ENDOCRINOLOGY Lec. 5 Dr. Ali al-bayati - PowerPoint Presentation

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ENDOCRINOLOGY

Lec. 5

Dr. Ali al-bayati

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Hypothalamus

Anterior pituitary

Posterior pituitary

Neurosecretory

neurons

Systemic

arterial

inflow

Hypothalamic-hypophyseal

portal system

System

venousoutflow

Hypophysiotropic H.:

Anterior pituitary hormones:

1

2

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Present in the base of the skull in “sella turcica”.

Connected to the hypothalamus by infundibular stalk.

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Hormones of the anterior Pituitary gland

The anterior pituitary hormones;The anterior lobe (or adenohypophysis) secretes hormones that regulate a wide variety of bodily functions. There are five anterior pituitary cells that secrete seven hormones:

composed of two distinctive parts:

The anterior pituitary; (adenohypophysis)

is a classical gland composed predominantly of cells that secrete protein hormones.

The posterior pituitary (neurohypophysis) tropins (troposG = turning) or trophic (trophikosG = nursing) hormones

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Acidophils

Cells that contain the polypeptide hormones:Somatotropes which produce growth hormoneLactotropes which produce 

prolactinBasophils

Cells that contain the glycoprotein hormones:

Thyrotropes

 which produce thyroid stimulating hormoneGonadotropes which produce luteinizing hormone or follicle-stimulating hormoneCorticotropes which produce adrenocorticotrophic hormoneDue the high carbohydrate content of the hormones within acidophils, they also stain bright purple with PAS stains.Chromophobes

These are cells that have minimal or no hormonal content. Many of the chromophobes may be acidophils or basophils that have degranulated and thereby are depleted of hormone. Some chromophobes may also represent stem cells that have not yet differentiated into hormone-producing cells.

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Growth Hormone

known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotrophs of the anterior pituitary gland. It is a single polypeptide chain with 191 amino acids.

The metabolic effect of GH is partly mediated by

somatomedin

, also known as

insulin-like growth factor-1 (IGF-1). Plasma concentration of GH is less than 2 ng/mL during day time,with secretary peak appearing 3 hours after meals. Maximum levelof GH is seen during deep sleep.

For measurement of serum GH, the samples are collected during sleep and also during waking hours to assess the circadian rhythm.

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Actions of growth hormone

It causes growth of almost all tissues of the body that are capable of growing. It promotes increased sizes and No.of the cells, with development of greater numbers of cells and specific differentiation of certain types of cells such as bone growth cells and early muscle cells.

metabolic effects, including

increased rate of protein synthesis in most cells of the body;

increased mobilization of fatty acids from adipose tissue, increased free fatty acids in the blood, and increased use of fatty acids for energy;

decreased rate of glucose utilization throughout the body. Thus, in effect, growth hormone enhances body protein, decreases fat stores, and conserves carbohydrates.

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Insulin-like growth factor-1 (IGF-1) Somatomedin

growth hormone causes the liver to form several small proteins called somatomedins that have the potent

effect of increasing all aspects of bone growth.

Why???

Growth hormone

binds only weakly to the plasma proteins. Therefore, consumed rapidly, having a half-time in blood of less than 20 minutes. By contrast, IGF-1 attaches strongly to a carrier protein in the blood, As a result, with a half-time of about 20 hours. This slow release greatly prolongs the growth-promoting effects of growth hormone.

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Actions of growth hormoneGH enhances Stimulation of growth of bone, Cartilage and connective tissue. Before

Epiphyseal Closure-GH through somatomedin, stimulate proliferation of chondrocytes, appearance of osteoblast, Stimulation of DNA & RNA synthesis and collagen formation. Increase in the thickness of epiphyseal end plate.After epiphyseal closure bone length can no longer increase by GH but bone thickening can occur through periosteal growth.

Control of Growth Hormone SecretionRate of growth many

factors, including stress, exercise, nutrition, sleep and growth hormone itself. However, its primary controllers are two hypothalamic hormones and one hormone from the stomach:

Growth hormone-releasing hormone (GHRH)

It is a hypothalamic peptide that stimulates both the synthesis and secretion of growth hormone.Somatostatin (SS) is a peptide produced by several tissues in the body, including the hypothalamus. Somatostatin inhibits growth hormone release in response to GHRH and to other stimulatory factors such as low blood glucose concentration.Ghrelin is a peptide hormone secreted from the stomach. Ghrelin binds to receptors on somatotrophs and potently stimulates secretion of growth hormone.

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Control of Growth Hormone Secretion

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Abnormalities of GH

During childhood: Excess GH cause gigantism while deficiency causes short stature.During adults: Excess cause acromegaly while deficiency very rarely causes symptoms. Gigantism :-

Is caused by excess GH secretion in childhood before fusion of the epiphyseal plates. Heights of up to 7 feet (2.1 m) may be reached.

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Acromegaly:-

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Prolactin (PRL);

Prolactin is a single-chain protein hormone closely related to growth hormone. It is secreted by so-called Lactotrophs in the anterior pituitary.

Hormone structure is stabilized by three intermolecular disulfide bonds.

Prolactin shares a 40% sequence homology to GH. This homology suggests that these hormones arose from a common ancestral gene.

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different actions have been reported for prolactin in various species. Some of its major effects are:1. Mammary Gland Development, Milk Production and Reproduction2. Effects on Immune Function

The prolactin receptor is widely expressed by immune cells, and some types of lymphocytes synthesize and secrete prolactin. suggest that prolactin may act as an autocrine or paracrine modulator of immune activity.

Increased in PRL levels in:

After

stress of gynecological examination

Stress of blood collection, nipple manipulation.During sleep During pregnancy During lactation.Pathological increase in PRL in female is associated with:- Amenorrhea (cessation of menses)Galactorrhea (breast discharge)Female infertility.Increased in PRL in male has been associated with

Gynecomastia (breast enlargement in men)Impotence in men (decreased sperm production).

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Control of Prolactin SecretionInhibition;

hypothalamus suppresses prolactin secretion from the pituitary. Dopamine serves as the major prolactin inhibiting factor or brake on prolactin secretion.

Stimulation

prolactin secretion is positively regulated by several hormones

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Prolactin release factor (PRF):thyroid-releasing hormone, gonadotropin releasing hormone and vasoactive intestinal polypeptide. Estrogens

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Adrenocorticotropic Hormone (ACTH)

It is secreted as a large precursor molecule, known as pro-opiomelanocortin (POMC),(POMC

) is synthesized and proteolytically chopped into several fragments as depicted

below;

Lipotropin:

weak lipolytic effects, the precursor to beta-endorphin.Beta-endorphin and Met-enkephalin: Opioid peptides with pain-alleviation and euphoric effects.

Melanocyte-stimulating hormone (MSH):

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The active adrenocorticotropic hormone (ACTH) is a polypeptide with 39 amino acids

.ACTH is released from the pituitary in a pulsatile manner, with a definite diurnal rhythm, the secretion being highest in the early morning and minimum at midnight

Factors that increase ACTH secretion include stresses such as pain, cold exposure, acute hypoglycemia, trauma, depression, and surgery.

ACTH binds to specific receptors on the adrenal gland, then activates adenylate cyclase and so, cAMP level is raised. ACTH induces adrenocortical steroidogenesis through the

ACTH secreting tumors of pituitary will cause Cushing’s disease. Deficiency of ACTH secretion may occur as a part of panhypopituitarism

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Cosyntropin stimulation (Rapid ACTH) test: administration of ACTH, blood cortisol level will be raised. If there is adrenal insufficiency, adrenal gland cannot be stimulated by the administered ACTH and subnormal or low response of cortisol occurs

.Dexamethasone suppression test: Dexamethasone, suppresses ACTH hormone and cortisol production in normal subjects; but not in patients with Cushing’s syndrome.

Blood test

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Anterior pituitary glycoproteins hormones;

TSH, LH, and FSH are called glycoproteins because they contain complex carbohydrates known as glycosides.

composed of two glycopeptide chains, the alpha chain, is identical in all three hormones. the

beta chain, differs in structure for each hormone, thereby explaining the different actions of TSH, LH, and FSH.

Thyroid Stimulating

Hormone, thyrotropinis secreted from cells in the anterior pituitary called thyrotrophsstimulates synthesize and release thyroid hormones. It acts through cAMP by binding with a receptor on thyroid cell surface.

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FSH and LH are secreted under the effect of gonadotropin releasing hormone (GnRH).

Puberty does not set in until the pulsatile secretion of LHRH is started by hypothalamus.

The fundamental change during puberty is a reduction in hypothalamic inhibition of LHRH release.

Luteinizing Hormone

In

women,the ovaries respond to LH stimulation by secretion of testosterone, which is converted into estrogen by adjacent granulosa cells. Two weeks into a woman's cycle, a surge in luteinizing hormone causes the ovaries to release an egg during ovulation (ovulatory function)If fertilization occurs, luteinizing hormone will stimulate the corpus luteum, which produces progesterone to sustain the pregnancy.

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Thank you