diencephalon : thalamus + hypothalamus2 function of hypothalamus • autonomic (sy. parasy.) –...

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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

• 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.

Role of Hypothalamus

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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.

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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

– TSH (thyroid-stimulating hormone), glycoprotein

– FSH (follicle-stimulating hormone), glycoprotein

– LH (luteinizing hormone), glycoprotein

– Prolactin, protein,

– GH (growth hormone), protein

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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

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Hormone of pars intermedia

• MSH

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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

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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III. Regulation of hormone secretionIII. Regulation of hormone secretion

Hypothalamus

Adenohypohysis

TRH (tripeptide)

Portal circulation

TSH

T3 és T4

Permanent cold

Birth

Excess calory intake

Leptin, MSH

Low circadian

Rhytm

Max: early morning

Min: afternoon

Cortisol

High amount of Iodine

Inhibitors of synthesis

+

+

Permanent stressFasting (AgRP)

Warmth

Dopamin, somatostatin

Neural

Growth

factors

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:

– 80-150th 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

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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

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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 ↑)

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 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)

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• 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

Effects:

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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)

•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

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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 => 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

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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

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• 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

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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)