide and protein hormones are synthesized from amino acids as prohormones or preprohormonespreprohormones,, which are subsequently modified and stored in intracellular vesicles until secreted by exocytosisexocytosis.. (Rough ER) Amine and steroid hormones are synthesized from precursor molecules (tyrosine, cholesterol) present in the blood. Thyroid and steroid hormones are not stored in secretory vesicles, but the amine hormone epinephrine is. Control of hormone secretion (Common Mechanism) Humoral regulation Short feedback Solid line means positive feedback; Broken line represents negative feedback Super short feedback Long feedback Other mechanisms: biological rhythmic secretion; nervoue regulation, etc. Hormone Transport in the Blood Amine, peptide, and small protein hormones circulate in a free form in blood because they are water soluble. Steroid and thyroid hormones are carried in the blood bound to proteins (as carrier, e.g. albumin) because they are water insoluble. Protein binding reduces hormones loss through the kidney since the proteinprotein--hormonehormone complex cannot be filtered. Only the free form of the hormone can stimulate tissue receptors because of the capillary endothelium permeability. Most hormones are removed from the blood by the liver and kidney shortly after being secreted even though their tissue effect continues (half(half--lifelife
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