Hypothalamo-hypophysial tract Diencephalon : Thalamus + hypothalamus 1
Function of Hypothalamus Autonomic (Sy. Parasy.) Cardiovascular, GI, urinary tract Regulation of adenohypophysis Secretion of hormones of neurohypophysis Regulation of nutrition/energy Hunger, satiety, body mass Metabolic rate Regulation of water balance/blood volume Input: thirst =>fluid intake Output: urine volume Instinctual behaviors Defense behavior Offensive/aggressive behavior Sexual behavior Circadian rhythms Sleep/wake Thermoregulation Respiration Afferentation: Periphery, cereberal cortex, own receptors Efferentation: Neural: somatic, autonomic Hormonal Role of Hypothalamus Neuroendocrine control Catecholamines Afferents: Limbic areas Integrating areas: Dorsal and posterior hypothalamus Vazopresszin: Afferents: osmo- volumen-, baroreceptorok Integrating areas: Supraoptic, paraventricular nuclei Oxytocin: Afferents: Touch receptors in breast, uterus genitalia Integrating areas: Supraoptic, paraventricular nuclei TRH/TSH : Afferents: Thermoreceptors Integrating areas: Paraventricular nuclei ACTH/CRH : Afferents: limbic areas, reticular formation; cortisol; suprachiasmatic nucl. Integrating areas: Paraventrikular nuclei FSH-LH/GnRH Afferents: estrogen, sensory (skin, genitalia), visual stimuli Integrating areas: Preoptic area Prolactin/PIH/PRH Afferents: Touch receptors in breast Integrating areas: Arcuate nucl. GH (growth hormone)/somatostatin-grh Afferents:? Integrating areas: Arcuate and periventricular nucl. 2
Role of Hypothalamus Thermoregulation: Afferents: thermoreceptors: skin, deep tissue, spinal cord, hypothalamus Integrating areas: Anterior hypothalamus: cooling Posterior hypothalamus: heating Appetitive behavior: Thirst Afferents: Osmoreceptors, angiotensin II Integrating areas: Lateral superior hypothalamus Hunger Afferents: Glucostat cells, leptin receptors, etc. Integrating areas: Ventromedial, arcuate, paraventricular nuclei, lateral hypothalamus Sexual behavior Afferents: estrogen and androgen sensitive cells Integrating areas: anterior ventral hypothalamus Role of Hypothalamus Defensive reactions (fear, rage) Afferents: Sense organs, neocortex Integrating areas: Diffuse in the hypothalamus, limbic system Body rhythms Afferents: Retina => retinohypothalamic pathway Integrating area: Suprachiasmatic nucl. 3
Anatomy of hypophysis anterior lobe, pars intermedia, posterior lobe 4
Portal hypophysial vessels Hormones of adenohypophysis: ACTH (adrenocorticotropic hormone), peptid TSH (thyroid-stimulating hormone), glycoprotein FSH (follicle-stimulating hormone), glycoprotein LH (luteinizing hormone), glycoprotein Prolactin, protein, GH (growth hormone), protein 5
Regulation of adenohypophysis by hypothalamus Paraventricular nucl.(somatostatin, CRH, TRH), preoptic area (GnRH), arcuate nucl. (GHRH, dopamine), dorsomedial nucl.(prh) Hypophysiotropic hormones: Releasing: CRH (corticotropin-releasing hormone), GHRH (growth hormone-releasing hormone), GnRH (gonadotropin-releasing hormone), TRH (thyreotropin-releasing hormone) [PRH (prolactin releasing hormone)] Inhibiting: dopamine (PRL, FSH, LH,TSH), somatostatin (TSH, GH) The role of hypothalamus: rythmicity, pulsating release Regulation of adenohypophysis By negative feedback T3, T4, cortisol, IGF1: insulin-like growth factor Estrogen, progesteron, inhibin, follistatin, androgens By positive feedback Activin, estrogen 6
MSH Hormone of pars intermedia 7
Secretion of hormones of neurohypophysis by hypothalamus Supraoptic and paraventricular nuclei Antidiuretic hormone (ADH) (vasopressin) Oxytocin Peptide (39 AA) 1. ACTH Origin from proopiomelanocortin (POMC) 8
Action mechanism: GPR => camp Regulation: Stress CRH ADH Cortisol ACTH Daily rhytm (highest level at morning) Effects: Activation of adrenal cortex => secretion of cortisol, androgens and aldosterone. 9
Glycoprotein 2. TSH Action mechanism: GPR (camp ) Regulation: TRH (cold?) somatostatin dopamine T3, T4 Effects: Activation of the thyroid gland => T3, T4 10
III. Regulation of hormone secretion Permanent cold + Birth Excess calory intake Leptin, MSH Low circadian Rhytm Max: early morning Min: afternoon Neural Growth factors + Hypothalamus TRH (tripeptide) Portal circulation Adenohypohysis TSH T 3 és T 4 Permanent stress Fasting (AgRP) Warmth Cortisol Dopamin, somatostatin High amount of Iodine Inhibitors of synthesis 3. FSH 4. LH Glycoprotein Action mechanism : GPR (camp ) Regulation: GnRH ; dopamine estrogen, ; progesterone ; inhibin, ; follistatin Activin Functions: FSH: development of collicle => estrogen secretion male: spermiogenesis LH: ovulation, corp. Luteum => progesterone, estrogen secretion Male: testosteron synthesis Sexual function during life: Fetal life: 80-150 th days: pulsating GnRH secretion => FSH, LH 150-280. days: low level of GnRH Newborn - 12 month: GnRH secretion Until puberty: small GnRH Puberty menopausa: pulsating GnRH Menopausa: high level non-pulsating GnRH => low level of FSH, LH 11
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5. Prolactin Protein Action mechanism: TRK-receptor Regulation: inhibition by dopamine Facilitation by estrogen, TRH, PRH Pregnancy Nursing Breast stimulation Effects of prolactin Milk secretion (production), Sleep regulation, GnRH inhibition Establishment of maternal behavior Daily rythm (max: night, min: at noon), Pulsation 13
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Melanocyte-stimulating hormone (α-msh) Peptide (13 AA) Origin: POMC (proopiomelanocortin) Rudimentary in humans (NO hormone?) Action mechanism Melanocortin receptor 1 (GPR: camp ) (ACTh also activates this receptor in high doses) Effect: Melanocyte (melanin synthesis ) Protein metabolism: liver Action mechanism: 6. Growth hormone (GH) Activation of GH receptors (enzyme-linked and GPR) Through IGF-I (insulin-like growth factor) 15
GH-receptor Cytokine receptor Transzmembrane glykoprotein 2 binding sites of GH for receptor dimerization Activation of cytoplasmic Janus kinases Modulation of gene expression Effects: Basal metabolism (15%) Chondrogenesis in cartilaginous epiphysial plates => epiphysial growth =>increased length (stature) IGF secretion from liver Increase of viscera and muscle ACTH-like effects: adrenal cortex Androgen-like effects: increase of genitalia Se. phosphate level Se urea, aminoacid levels Increased red blood cell production Increased Calcium intestinal absorption Descresed Na +, K + excretion in the urine (Na + retention) 16
Effects: Metabolism: Protein metabolism: anabolism, positive nitrogen balance Carbohyrate metabolism: Increased blood glucose level (diabetogenic) It increases hepatic glucose output It exerts anti-insulin effect in muscle It decreases the number and sensitivity of insulin receptors It increases the sensitivity of pancreas to glucose => insulin secr. Fat metabolism: It increases the lipolysis => increased Se. FFA level => ketogenic effect 17
Regulation of GH secretion Hypothalamus: GHRH, somatostatin Stimuli that increase secretion: Deficiency of energy substrate: Hypoglycemia, exercise, fasting High level of certain amino acids Protein meal, infusion of arginine and some other amino acids Glucagon Stressful stimuli Pyrogen, ADH, various psychologic stresses (cerebral cortex) Going to sleep Estrogens and androgens Stimuli that decrease secretion: REM sleep Glucose Cortisol FFA GH/IGF 18
Physiology of growth GH/IGF-1 T3,T4 glucocorticoids estrogens androgens insulin genetic factors Nutrition: proteins, vitamins, minerals, calories 19
Rat continue growth Human Growth periods During fetal life: there is no need for GH After birth Two periods Infancy: T3, T4, GH, Late puberty: GH, androgens, estrogens The cause of cessation of growth: closure of epiphyses by gonadal hormones Sexual differences in growth The role of the hormones GH: Deficiency: In young people: dwarf (proportion characteristic), no sexual maturation In adults: decreased metabolism Overproduction. In young people: gigantism In adults: acromegaly 20
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T3,T4: permissive effect Ossification of cartilage Growth of teeth Contours of face Proportion of the body Deficiency: cretin Inzulin: permissive effect Sexual hormones: Importance at puberty Ossification of epiphysial cartilage Glucocorticoids: permissive effect 22
Neurohypophysis Hormones: only storage in hypophysis ADH (vasopressin) Oxytocin Hormone production: hypothalamus Supraoptic, Paraventricular nuclei 23
ADH Antidiuretic hormone (vasopressin) Nonapeptide Action mechanism GPR V1: IP3/DAG V2: camp Effects: Kidney: V2 receptor: Aquaporin2/urea transzporter integration into the membrane => permeability to water/urea => water/urea reabsorption => osmolarity of renal medullary insterstitial fluid (1200 mosm/l) Blood vessels: V1 receptor: vasoconstriction (filtration ) Deficiency: Diabetes insipidus 24
Changes in osmolarity of the tubular fluid as it passes through the different tubular segments in the presence of high levels of antidiuretic hormone (ADH) and in the absence of ADH. Action mechanism of ADH 25
Regulation of ADH secretion Increase Inhibit Increased plasma osmolarity Decreased blood volume Decreased blood pressure Angiotensin II Nausea Hypoxia Pain Exercise Decreased plasma osmolarity Increased blood volume Increased blood pressure Alcohol 26
Hormonal control of osmolarity by ADH 27
Oxytocin (9 AA) Action mechanism: Metabotropic receptor => IP3/DAG => increased IC calcium level Effects Milk ejaculation reflex (myoephithel cell contraction) Uterus contraction (enhanced by estrogen, inhibited by progesterone) Luteolysis Increased time of ejaculation (contraction of vas deferens) Establishment of maternal behavior Learning, pain, memory 28
Regulation of secretion: Neuroendocrin reflex mechanism: mechanical stimuli (breast, genitalia) emotional stimuli in lactating women In late pregnancy the number of oxytocin receptors, and the secretion of oxytocin increase Stressful stimuli => increase Alcohol => decrease 29
Pineal gland Atrophy in adult 30
Hormone: melatonin (tryptophane derivative) Metabolism: liver Action mechanism: (metabotropic receptors) MT1 (camp ) és MT2 (PLC ) receptor Effects: (it lightens the skin of tadpole) It determines the circadian and sesonal rhythms It regulates sleep/wake rhythms It determines sexual development and activity Inhibition of the LH release Free radical scavenger antidepressant 31
Regulation of melatonin secretion Light stimuli (eye) ) => Hypothalamus (nucl. Suprachiasmatic) => Sympathetic fiber inhibition (Superior cervical ganglion); (beta1-receptor) => daily rhythms (highest level during night) (Blind people with free-running circadian rhythm) 32