Download Endocrinology-general physiolofy of hormone, hormonal feed

Hypothalamus and its hormones,
hormones of the pituitary gland
Romana Šlamberová, M.D. Ph.D.
Department of Normal, Pathological and
Clinical Physiology
The hypothalamus
Hormonal (anterior portion) or nervous (posterior
portion) control of the pituitary gland
 Hormones – control secretion of hormones in the
anterior pituitary
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Releasing hormones (factors)
Inhibitory hormones (factors)
Hormones secreted and transported to anterior pituitary
through hypothalamic-hypophysial vessels to pituitary
sinuses
 Nerves – Magnocellular neurons in the supraoptic and
paraventricular nuclei of the hypothalamus – axoplasm
transport of hormones from the hypothalamus to the
posterior pituitary
Hypothalamic-hypophysial portal
system (1)
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Special neurons in the hypothalamus synthesize
and secrete the hypothalamic releasing and
inhibitory hormones that control secretion of anterior
pituitary
These neurons originate in various parts of the
hypothalamus and send their nerve fibers to the
median eminence and tuber cinerreum (extension
of hypothalamic tissue into the pituitary stalk)
Hormones are secreted to the tissue fluids,
absorbed into the hypothalamic-hypophysial
portal system and transported to the sinuses of the
anterior pituitary
Hypothalamic hormones controlling
anterior pituitary gland (1)
Major hypothalamic releasing hormones:
 Thyreotropin-releasing hormone (TRH) –
causes release of thyroid stimulating hormone
(TSH)
 Corticotropin-releasing hormone (CRH) –
causes release of adrenocorticotropin hormone
(ACTH)
 Growth hormone releasing hormone (GHRH)
– causes release of growth hormone
 Gonadotropin releasing hormone (GnRH) –
causes release of the 2 gonadotropic hormones
(luteinizing and follicle-stimulating hormone)
Hypothalamic hormones controlling
anterior pituitary gland (2)
Major hypothalamic inhibitory hormones:
 Growth hormone inhibitory hormone
(GHIH) = SOMATOSTATIN – inhibits
release of growth hormone
 Prolactin inhibitory hormone (PIH) –
inhibits prolactin secretion
The pituitary gland

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1 cm in diameter
0.5 – 1 g in weight
In sella turcica (bony cavity
at the base of the brain
Connected to the
hypothalamus via pituitary
stalk
Parts:

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Adenohypophysis – anterior
Neurohypophysis - posterior
Pars intermedia (almost
absent in humans)
Hormones of the adenohypophysis
(1)
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Human growth hormone (hGH) – affects protein
formation, cell multiplication, cell differentiation
Adrenocorticotropin (ACTH) – controls secretion of
some of the adrenocortical hormones (affects metabolism
of glucose, proteins and fats)
Thyroid-stimulating hormone (STH) – controls secretion
of thyroxine and triodothyronine by the thyroid gland
(controls rates of most intercellular chemical reactions of
the entire body)
Prolactin – promotes mammary gland development and
milk production
Follicle-stimulating hormone (FSH) and Luteinizing
hormone – control growth of the ovaries and testes and
their hormonal and reproductive functions
Hormones of the adenohypophysis
(2)
Other hormones of
adenohypohysis
 β-Lipotropin (β-LPH)
– function unknown
 γ-Melanocytestimulating hormone
(γ-MSH) – stimulates
melanin synthesis in
melanocytes
Cell types in the anterior
pituitary
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
Chromophobes – mostly inactive cells with only few
secretory granules
Chromophils – active secretory cells


Cell type
Somatotrope
Lactotrope
Corticotrope
Thyrotrope
Gonadotrope
Acidophils (stained with acidic dyes)
Basophils (stained with basic dyes)
Hormones
secreted
% of total
secretory cells
Stain affinity
Diameter of
secretory
granules (nm)
hGH
50
Acidophilic
300-400
Prolactin
10-30
Acidophilic
200
ACTH
10
Basophilic
400-550
TSH
5
Basophilic
120-200
FSH, LH
20
Basophilic
250-400
Hormones of Intermediate lobe

Melanocytes stimulating hormones (MSH) –
types α, β, γ.
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In humans – stimulate melanin synthesis in
melanocytes
In fish, amphibians and reptiles – expand
melanophores
γ- Lipotropin (γLPH) and Corticotropin-like
intermetiate lobe peptide (CLIP)


From prehormone POMC (pro-opiomelanocortin)
Function unknown
Hormones of the neurohypophysis
Magnocellular neurons (long neurons) located
in the supraoptic and paraventricular nuclei of
the hypothalamus – axoplasm transport of
hormones from the hypothalamus to the posterior
pituitary
 Hormones: Polypeptides with 9 amino acids
ADH (vasopressin): Cys-Tyr-Phe-Gln-Asn-CysPro-Arg-GlyNH2
Oxytocin: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-LeuGlyNH2
 Similar structure, similar action

Cell types in the posterior
pituitary
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Pituicytes = glial-like
cells
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no hormone secretion
supporting structure for
terminal nerve fibers and
endings
Axons of secretory
neurons located in
the supraoptic and
paraventricular nuclei
of the hypothalamus
ADH (vasopressin)


Formed primarily in the supraoptic nuclei
Regulates water excretion by the kidneys

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Increases the permeability of collecting tubules and
ducts to water - water reabsorption – concentrated
urine
Osmotic regulation – osmoreceptors in the
hypothalamus or somewhere near
Causes vasoconstriction

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Constrict arterioles throughout the entire body
Blood volume (activated when decreased blood
volume)
– stretch (volumoreceptors) in right atrium of the
heart
- baroreceptors in carotid, aortic and pulmonary
regions
Oxytocin

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Formed primarily in the paraventricular nuclei
Causes contraction of the pregnant uterus
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Oxytocin plasma levels increase in the last stage of labor
Cervix stimulation during labor elicit nervous signals to
hypothalamus and the secretion of oxytocin increases
Aids the milk ejection by the breasts
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The suckling stimuli cause signals to be transmitted
through sensory nerves to the oxytocin neurons in the PV
and SO nuclei of the hypothalamus.
Oxytocin causes contraction of myoepithelial cells around
the alveoli.
In less than a minute after suckling started the milk
begins to flow.
Growth hormone (somatotropic
hormone, somatotropin)
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Chemical structure: small protein (191 amino
acids)
Function: hGH enhances body protein, uses
up the fat stores and conserves
carbohydrates
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Increases rate of protein synthesis in most cells of
the body
Increases mobilization of fatty acids in the blood and
increases use of the fatty acids for energy
Decreases rate of glucose utilization throughout the
body
hGH - Function (1)
Increase in protein deposition

Enhancement of amino acid transport through
the cell membrane to the interior of the cells
(more AAs available for protein synthesis)

Enhancement of RNA translation to cause
protein synthesis by the ribosomes (even when
the AAs concentration are not increased)


Increase in nuclear translation of DNA to form
RNA
Decrease in catabolism of protein and amino
acids
hGH - Function (2)
Increase in fat utilization for energy

Causing release of fatty acids from adipose
tissue (increase in fatty acid concentration in the body
fluid)

Enhancement of conversion of fatty acids to
acetyl coenzyme A (subsequent utilization of it for
energy)

Ketogenic effect of hGH – ketosis may occur
when the amount of hGH is too high and
causes great mobilization of fatty acids from
adipose tissue that requires large amount of
acetoacetic acid formed by the liver (may cause
fatty liver)
hGH - Function (3)
Decrease in carbohydrate utilization

Decrease in glucose uptake in tissues (skeletal muscle and
fat)
Increase in glucose production by the liver
 Increase in insulin secretion
hGH has DIABETOGENIC EFFECT
= growth hormone-induced “insulin resistance” attenuates
insulin’s actions, such as:
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To stimulate uptake and utilization of glucose in skeletal muscle
and fat
To inhibit glucose output by the liver
This leads to increase of glucose concentration in the blood
and compensatory increase of insulin.
Excess in hGH may cause metabolic disturbance similar to
those found in patients with DM II.
hGH stimulates cartilage and bone
growth
Cartilages and bones are the main tissues of hGH
action
 Increased deposition of protein by the chondrocytic and
osteogenic cells that cause bone growth
 Increased rate if reproduction of these cells
 Specific effect of converting chondrocytes into
osteogenic cells (causing specific deposition of new bone)
 2 principle mechanisms of bone growth:
 Growth in length (during development before closing the
epiphysal slit)

Growth in width (also after adolescence) – hGH stimulates
osteoblasts
Somatomedins
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Secreted by the liver and other tissue based of the hGH
stimulation
Similar effect as insulin = IGF (insulin-like growth
factors)
Function: support the action of hGH (unclear is if the
hGH may act without somatomedines or not)
Types:
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Somatomedin C = IGF I
IGF II
Regulation of hGH secretion
(1) - stimulation
hGH is secreted in pulsation – increasing and
decreasing
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Factors stimulating secretion:
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Starvation (especially with protein deficiency)
Hypoglycemia
low fatty acids in the blood
Exercise
Excitement
Trauma
The first 2 hrs of deep sleep (non-REM)
Hormones:
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GHRF = Growth hormone releasing factor
Estrogens and androgens
Regulation of hGH secretion
(2) - inhibition
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Factors inhibiting secretion:
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Hyperglycemia
High fatty acids in the blood
Aging
Obesity
REM sleep
Hormones:
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GHIH = Growth hormone inhibitory hormone
(Somatostatin)
Exogenous growth hormones
Somatomedins (IGF)
Abnormalities of hGH secretion
(1) - hypofunction
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Panhypopituitarism = decrease of secretion of all
anterior pituitary hormones
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Dwarfism
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Congenital
Induced by tumor that destroys the gland
Decrease of all or more than 1 hormone of anterior pituitary (the
person does not reach sexual maturation = missing gonadal
hormones)
Decrease just in hGH – only smaller person, but can maturate
Missing somatomedins
Panhypopituitarism in the adulthood
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Due to: tumor or trombosis of the pituitary blood vessels
Results in: hypothyroidism, decrease in glucocorticoids,
suppression of gonadotropic hormones
Abnormalities of hGH secretion
(2) - hyperfunction
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Gigantism – increased growing (randomly) =
giants
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Due to: increased activity of somatotropes or tumor
during development
Giants have hyperglycemia (DM)
Acromegaly – increased growing of acral parts
of the body
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Due to: increased activity of somatotropes or tumor
after puberty (after closure the epiphysal slits)
Bones grow only to thickness ( enlargement of hands
and feet, membranous bones such as cranium,
nose, supraorbital ridges, chin etc.