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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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