hypothalamus & pituitary...

Hypothalamus & Pituitary Gland

Dr. M. Alzaharna (2014)

Hypothalamus and Pituitary Gland

• The hypothalamus and pituitary gland form a unit that exerts control over the function of several endocrine glands (thyroid, adrenals, and gonads), as well as a wide range of physiologic activities

• This unit constitutes an example of neuroendocrinology—brain-endocrine interactions

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Dr. M. Alzaharna (2014)3


Morphology

• The pituitary gland (hypophysis) is located in a small depression in the sphenoid bone, the sella turcica, just beneath the hypothalamus

• It is connected to the hypothalamus by a thin stalk called the infundibulum

Sella turcica

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Histology of the Anterior Lobe

• Most of the cells in the anterior lobe (adenohypophysis) contain secretory granules, although some are only sparsely granulated

• Based on their characteristic staining with standard histochemical dyes and immunofluorescent stains, it is possible to identify the cells that secrete each of the pituitary hormones

• It once was thought that there was a unique cell type for each of the pituitary hormones, but it is now recognized that some cells may produce more than one hormone

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Histology of the Posterior Lobe

• The posterior lobe (neurohypophysis) consists of two major portions:

– the infundibulum, or stalk,

– and the infundibular process, or neural lobe

• The posterior lobe is richly endowed with fibers

• The cell bodies from which these fibers arise are located in the hypothalamus

• Secretory material synthesized in cell bodies in the hypothalamus is transported down the axons and stored in in the posterior lobe

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Physiology of the Anterior Pituitary Gland

• There are six anterior pituitary hormones whose physiological importance is clearly established

• They include the hormones that govern the function of the:

– thyroid and adrenal glands,

– the gonads,

– the mammary glands,

– and bodily growth

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Hormones of the Anterior Pituitary Gland

• All the anterior pituitary hormones are proteins or glycoproteins

• They are divided into 3 categories according to structure similarity:

– Glycoprotein Hormones

– Growth hormone and prolactin

– Adrenocorticotropin family

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Glycoprotein Hormones

Hormone Target Major actions in humans

Thyroid-stimulating hormone (TSH), also called thyrotropin

Thyroid gland • Stimulates synthesis and secretion of thyroid hormones

Follicle-stimulating hormone (FSH)

Ovary • Stimulates growth of follicles and estrogen secretion

Testis • Acts on Sertoli cells to promote maturation of sperm

Luteinizing hormone (LH) Ovary • Stimulates ovulation of ripe follicle • and formation of corpus luteum; • stimulates estrogen and progesterone

synthesis by corpus luteumTestis • Stimulates interstitial cells of Leydig to

synthesize and secrete testosterone9


Growth Hormone and Prolactin

• Somatotropes (GH producing cells) are by far the most abundant anterior pituitary cells, and account for at least half the cells

• Structurally, prolactin (PRL) is closely related to GH


Growth hormone (GH), also called somatotropichormone (STH)

Most tissues Promotes growth in stature and mass;

stimulates production of insulin-like growth factor (IGF-I);

stimulates protein synthesis; usually inhibits glucose utilization

and promotes fat utilization

Prolactin Mammary glands • Promotes milk secretion and mammary growth

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Adrenocorticotropin Family


Adrenocorticotropic

hormone (ACTH), also

known as adreno-

corticotropin or corticotropin

Adrenal cortex • Promotes synthesis and secretion of

adrenal cortical hormones

β-Lipotropin Adipose

Tissue

• Physiological role not established

• The ACTH related peptides constitute a family because:• they contain regions of homologous amino acid sequences,

which may have arisen through exon duplication, • and because they all are encoded in the same gene

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Regulation of Anterior Pituitary Function

• Secretion of the anterior pituitary hormones is regulated by:

– the central nervous system • provides the primary drive for secretion

– and hormones produced in peripheral target glands• and peripheral input plays a secondary, though vital, role in

modulating secretory rates

• Secretion of all the anterior pituitary hormones except PRL declines severely in the absence of stimulation from the hypothalamus as can be produced

• when the pituitary gland is removed surgically from its natural location and reimplanted at a site remote from the hypothalamus

– PRL secretion is normally under tonic inhibitory control by the hypothalamus

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Feedback Control of Anterior Pituitary Function

• Environmental factors may increase or decrease pituitary activity by increasing or decreasing hormone secretions from hypothalamus

• Pituitary secretions increase the secretion of target gland hormones, which may inhibit further secretion by acting at either the hypothalamus or the pituitary

• Pituitary hormones may also inhibit their own secretion by a short feedback loop

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Physiology of the Posterior Pituitary

• The posterior pituitary gland secretes two hormones which are:

– oxytocin ,

• increase uterine contractions during parturition

• Contraction of mammary glands to secret milk

– and vasopressin or arginine vasopressin (AVP) (or Antidiuretic Hormone ‘ADH’)

• contract vascular smooth muscle and thus raise blood pressure

• promote reabsorption of water by renal tubules

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Physiology of the Posterior Pituitary

• Oxytocin and AVP are stored in and secreted by the posterior pituitary gland, but are synthesized by the hypothalamus

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Regulation of Posterior Pituitary Function

Increased blood osmolality or decreased blood volume are sensed in the brain or thorax, respectively, and increase vasopressin secretion.

Regulation of oxytocin secretion showing a positive feedback arrangement.

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Hypophysiotropic hormones

HormonePhysiological actions of

the pituitary

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Pituitary & Hypothalamic Disorders

• Hypothalamic-pituitary lesions present with a variety of signs, including pituitary hormone:

– hypersecretion and hyposecretion,

– sellar enlargement,

– and visual loss

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Pituitary & Hypothalamic Disorders

• In adults, the most common cause of hypothalamic-pituitary dysfunction is a pituitary adenoma, of which the great majority are hypersecreting

• Thus, the earliest symptoms of such tumors are due to endocrinologic abnormalities and include:

– Early manifestation• Hypogonadism, the most frequent

– diminished functional activity of the gonads

– Late manifestation in patients with larger tumors or suprasellar extension• sellar enlargement

• headache

• and visual loss, 19


Gonadotrophins Disorders

• Hyposecretion

– leads to amenorrhoea,

– sterility

– and loss of sexual potency.

– In the young, the sex organs and secondary sexual characteristics fail to develop (delayed puberty)

• Hypersecretion

– extremely rare,

– in children it could lead to sexual precocity (excessive premature development)

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Thyrotrophin Disorders

• Hyposecretion

– produces a clinical picture similar to primary thyroid deficiency

• Hypersecretion

– gives the symptoms of hyperthyroidism similar to Graves’ disease

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Corticotrophin Disorders

• Hyposecretion

– rare

– causes failure of cortisol secretion,

– a general lack of health and well being,

– a reduced response to stress and skin depigmentation

• Hypersecretion

– due to a pituitary microadenoma,

– will result in Cushing’s syndrome

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Prolactin Disorders

• Hyposecretion– leads to failure of lactation in women

• Hypersecretion– may result from a pituitary tumour

– principal symptoms are infertility and menstrual complaints

– in men, decreased libido,

– inadequate sperm production and impotence, whereas in women, there may be a complete lack of menstruation

– inappropriate (non-pregnant) milk production

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GHRH Disorders

• Hyposecretion

– caused by hypothalamic or pituitary dysfunction

– In childhood this leads to impairment of growth (dwarfism)

• Hypersecretion

– This usually results from a benign pituitary tumour

– In young patients, this leads to gigantism

– In adults, leads to acromegaly

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Vasopressin Disorders

• Hyposecretion

– caused by damage or dysfunction of the hypothalamus,

– can lead to diabetes insipidus,

• excessively large amounts of dilute urine (10–15 liters/day) are produced by the kidneys

• Hypersecretion

– rare condition of inappropriate AVP production is known as syndrome of inappropriate ADH (SIADH)

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Hypopituitarism

• Hypopituitarism is manifested by diminished or absent secretion of one or more pituitary hormones

• Hypopituitarism is either:

– a primary event

• caused by destruction of the anterior pituitary gland

– or a secondary phenomenon

• resulting from deficiency of hypothalamic stimulatory factors normally acting on the pituitary

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Assessment of Target Gland Function

• If endocrine hypofunction is suspected, pituitary hormone deficiencies must be distinguished from primary failure of the thyroid, adrenals, or gonads

• Baseline laboratory studies should include: – thyroid function tests (free T4)

– and determination of serum testosterone levels

• Testosterone is a sensitive indicator of hypopituitarism in women as well as in men

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• In primary target gland hypofunction, such as autoimmune polyglandular syndromes types 1 and 2 (APS 1 and 2), TSH, LH, FSH, or ACTH will be elevated

• Low or normal values for these pituitary hormones suggest hypothalamic-pituitary dysfunction

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