Hypothalamus & Pituitary Gland
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 2
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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 4
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 5
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 6
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 7
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 8
Glycoprotein Hormones Thyroid-stimulating hormone (TSH), also called thyrotropin Follicle-stimulating hormone (FSH) Hormone Target Major actions in humans Thyroid gland Stimulates synthesis and secretion of thyroid hormones 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 luteum Testis Stimulates interstitial cells of Leydig to synthesize and secrete testosterone 9
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 Hormone Target Major actions in humans Growth hormone (GH), also called somatotropic hormone (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 10
Adrenocorticotropin Family 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 Hormone Target Major actions in humans Adrenocorticotropic hormone (ACTH), also known as adrenocorticotropin or corticotropin β-lipotropin Adrenal cortex Promotes synthesis and secretion of adrenal cortical hormones Adipose Physiological role not established Tissue 11
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 12
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 13
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 14
Physiology of the Posterior Pituitary Oxytocin and AVP are stored in and secreted by the posterior pituitary gland, but are synthesized by the hypothalamus 15
Regulation of Posterior Pituitary Function Regulation of oxytocin secretion showing a positive feedback arrangement. Increased blood osmolality or decreased blood volume are sensed in the brain or thorax, respectively, and increase vasopressin secretion. 16
Hypophysiotropic hormones Hormone Physiological actions of the pituitary 17
Pituitary & Hypothalamic Disorders Hypothalamic-pituitary lesions present with a variety of signs, including pituitary hormone: hypersecretion and hyposecretion, sellar enlargement, and visual loss 18
Pituitary & Hypothalamic Disorders In adults, the most common cause of hypothalamicpituitary 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) 20
Thyrotrophin Disorders Hyposecretion produces a clinical picture similar to primary thyroid deficiency Hypersecretion gives the symptoms of hyperthyroidism similar to Graves disease 21
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 22
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 23
Hyposecretion GHRH Disorders 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 24
Hyposecretion Vasopressin Disorders 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) 25
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 26
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 27
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 28