Hypothalamus and adenohypophysis
Sensory
Neuroendocrine regulation
THALAMUS
- NON-SPECIFIC NUCLEI
- SPECIFIC SENSORY NUCLEI
- SPECIFIC NONSENSORY NUCLEI
- ASSOCIATION NUCLEI
HYPOTHALAMUS
- SYSTEM OF SEVERAL DOZENS OF NUCLEI
- PARAVENTRICULAR
- MEDIAL
- LATERAL REGION
HYPOPHYSIS
- PARS DISTALIS (STH, PRL, TSH, FSH, LH,ACTH)
- PARS TUBERALIS (FSH, LH)
- PARS INTERMEDIA (MSH)
Reticular activating substance
Limbic system Thalamus
ViscGral ■
Hormonal
Substrates'
Anterior
■ ACTHr GHr
TSH, Prl, LH, FSH
Posterior •OT& AVP
Metabolism
Water balance
Growth Ä development
Parturition & lactation
Reproduction
Lactation
Response to stress
Ventrolateral medulla (heart, stomach)
Amygdala (associative regions of neocortex,
olfactory bulb, hippocampal formation, subcortical structures including brain stem)
Hippocampus (associative regions of neocortex, thalamus, reticular formation nuclei, etc.)
Nucleus solitarius (viscerosensory information-heart, lungs, GIT, blood vessels -baro-/chemoreceptors)
Hypothalamus
Orbitofrontal cortex (sensory perception, reaction to _reward/punishment)_
Locus coeruleus (prefrontal cortex, N. paragigantocellularis -integration of external and autonomic stimuli - stress, panic)
Lamina terminalis (blood, blood composition)
Behavior
Body temperature regulation
Neuroendocrine regulation
Appetitive behavior (hunger, thirst, sexual behavior
Defensive reactions
Biorhythms and their regulation
Autonomic nervous system (modulation)
Circumventricular organs
Eminentia mediana Afferent sensoric organ Functional connection of hypothalamus and hypophysis Point of entry of some hormones from circulation (fenestration) - leptin CONVERSION - HUMORAL FACTORS -HYPOTHALAMIC REGULATION NEURONS
OVLT
Regulation of autonomous
processes
Febrile regulation
Blood osmolality
Regulation of secretion of GnRH
stimulated by estrogens
Area postrema Afference (n. vagus, n. glossopharyn-geus) R for GLP-1 and amylin Chemosensoric neurons with osmoR „detection" of toxins coordinated   regulation   of blood pressure (R for ATM, ADH, ANP)
Subfornical organ Body fluid homeostasis Blood pressure regulation (R for ANP and ATM Oxytocin secretion regulation
Subcommissural organ Mainly unknown function R for neuropeptides and neurotransmitters ? Production of somatostatin „catching" of monoamines from CSF
CC - corpus calosum OC - chiasma opticum ac - commisura anterior pc- commisura posterior AP - area postrema CP - choroid plexus ME - eminentia mediana NH - neurohypophysis OVLT - Organum vasculosum laminae terminalis PI - pineal gland/epiphysis SCO - subcommissural organ SFO - subfornical organ
Anatomical and functional connection of hypothalamus and hypophysis, neuroendocrine secretion
Magnicellular Neuron
Location: SON, PVH
(AVP, OXY)
Vasopressin and oxytocin
Kidney, Uterus, Mammary Gland
Parvicellular Hypophyseotropic Neuron
Location: PeVH, PVH (TRH, CRH, Somatostatin)
Arc
(GHRH, GnRH, Dopamine)
Hypothalamus
Releasing factors
Tropic hormones (ACTH, TSH, GH, LH, FSH, Prolactin)
Anterior Pituitary Gland
Hypothalamic Projection Neuron
Location: PVH
(AVP, OXY) LHA
(MCH, ORX) Arc
(POMC, AgRP)
Hypothalamic-releasing and hypolhalamic-inhtbiting hormones
Neuronal targets (e.g., sympathetic preganglionic neuron in spinal cord)
Neuronal Targets
Hormones released
Prolactin Growth hormone ■*
Thyrotropin
Luteinizing hormone Follicle-stimulating hormone
Corticotropin
Superior hypophysial artery
] [
Lactotroph
Mammo-somalolroph
Somatotroph Thyrotroph Gonadotroph
Corlicotroph
Hypothalamic hormones
Hypothalamic hormones are secreted in eminentia mediana region and enter portal circulation via fenestrations
Axons of oxytocin and ADH synthesizing neurons go through eminentia mediana region. Hormones are secreted in neurohypophysis
PIH (prolactin-inhibiting hormone) = dopamine
Environmental factors Neural stimuli I Hormonal stimuli
Synthesis and secretion I   S of hypothalamic
hormones_I
T
Vasopressin
Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2 (MW = 1084.38) Oxytocin
Cys-Tyr-lle-Gln-Asn-Cys-Pro-Leu-Gly-NH2 {MW = 1007.35)
Thyrotropin-Releasing Hormone
pGlu-His-Pro-NH2 (MW = 362.42) Gonadotropin-Releasing Hormone pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 (MW= 1182.39) Corticotropin-Releasing Hormone
Ser-Glu-Glu-Pro-Pro-lle-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu-lle-lle-NH2(MW = 4758.14)
Growth Hormone-Releasing Hormone
Tyr-Ala-Asp-Ala-lle-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-lle-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2 (MW = 5040.4)
Somatostatin
Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys (MW = 1638.12)
Vasoactive Intestinal Peptide
His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn-NH3 (MW = 3326.26)
Adenohypophysis
- ACTH	—	adrenocorticotropic hormone
- TSH	—	thyroid-stimulating hormone
- GH	—	growth (somatotropic) hormone
- PRL	—	prolactin
- LH	—	luteinizing hormone
- FSH	—	follicle-stimulating hormone
Adenohypophyseal cells	Represent ation	Hypothalamic hormone(s)	Adenohypophyseal hormones	Localization
Lactotropic	Up to 25 %	Dopamine	prolactin	whole AH
Cortikotropic	Ca 20 %	CRH	POMC-ACTH, ß-LPH, a-MSH, ß-end.	Anteromedial region
Thyreotropic	Ca 5 %	TRH	TSH	Anteromedial region
Gonadotropic	Up to 15 %	GnRH	LH/FSH	Posterolateral region
Somatotropic	Ca 40 %	GHRH/GHIH	GH	Posterolateral region
Thyroid hormone
Growth & differentiation Energy balance
Cortisol, aldosterone, & androgens
HsO & Na balance Inflammation & metabolism
LH & FSH
Insulin-like growth Factor
Growth & differentiation
HORMONE PRODUCTION UNDER DIRECT HYPOTHALAMIC CONTROL
Estrogen, progesterone, & testosterone
Reproductive function & behavior
Breast development Milk production
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Adenohypophyseal hormones
Anterior pituitary hormones	
Glycoproteins; TSH, FSH, LH i J	• Common a-subunit • Unique fi-subunit • Confers biological specificity _J
	
r i Proopiomelanocortin <POMC) V. J	-] • Post-translational cleavage • ACTH, ^-endorphin, a-, |J- and y- melanocyte stimulating hormones (MSH)
	
Growth hormone & prolactin j	* Prolactin * Growth hormone * Structural & genetic - Human placental lactogen |
	
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Suprachiasmatic nucleus   Circulating hormones
Axis GHRH/GHIH-GH-IGF-1
GHRH, growth hormone-releasing hormone
Characteristics
- Two types present in hypothalamus
- GHRH receptor (cAMP)
- R - homology with R secretin, GLP-1, glucagon, calcitonin, PTH, PTHrP
Hypothalamo-hypophyseal axis
- Fast GH secretion
- + estrogens, glucocorticoids and starvation
- - Somatostatin, age and obesity
Clinical significance
- Nowadays without clinical significance GHRP
Regulation of secretion - stimulation
- Ghrelin
- Leptin
- Galanin
- GABA
- a2-adrenergic and dopaminergic input
inhibition
- CRH
- (32-adrenergic input
Somatostatin (GHIH, growth hormone-inhibiting hormone )
Characteristics
-   Neurotransmitter - neuromodulator
Hypothalamo-hypophyseal axis
- GH secretion regulation
- TSH inhibition
- PRL and ACTH secretion inhibition Clinical significance
- Somatostatin analogues (octreotide, lanreotide, vapreotide, seglitide, pasireotide)
- Therapy of acromegaly, TSH producing or neuroendocrine tumors
- ! Negative GIT side effects
- Imaging methods (mln-somatostatin)
- Potential use in tumor treatment
Main effects of somatostatin
Inhibition of hormone secretion	GIT inhibition	Other
Adenohypophysis-TSH, GH, ACTH, PRL	Stomach and duodenal secretion including HCI	Inhibition of activated immune cells
GIT - gastrin, secretin, motilin, GLP-1, GIP, VIP	Stomach emptying	Inhibition of tumor growth (proliferation)
Endocrine pancreas - insulin, glucagon, (somatostatin)	Pancreatic enzymes and bicarbonates secretion	
Kidneys - renin	Bile secretion	
	Decrease of GIT blood flow	
	Stimulation of intestinal water and electrolytes absorption	
Growth hormone (GH)
Characteristics
-hGH genome - 5 products including human chorionic
somatomammotropin
-hGH-N - somatotrophs - 20/22 kDA
-hGH-V - placenta - feedback regulation
-Circulating GH:
- 20 (25 %) and 22 kDA (75 %) monomers
- Acetylated 22 kDA form
- Deaminated forms
Regulation of secretion
-GHRH, somatostatin, ghrelin, IGF-1, thyroid hormones, glucocorticoids -Relatively complicated system of regulation based on:
- Neuropeptides
- Neurotransmitters
- Endogenic opioids
Sleep Hypoglycemia Stress
Aging i (-) Disease Glucose
Chondrocytes t AA uptake f Protein synthesis Necessary for linear growth
Adipose GH excess Anti-insulin action
:, t Protein synthesi
Growth hormone (GH) - regulation of secretion
GHRH (continual), somatostatin (pulsatile secretion) Desensitization of R for GHRH IGF-1 - somatostatin
- Ghrelin
- GHS receptors - stimulation of GHRH secretion
- Synthesis - stomach and CNS, regulation of food intake
Diurnal rhythm with maximum during sleep (first episode of slow-wave sleep) Very low basal secretion, decrease with age (peak in puberty, then decrease)
Interval	Young Adult	Fasting	Obesity	Middle Age
24-h secretion (ug/24h)	540 ±44	2171 ± 333	77 ±20	196 ± 65
Secretory bursts (number in 24 h}	12 ± 1	32±2	3 ±0.5	10±1
GH burst (ug)	45 ±4	64 ±9	24 ±5	10±6
GH-IGF axis
Stimulation
Deep sleep u-Adrenergic Fasting Acetylcholine Sex steroids Stress Amino acids Hypogfycemia Ghrelin
IGF-1
Inhibition
Undernutrition Acute illness Chronic illness GH receptor
deficiency GHR antibodies IGF-1 receptor
deficiency
Suppression
Obesity P-Adrenergic Glucocorticoids FFA Glucose Hypothyroidism IGF-1
Catabotism
(auto/paracilne)
Stimulation of GH secretion
Physiological factors	Hormones and neurotransmitters	Pathological factors
Exercise	Arginin, lysin	Acromegaly
Stress (various causes)	Neuropeptides (ghrelin, GHRH, galanin, opioids - li receptors, melatonin)	TRH, GnRH
Sleep	Neurotransmitters (agonists a2-AR, antagonists ß-AR, Ml agonists, 5-HTD1 agonists, HI agonists)	Glu, Arg
Decrease in postprandial glycemia	GABA	IL-1, 2, 6
Starvation	Dopamine (D2R)	Protein depletion
Insulin-induced hypoglycemia	Estrogens	Starvation, anorexia nervosa
	Testosterone	Kidney failure
	Glucocorticoids (acute, not chronic)	Liver cirrhosis
		DM 1st type
nhibition of GH secretion
Physiological factors	Hormones and neurotransmitters	Pathological factors
Postprandial hyperglycemia, glucose infusion	Somatostatin	Acromegaly
Increased FAA in plasma	Calcitonin	L-DOPA
Increased GH concentration in plasma	Neuropeptide Y	D2R agonists
Increased IGF-1 concentration in plasma	CRH	Phentolamin
REM sleep	Neurotransmitters (al,2-AR antagonists, ß-AR agonists, HI antagonists, serotonin receptor antagonists, nicotine cholinergic receptor agonists)	Galanin
Aging	Glucocorticoids (chronic)	Obesity
		Hypothyroidismus
		Hyperthyroidismus
Growth hormone (GH) - regulation of secretion
Control day Fasting day
GH and interaction with other hormonal axes
ACTH - Glucocorticoids
Acute (+) - effect after ca 3 hours Chronic (-)
TRH - TSH - thyroid hormones
- Necessary for GH secretion
- Hypothyroidismus (-)
GnRH - FSH a LH - sex hormones
- Testosterone (+) Estrogens (+) - only p.o. - decreased inhibition of IGF-1 + feedback
aromatization of androgens affects GH synthesis and secretion (paracrine effect of estrogens in CNS)
TRANSPORT
-GHBPs
-20 kDA with low affinity -60 kDa with high affinity -Obesity (+) -Pregnancy(+) -p.o. estrogens (+) -Malnutrition (-) -Cirrhosis (-) -Hypothyroidism (-) -Androgens (-) -Glucocorticoids (-)
GH and its effects
METABOLIC
-Energetic metabolism
-Together with insulin (metabolism of sugars, fats, proteins) -Lipolysis and FA oxidation(+) (hormone-sensitive lipase, + LDL) -Glucose - direct or indirect effect,
- (+) uptake of Glu
- (-) Glu oxidation
- (+) gluconeogenesis -Proteins
- (+) anabolism, (-) urea
- (+) AA transport
- (+) incorporation of AA to proteins
- (-) protein oxidation
GROWTH
-Mediated bv IGF-1 (auto-/oaracrine)
Pituitary
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IGF-1 IGFBP-3 ALS
Liver
150 kd <Oj| ^ (
Endocrine ■* IGF-1
K3FBP-3 fragment
X
Intravascular
Growth plate
íGF-1 Paracrine autocrine
Hormonal control
b GH
1 £
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:-
GH T3
GH - clinical aspects
GH deficiency - gained or congenital - often tumors or inflammation
- nonspecific symptoms (i.e. loss of energy, social isolation, loss of focus)
- myocardium changes (left ventricle)
GHR - mutation
Significance of markers (IGF-1, IGFBP3)
Substitution therapy - wide array of side-effects, contraindication - cancer
Experimental indications:
- catabolic states (i.e. extensive burns)
- osteoporosis -HIV/AIDS
- sport medicine -aging
Axis PIH-prolact
PIH, prolactin-inhibiting hormone
Characteristics - dopamine
Hypothalamo-hypophyseal axis
Inhibition of PRL (D2R) secretion - lactotropic cells ! Lactotrophs with continual high PRL production Paracrine and autocrine regulation of PRL secretion
Other functions and places of synthesis
- Blood vessels - vasodilatation (physiological concentrations) Kidneys - sodium secretion Endocrine pancreas - decrease in insulin secretion GIT - lower motility
Effect of dompamine on immune system Clinical significance
- Effect of medication on dopamine and PRL secretion
- Neurodegenerative diseases (Parkinson)
- Antipsychotics (antag.)
PROLACTIN-RELEASING FACTORS (PRF)
- TRH, oxytocin, VIP
- under specific conditions ADH, ATM, NPY, galanin, substance P, GRP, neurotensin
- prolactin-releasing peptide (PrRP) -stress, satiety (other parts of CNS)
- Important feedback mechanism (short loop) of PRL secretion regulation
- Circadian rhythm (maximum in the morning)
- Nipple stimulation (1-3 min, peak 10-20 min)
Prolactin - PRL
Characteristics
- Lactotropic cells (only PRL)
- Mammosomatotropic cells (PRL and GH)
- Hyperplasia - pregnancy and lactation
- Expression regulated by estrogens, dopamine, TRH, thyroid hormones
- PRLR - mammary gl., adenohypophysis, adrenal gl., liver, prostate, ovaries, testicles, small intestine, lungs, myocardium, SNS, lymphocytes
Regulation of secretion
- pulsatile secretion - 4 - 14 pulses/day
- Highest levels during sleep (REM, nonREM)
- Lowest between 10:00 and 12:00
- Lower secretion with aging
- TIDA cells - dopamine Paracrine - endothelin-1, TGF-(3l, calcitonin, histamine (-)
- FGF, EGF (+)
- TRH, estrogens, VIP, serotonin, GHRH in higher concentrations (+)
- Cholecystokinin - ?
1 DA release.
Hypothalamus
Sucking
Breast differentiation
Duct proliferation & branching
Glandular tissue development
Milk protein & lactogenic enzyme synthesis
Prolactin - functions
Production of breast milk during pregnancy and lactation = function necessary for survival
Other functions - metabolic, melatonin synthesis, maternal behavior
Development of mammary gland and lactation
- Puberty - development of mammary gland due to GH and IGF-1
- Effect of estrogens and progesterone
- At age 8-13
- During pregnancy proliferation of alveoli and production of breast milk proteins and colostrum
- During third trimester - colostrum production (PRL, estrogens, progesterone, GH, IGF-1, placental hormones)
- Lactation - increase of PRL after birth, without breastfeeding decrease after ca 7 days
- Accumulation of breast milk stops further production
- Role of OT
Reproductive function of PRL
Lactation = amenorrhea and secondary infertility Inhibition of GnRH secretion Role of kisspeptin neurons (PRLR) Possible role of metabolic factors
Immune function of PRL
Antiinflammatory effect ?
Clinical significance
- hyperprolactinemia   -  drugs   including some antihypertensives, chronic kidney failure
- Macroprolactinemia
- Galactorrhea - role of GH (acromegaly)
- PRL deficiency
AxisGnRH-LH/FSH-gonads
GnRH, Gonadotropin-Releasing Hormone, GnIH
Characteristics
- Specific origin of GnRH neurons outside of CNS
- Downregulation - malnutrition, lactation, seasonal effects, aging, continual GnRH
- Upregulation - effect of GnRH on gonadotrophs (menstrual cycle)
Hypothalamo-hypophyseal axis
- FSH, LH
- Importance of GnRH pulses frequency (glycosylation)
- Menstrual cycle, puberty and its onset
Clinical significance
- Continually distributed analogues of GnRH -treatment of estrogen/steroid-dependent tumors of reproductive system
- Premature puberty treatment (leuprorelin -agonist!)
40 ■
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	pulse/3 hr	
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■ 300 _ £
200 ~ x
100
20   16 10
5    10   15   20   25   30   35 40 Days
Regulation of secretion
- Inputs from various CNS regions (brain stem, limbic system)
- Inhibitory effect of sex-hormones with exception of estradiol (negative/positive feedback)
- Importance of kisspeptin for females
- Inhibitory effect of PRL
- Effect of circulating substrates (FA, Glu)
- Leptin (NPY, kisspeptin)
- Stress (various causes)
- Acute - disruption of MC without effect on fertility
- Chronic - disruption of fertility, lowering of circulating sex-hormones levels
Glycoproteins - FSH a LH
Characteristics
- Heterodimer, different expression of subunits, glycosylation
- Structurally close to hCG (placenta)
Regulation of secretion
- sex hormones, local factors - paracrine (activins, inhibins, follistatin)
- (+)-glutamate, noradrenaline, leptin
- (-)-GABA, opioids
- Key role of kisspeptins, neurokinin B and substance P in GnRH secretion - FSH/LH
- Estrogens, progesterone, androgens - direct effect on gonadotrophs, indirect through GnRH
- Estrogens (-) - inhibition of transcription (a)
- Kisspeptin - stimulation of LH/FSH, GnRH
- Estrogens (+) shift
- Progesterone (-) - influences pulsatile secretion of GnRH
- Testosterone, estradiol (-) - males, kisspeptin neurons and AR
GnRHR - Ca2+ mobilization Different half-life for circulating LH and FSH
Central nervous system
Hypothalamus
Anterior pituitary
Activin/ ^_ Follistatin *
Inhibin
LH/FSH
Gonad
- Stimulatory - Inhibitory
FSH and LH functions
FEMALES - FSH
LH
Growth and development of follicular cell (maturation) Biosynthesis of estradiol
Regulation of inhibin synthesis during follicular phase Upregulation of LH receptors (preovulatory follicles) Selection of dominant follicle Recruitment of follicles for next cycle
Stimulation of estrogen synthesis (theca) Oocyte maturation (preovulatory follicle) Rupture of ovulatory follicle, ovulation Conversion of follicle wall to corpus luteum
MALES LH
FSH
Intratesticular synthesis of testosterone (Leydig cells) Spermatogenesis (Sertoli cells)
Clinical significance
- Possible deficiency of gonadotropins
- Hypogonadotropic hypogonadism
- Kallmann syndrome
- Syndrome Prader-Willi
- Reproductive dysfunction
Activins and inhibins
Inhibins - dimeric peptides (a + 1 or two (3Aor(3B)
- inhibin A - dominant follicle, corpus luteum
- inhibin B - testes, luteal and early follicular phase of MC
- FSH inhibition
Activins
- dimeric peptides - dimers of (3 subunits
- FSH stimulation
- autocrine/paracrine factors
- other tissues - growth and differentiation
A :tivin A
Aclivin AB
	
	
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Inhibin A
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Key:
□ Inhibin i.-subunil
□ Inhibin fi-subunit
■ Aclivin type I receptor
■ Aclivin type II receptor
□ TGFBR3
□ Receptor-regulated Smad
■ Common Smad
□ ONA binding partner
■ Aclivin target gene (P) Phosphorylation
Hormones of hypothalamus secreted
by neurohypophysis
Oxytocin & Vasopressin are peptide hormones
Neurohypophysis
Synthesis - magnocellular neurons (SON, PVN)
Precursor protein (signal peptide, hormone, neurophysin 2, glycopeptide copeptin)
Posttranslational modification neurophysins + copeptin
-   ADH/OT +
Neurophysins - importance - ADH transport and secretion
Termination (neurohypophysis, eminentia mediana) Secretion - voltage-gated Ca2+ channels Circulation - free, elimination - kidneys, liver
Nucleus
Cell body
Neurosecretory vesicles are transported down the hypothafamo-hypophysial tract. Hormone processing occurs during this stage yielding hormone and neurophysins.
Pre-prohormone synthesis in ER followed by packaging into secretory granules in GA occurs in the cell body of magnocellular neurons.
AVP N H3-Cys-Tyr-P he-Gi n-Asp-Cys-Pro-u-Arg-G I y-N H2
Oxytocin NH2-Cys-Tyr-lie-Gin-Asp-Cys-Pro-L-Leu-Gly-WH2
Contents of neurosecretory vesicles are released from nerve terminals in the posterior pituitary. Exocylosis is triggered by Ca2* influx through vollage-gated channels opened during neuronal depolari2ation.
Mitochondria
Synaptic vesiel
Oxytocin
PVN & SON
Fear, pain, noise, fever
Stretch of cervix End öl pregnancy
Myoepithelial celt contraction & milk ejection
	Uterine
	contraction
Characteristics
- Mechanoreceptors/tactile receptors
endogenous opioids, NO, GABA (-) Prolactin, relaxin (-), Estrogens (+)
- Works together with prolactin and sex hormones
Functions
- Lactation (under 1 min)
- Childbirth
rhythmical contractions of smooth muscles (gap-junction, stimulation of prostaglandin synthesis -extracellular matrix) postpartum bleeding, uterus involution
- Ejaculation (males)
- Behavior
Other functions and places of synthesis
- CNS
- Stimulation of ACTH secretion through CRH
- Stimulation of ADH/induced vasoconstriction
- Stimulation of prolactin secretion Memory traces recollection inhibition Maternal behavior
Clinical significance
- Oxytocin analogues
Antidiuretic hormone (ADH, vasopresin, AVP)
Characteristics
- receptors (G protein)
- V1R - Vla (Gq/11) - liver, smooth muscles, CNS, adrenal glands -only ligand ADH
- V2R (GJ-kidneys
- V3R - Vlb (Gq/11) - corticotropic cells (CNS), kidneys, thymus, heart, lungs, pancreas, uterus
Function
- Water reabsorption (distal tubule, collecting tubule) -tubular system with different water permeability in different parts
- AQPl - proximal tubule, HL descending limb HK - 90 % of water reabsorption
- AQP2 - collecting tubule (only ADH; acute X chronic effect)
- AQP3, AQP4
- Vasoconstriction (hemorrhagic shock, sepsis)
Other functions and places of synthesis
- CNS - increased recollection of memory traces
- Periphery - stimulation production of factor VIII and von Willebrand factor
Principal cell distal tubule
Lumen collecting duct
ADH - regulation of secretion
Osmotic regulation Regulation volume-pressure Predominantly inhibitory effect of R on I maenocellular N
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0      +10    +20    +30 (Osmolality) 0      -10    -20    -30 (Pressure or volume) Percent change
ADH is the main hormone regulating water homeostasis and osmolality, RAAS is the main regulatory system of blood volume and pressure.
< 4
1 2 J?
K 0
10% blood loss
„ MABP
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Baroreceptor stretch and firing
270   230   290    300 310 Plasma osmotarity (mOsm/L)
T Plasma osmolarity
I
Shrinkage of osmoreceptors
9th and 10th cranial nerve afferents
í Sympathetic tone
Less sensitive than osmoreceptors 5-10% I blood volume
? AVP release
+
i Magnocellular neuron inhibition
t HĚ0 reabsorption T Blood pressure
ADH - clinical aspects
Diabetes insipidus (Dl)
- Primary polydipsia
- Decreased ADH synthesis/secretion (ADH gene) (neurogenic)
- Decreased kidney sensitivity (nephrogenic)
SIADH - Syndrome of Inappropriate Antidiuretic Hormone Secretion
- Increased ADH synthesis/secretion
- Absence of physiological ADH secretion stimuli
Absence of thirst after osmotic stimulation Ethanol lowers ADH secretion
Unregulated ADH secretion
Reset of osmostat
12n
Increased basal ADH secretion