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Endocrinology and Reproduction

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Endocrinology and Reproduction Elisabet Stener-Victorin, Professor, PhD Reproductive Endocrinology and Metabolism (REM) group Department of Physiology and Pharmacology Karolinska Institutet, Stockholm, Sweden [email protected] General Consepts of Endocrine Control Hormone – Greek hormaein = ”excite” . Autocrine signalling e.g. interleukin-1 in lymphocytes . Paracrine signalling e.g. growth and clotting factors . Endocrine signalling all circulating hormones Classical Endocrine Organs Other ”non-classical” hormone glands e.g. CNS . Kidney . Stomach . Small intestine . Skin . Heart . Lung . Placenta Katch et al Essentials of Exercise Physiol. Figure 12.1 Hormones Controls and Regulates . Reproduction including gamete production, fertilization, nourishment of the embryo and fetus . Growth and development . Regulates ion and water balance . Regulates cellular metabolism and energy balance . Mobilize the immun system by responding to infection, trauma, and emotional stress Homeostasis . Maintance of steady states by coordinated physiological mechanisms . Contributes to homeostasis by controlling availablity of substrates and metabolism . Regulating body fluid and ion balance Homeostasis – like thermostat in the room Body temperature ~ 37ºC Blood glucose 4.4 – 6.1 mM Ca2+ 4.1 – 5.2 mg/dL Phosphate 0.8 – 1.5 mM How is homestasis achived? Endocrine system : 1. Gland 2. Hormone - receptor 3. Target organ - response Katch et al Essentials of Exercise Physiol. Figure 12.2 Principles for Feed-back Negative Positive (rare) Endocrine Endocrine cell cell A A Target Target Endocrine Endocrine cell cell B B Biological effect Biological effect Principles for Feed-back and Biorythm Complex multilevel . Long feedback loop Hypo- thalamus . Active hormone regulates the hypothalamus Releasing . Short feedback loop hormone . Active hormone regulates pituitary Anterior pituitary Target hormone Target Biorytm - Pulsatile release Endocrine . Circadian rythm (cortisol) cell Endocrine cell hormone . Monthly rythm (female sex hormones) . Life rythm (growth hormone) Biological effect Hypothalamus –”the boss” functional connections Fysiologi, Lännergren, Westerblad, Ulfendahl, Lundeberg och Studentlitteratur 2012. Fig. 4.4 Hormone classes . Three main types of hormones: . Amines - Tyrosine derivatives . Peptides . Steroids 1. Amine hormones . Derives from one or two amino acids . Eg. Norepinephrine, thyroid hormones . Water soluble → hydrophobic → receptor in the cell membrane . Bind to G-coupled membrane receptors → modulates second messengers 2. Peptide-derived hormones . Peptides = Proteins . E.g. insulin and glucagon → synthesized by ribosomes as pro-hormones . Water soluble → hydrophobic → receptor in the cell membrane . Bind to G-protein coupling receptors → modulates second messengers Amine and Peptide-derived hormone receptor location 3. Steroid hormones . All derives from cholesterol . Non-water soluble → Hydrophobic . Two main types of receptors: . Steroid receptors bind to receptor in cytosol and translocate to the nucleus . Thyroid receptors bind to the receptor directly in the nucleus . Steroid hormones e.g. Cortisol and aldosterone . Estrogen progesterone and testosterone Steroid hormone receptor location Steroid and thyroid hormone transport . Approx 90% bound to plasma proteins . Only the free hormone that is biological active . Free hormone and carrier-bound hormone – dynamic equilibrium Transport protein Principle hormone(s) transported Specific Corticosteroid-binding protein (transcortin) Cortisol, aldosterone Thyroxid-binding globulin Thyroxin, triiodothyronine Sex hormone-binding globulin Testosterone, estrogen Nonspecific Serum albumin Most steroids, thyroxin, triiodothyronine Transthyretin (prealbumin) Thyroxin, some steroids Mechanisms of hormonal transport and bioavailability . Circulating hormone concentration → synthesis and secretion . Protein binding – free vs bound . Only free hormones has an effect, be eliminated, and exert feed back regulation . Local enzymes in the tissue . Converts e.g. testosterone to the more potent form: DHT . Inactivates of e.g. cortisol in the kidney . Pulsatility . E.g. cortisol . Type of receptors Hypothalamus – “the boss” . Part of the limbic system . Control hormonal release from pituitary . Neuroendocrine and endocrine control: . Posterior pituitary (neuro) . Anterior pituitary (adeno) Hypothalamus Regulates basal body functions: . Biorhythms (suprachiasmatic nucleus) . Body temperature . Sleep . Defense – alarm – fear – aggressively . Growth . Reproduction and behavior . Delivery . Thirst (osmoreceptors) . Urine (osmoreceptors and antidiuretic hormone, ADH) . Appetite – target organ for leptin . Basal metabolic activity (thyroid releasing hormone) Posterior Pituitary (neurohypophysis) . Oxytocin → synthesized in paraventricular nucleus . Stimulates milk secretion . Stimulates uterine contractions during delivery . Arginine vasopressin = antidiurethic hormone (ADH) → synthesized in supratoptic nucleus . Regulates blood volume . ADH secretion regulated by hypothalamic osmorecetors . Main effect of ADH – decrease water excretion and increase water absorption in the kidney Källa: Netter. Atlas of Human Anatomy. Ciba-Geigy 1989 Anterior pituitary - adenohypophysis Hypothalamic neurons synthesize Hypothalamus GHRH, GHIH, TRH, CRH, GnRH, PIH. Anterior lobe Superior of pituitary hypophyseal artery GH, TSH, ACTH, FSH, LH, PRL Marieb E, N., Hoehn, K. Human anatomy and Physiology Figure 16.4c © 2013 Pearson Education, Inc. Anterior pituitary – Feed-back loops Katch et al Essentials of Exercise Physiol. Figure 12.4 Quizz https://create.kahoot.it/details/endocrinology-introduction-eng/f143a0e5-7ebb- 470f-976a-43123eb83d56 Students: . Login to Kahoot.it . Write pin code https://www.khanacademy.org/science/health-and-medicine/human-anatomy-and- physiology/reproductive-system-introduction/v/welcome-to-the-reproductive-system Hormone release and homeostasis . Hypothalamus . Pituitary . Growth hormone . Thyroid . Adrenal gland . Pancreas . Gonades (ovary/testis) Marieb E, N., Hoehn, K. Human anatomy and Physiology Figure 16.1 Regulation of anterior pituitary hormones Growth Hormone (GH) → IGF-1 . GH stimulates body growth . Important for normal body development . Metabolic effects . Protein synthesis → increase amino acid transport into cells, enhance DNA and RNA transcription, RNA translation of protein and decrease protein and amino acid catabolism . Increase blood glucose → Glycogenolys (glucose production by breakdown of glycogen), increased gluconeogenesis and insulin production (similar to type 2 diabetes) . Decrease glucose uptake in muscle and adipose tissue . Lipolysis (break down of fat cells) → increase concentrations of fatty acids Growth Hormone axis • GH has a pulsatile secretion pattern • Max secretion during the first h of sleep • GH peak late puberty • Adulthood - ↓ pulsatile burst, no change in number of pulses Growth Hormone Regulation Hypothalamus secretes growth Feedback Inhibits GHRH release Stimulates GHIH hormone—releasing Anterior release hormone (GHRH), and pituitary Inhibits GH synthesis somatostatin (GHIH) and release Growth hormone Indirect actions Direct actions (growth- (metabolic, promoting) anti-insulin) Liver and other tissues Produce Insulin-like growth factors (IGFs) Effects Effects Carbohydrate Skeletal Extraskeletal Fat metabolism Increases, stimulates Increased protein Reduces, inhibits Increased cartilage Increased Increased blood synthesis, and formation and fat breakdown glucose and other Initial stimulus cell growth and skeletal growth and release anti-insulin effects Physiological response proliferation Result Other Hormones Affecting Growth Hormone release and homeostasis . Hypothalamus . Pituitary . Growth hormone . Thyroid . Adrenal gland . Pancreas . Gonades (ovary/testis) Marieb E, N., Hoehn, K. Human anatomy and Physiology Figure 16.1 Regulation of anterior pituitary hormones Thyroid Hormone (TH) . Two related compounds . T4 (thyroxine); has 2 tyrosine molecules + 4 bound iodine atoms . T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms . Plays a role in: . Maintenance of blood pressure . Regulation of tissue growth . Development of skeletal and nervous systems . Reproductive capabilities Action of Thyroid hormones . Metabolic Actions . Permissive Actions – on catecholamine's by increasing synthesis of β-adrenergic receptors . Growth and Development Low thyroid hormones High thyroid hormones Basal metabolism ⇓ ⇑ Carbohydrate metabolism ⇓ Gluconeogenesis ⇑ Gluconeogenesis ⇓ Glycogenolys ⇑ Glycogenolys Glycogenolys = breakdown of glycogen Protein metabolism ⇓ Synthesis ⇑ Synthesis ⇓ Proteolysis ⇑ Proteolysis Gluconeogenesis = generation of glucose from Lipid metabolism ⇓ Lipogenes ⇑ Lipogenes substrates like pyrovate, lactate, glycerol and ⇓ Lipolys ⇑ Lipolys glucogenic amino acids ⇑ Serum cholesterol ⇓ Serum cholesterol Thermogenes ⇓ ⇑ .Thyroid hormones increases metabolic rate and heat production .↑ Mitochondria .↑ blood flow, heart rate, and cardiac output .↑ Respiration .↑ Expression of NA+/K+ ATPase → ↑ neural signaling → muscle tremor (hyperthyroidism) Parathyroid Glands and Parathyroid Hormone . Embedded in the posterior aspect of the thyroid . Contain cells that secrete parathyroid hormone (PTH) . PTH—most important hormone in the calcium (Ca2+) homeostasis . Calcium function – Necessary for: Structural: Bone, teeth, connective tissue Muscle contraction Blood clotting Nerve impulse transmission and stability of excitable membranes
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