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Hypothalamo-hypophysial tract
Diencephalon : Thalamus + hypothalamus
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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• Thermoregulation:
– Afferents: thermoreceptors: skin, deep tissue, spinal cord, hypothalamus
– Integrating areas: • Anterior hypothalamus: cooling
• Posterior hypothalamus: heating
• Appetitive behavior:
• Thirst– Afferents: Osmoreceptors, angiotensin II, etc.
– 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, etc.
– Integrating areas: anterior ventral hypothalamus
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Role of Hypothalamus
• Defensive reactions (fear, rage)
– Afferents: Sensory organs, neocortex
– Integrating areas: Diffuse in the hypothalamus, limbic
system
• Body rhythms
– Afferents: Retina => retinohypothalamic pathway
– Integrating area: Suprachiasmatic nucl.
• 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
– Releasing factors:– TRH/TSH (prolactin) : Afferents: Thermoreceptors
• Integrating areas: Paraventricular nuclei
– CRH/ACTH: Afferents: limbic areas, reticular formation; cortisol; suprachiasmatic nucl.
• Integrating areas: Paraventrikular nuclei
– GnRH/FSH, LH Afferents: estrogen, sensory (skin, genitalia), visual stimuli
• Integrating areas: Preoptic area
– PRH/Prolactin Touch receptors in breast
• Integrating areas: Arcuate nucl.
– GRH/GH Afferents: ??
• Integrating areas: Arcuate and periventricular nucl.
– Inhibiting factors• Somatostatin (TSH, GH, prolactin)
• Dopamine (TSH, FSH, LH, prolactin)
Role of Hypothalamus
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Anatomy of hypophysis
– anterior lobe,
– pars intermedia,
– posterior lobe
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Portal hypophysial vessels
Hormones of adenohypophysis:
� ACTH (adrenocorticotropic hormone), peptid,
cAMP ↑
� TSH (thyroid-stimulating hormone),
glycoprotein, cAMP ↑
� FSH (follicle-stimulating hormone),
glycoprotein, cAMP ↑
� LH (luteinizing hormone), glycoprotein, cAMP
↑
� Prolactin, protein, TRK
� GH (growth hormone), protein, TRK
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Regulation of adenohypophysis
• by hypothalamus
– 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, prolactin)
• (Paraventricular nucl.(somatostatin, CRH, TRH), preoptic area
(GnRH), arcuate nucl. (GHRH, dopamine), dorsomedial
nucl.(PRH))
– 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
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Hormone of pars intermedia
Melanocite-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 ↑)
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Secretion of hormones of neurohypophysis by
hypothalamus
• Supraoptic and
paraventricular nuclei
– Antidiuretic hormone
(ADH) (vasopressin)
– Oxytocin
1. ACTH
• Peptide (39 AA)
• Origin from proopiomelanocortin (POMC)
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• 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
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Glycoprotein (210 AA)
Action mechanism:
GPR (cAMP↑)
Regulation:
TRH (cold?) ↑
somatostatin ↓
dopamine ↓
T3, T4 ↓
Effects:
– Activation of the thyroid gland => T3, T4 ↑
2. TSH
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3. FSH 4. LHGlycoprotein (FSH:210; LH:213 AA)
– Actionmechanism: GPR (cAMP ↑)
– Regulation:
• GnRH ↑; dopamine ↓
• estrogen, ↓ ↑; progesterone ↓; inhibin, ↓; follistatin ↓, androgens ↓,
• Activin ↑
– Functions:
• FSH: development of collicle => estrogen secretion ↑
• male: spermiogenesis
• LH: ovulation, corp. Luteum => progesterone, estrogensecretion ↑
• Male: testosterone synthesis ↑
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5. Prolactin
• Protein (199 AA)
• Action mechanism:
– Enzyme-linked receptor
• Regulation:
– inhibition by
• Dopamine, somatostatin
– Facilitation by
• estrogen,
• TRH,
• PRH
• Pregnancy
• Nursing
• Breast stimulation
• sleeping
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Effects of prolactin
• Milk secretion (production),
• GnRH inhibition
• Establishment of maternal behavior
• Sleep regulation,
Daily rythm (max: night, min: at noon),
Pulsation
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6. Growth hormone (GH)
• Protein
• metabolism: liver
• Action mechanism:
– Activation of GH receptors (enzyme-linked and GPR)
• Through IGF-I (insulin-like growth factor)
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GH-receptor
• Cytokine receptor
• Transzmembrane
glycoprotein
• 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)
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• Protein metabolism:
– Anabolism ↑
– Nitrogen balance: +
• Carbohyrate metabolism: blood glucose level ↑(diabetogenic)
– hepatic glucose output ↑
– It exerts anti-insulin effect in muscle
– Number and sensitivity of insulin receptors ↑
– Sensitivity of pancreas to glucose ↑ => insulin secr. ↑
• Fat metabolism: lipolysis ↑ => Se. FFA ↑ level => ketogenic effect
Effects: Intermedier metabolism
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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
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Physiology of growth
• GH/IGF-1
• T3,T4
• glucocorticoids
• estrogens
• androgens
• insulin
• genetic factors
• Nutrition: proteins, vitamins, minerals, calories
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Growth periods
• Rat continue growth
• Human
– 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
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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
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Neurohypophysis• Hormones: only storage in hypophysis
– ADH (vasopressin)
– Oxytocin
• Hormone production: hypothalamus Supraoptic, Paraventricular nuclei
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ADHADH•Antidiuretic hormone (vasopressin)
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
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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
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Increase Inhibit
Increased plasma osmolarity
Decreased blood volume
Decreased blood pressure
Angiotensin II
Nausea
Hypoxia
Pain
Exercise
Regulation of ADH secretion
Decreased plasma osmolarity
Increased blood volume
Increased blood pressure
Alcohol
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Hormonal control
of osmolarity by
ADH
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Oxytocin (9 AA)• Action mechanism
Metabotropic receptor => IP3/DAG => IC calcium level ↑
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Effects• Milk ejaculation reflex (myoephithel cell contraction)
• Uterus contraction (enhanced by estrogen, inhibited byprogesterone)
• Luteolysis
• Increased time of ejaculation (contraction of vas deferens)
• Establishment of maternal behavior
• Learning, pain, memory
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
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Pineal gland
– Atrophy in adult
• Hormone:
– melatonin (tryptophane
derivative)
• Metabolism: liver
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• 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
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)
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