Hypothalamus and its hormones, Hypothalamus and its hormones, hormones of the pituitary glandhormones of the pituitary gland

Romana Šlamberová, M.D. Ph.D.Romana Šlamberová, M.D. Ph.D.

Department of Normal, Pathological and Department of Normal, Pathological and Clinical PhysiologyClinical Physiology

The hThe hypothalamusypothalamus

Hormonal (anterior portion) or nervous (posterior portion) control of the pituitary gland

Hormones – control secretion of hormones in the anterior pituitary 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

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-hypophysial portal Hypothalamic-hypophysial portal system (1)system (1)

Hypothalamic hormones controlling Hypothalamic hormones controlling anterior pituitary gland (1)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)

Major hypothalamic inhibitory hormones: Growth hormone inhibitory hormone

(GHIH) = SOMATOSTATIN – inhibits release of growth hormone

Prolactin inhibitory hormone (PIH) – inhibits prolactin secretion

Hypothalamic hormones controlling Hypothalamic hormones controlling anterior pituitary gland (2)anterior pituitary gland (2)

The pituitary glandThe pituitary gland

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: Adenohypophysis – anterior Neurohypophysis - posterior Pars intermedia (almost

absent in humans)

Hormones of the adenohypophysisHormones of the adenohypophysis(1)(1)

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 adenohypophysisHormones of the adenohypophysis(2)(2)

Other hormones of adenohypohysis

β-Lipotropin (β-LPH) – function unknown

γ-Melanocyte-stimulating hormone (γ-MSH) – stimulates melanin synthesis in melanocytes

Cell types in the anterior Cell types in the anterior pituitarypituitary

Chromophobes – mostly inactive cells with only few secretory granules

Chromophils – active secretory cells Acidophils (stained with acidic dyes) Basophils (stained with basic dyes)

Cell type Hormones secreted

% of total secretory cells

Stain affinity Diameter of secretory

granules (nm)

Somatotrope hGH 50 Acidophilic 300-400

Lactotrope Prolactin 10-30 Acidophilic 200

Corticotrope ACTH 10 Basophilic 400-550

Thyrotrope TSH 5 Basophilic 120-200

Gonadotrope FSH, LH 20 Basophilic 250-400

Hormones of Intermediate lobeHormones of Intermediate lobe

Melanocytes stimulating hormones (MSH) – types α, β, γ. 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 neurohypophysisHormones 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-Cys-Pro-Arg-GlyNH2

Oxytocin: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2

Similar structure, similar action

Cell types in the posterior Cell types in the posterior pituitarypituitary

Pituicytes = glial-like cells 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

Formed primarily in the supraoptic nuclei Regulates water excretion by the kidneys

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 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

ADH (vasopressin)ADH (vasopressin)

OxytocinOxytocin

Formed primarily in the paraventricular nuclei Causes contraction of the pregnant uterus

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

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 Growth hormone (somatotropic hormone, somatotropin)hormone, somatotropin)

Chemical structure: small protein (191 amino acids)

Function: hGH enhances body protein, uses up the fat stores and conserves carbohydrates 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) hGH - Function (1) Increase in protein depositionIncrease 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) hGH - Function (2) Increase in fat utilization for energyIncrease 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)hGH - Function (3)Decrease in carbohydrate utilizationDecrease in carbohydrate utilization Decrease in glucose uptake in tissues (skeletal muscle and

fat) Increase in glucose production by the liver Increase in insulin secretionhGH has DIABETOGENIC EFFECT= growth hormone-induced “insulin resistance” attenuates

insulin’s actions, such as: 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 hGH stimulates cartilage and bone growthgrowth

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

SomatomedinsSomatomedins

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: Somatomedin C = IGF I IGF II

Regulation of hGH secretionRegulation of hGH secretion(1) - stimulation(1) - stimulation

hGH is secreted in pulsation – increasing and decreasing

Factors stimulating secretion: 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:

GHRF = Growth hormone releasing factor Estrogens and androgens

Factors inhibiting secretion: Hyperglycemia High fatty acids in the blood Aging Obesity

REM sleep Hormones:

GHIH = Growth hormone inhibitory hormone (Somatostatin)

Exogenous growth hormones Somatomedins (IGF)

Regulation of hGH secretionRegulation of hGH secretion(2) - inhibition(2) - inhibition

Abnormalities of hGH secretionAbnormalities of hGH secretion(1) - hypofunction(1) - hypofunction

Panhypopituitarism = decrease of secretion of all anterior pituitary hormones Congenital Induced by tumor that destroys the gland

Dwarfism 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 Due to: tumor or trombosis of the pituitary blood vessels Results in: hypothyroidism, decrease in glucocorticoids,

suppression of gonadotropic hormones

Abnormalities of hGH secretionAbnormalities of hGH secretion(2) - hyperfunction(2) - hyperfunction

Gigantism – increased growing (randomly) = giants Due to: increased activity of somatotropes or tumor

during development Giants have hyperglycemia (DM)

Acromegaly – increased growing of acral parts of the body 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.