The+Endocrine+System+I+-+Hypophysis+and+Pineal

=**Objectives**=


 * 1. Describe the histology of the pituitary gland; include the infundibular stalk, the four main parts, and its embryology.**

The Pituitary gland is small and oval shapped, attached by the infundibular stalk to the undersurface of the hypothalamus. It is covered by a dura capsule called the diaphragma sellae. The pituitary is divided into the pars distalis, pars tuberalis, pars intermedia, and pars nervosa.

The pars distalis is the largest anterior portion. The pars tuberalis arised from the pars distalis to wrap around the infundibular stalk. Cells in the pars tuberalis are arranged in short longitudinal cords closely associated with capillaries; the vasculature of the hypothalamo hypophyseal portal system cuts through the pars tuberalis on the way to the pars distalis. Gonadotrophs are mostly contained in pars tuberalis.

The pars intermedia is a thin cellular partition separating the pars distalis from the pars nervosa. This partition is composed of basophilic cells and is marked by an indentation called Rathke’s Cleft. In adult humans, the pars intermedia is composed of a thick layer of mostly chromophobic cells surrounding aggregates of colloid-filled follicles called Rathke’s Cysts that are filled with extracellular fluid despite being described as colloid-filled. Hormonal secretions of the basophils in the pars intermedia appear to have some effect in the production of melanocyte stimulating hormone, and low level ACTH synthesis.

The pars nervosa is a specialized neuroendocrine tissue attached to the medial eminence of the tuber cinereum of the hypothalamus. The anterior pituitary contains the pars distalis, pars tuberalis, and pars intermedia. The posterior lobe contains the pars nervosa, infundibulum, and median eminence.

Embryologically, the anterior pituitary is derived from an upgrowth of epithelial tissue from the roof of the oral ectoderm (Rathke’s pouch) and is also called the adenohypophysis. The posterior pituitary is derived from a downgrowth of neuroectoderm from the hypothalamus of the CNS and is also called the neurohypophysis.

The blood supply of the anterior lobe is derived from the superior hypohyseal arteries arising from the internal carotid arteries. These arteries anastomose in the upper portion of the pituitary stalk in the region of the median eminence where they give rise to the primary plexus. The primary plexus empties into a series of long portal veins which descend in the pituitary stalk to the anterior lobe where they branch to give rise to the secondary plexus. The secondary plexues drains by a series of inferior hypophyseal veins into the cavernous sinus. The primary plexus, portal veins, and secondary plexus are collectively knows as the hypothalamic hypophyseal portal system. Regulatory peptides from the hypothalamus are distributed to the anterior pituitary via the primary plexus; in response to these peptides, the cells of the anterior lobe release their hormones into the secondary plexus to be distributed via circulatory system to target organs.

Blood to the posterior pituitary is supplied by a pair of inferior hypophyseal arteries which arise from the internal carotids. These arteries anastomose in the parenchyma of the posterior lobe to form a dense capillary plexus emptying into the posterior hypophyseal veins.


 * 2. Identify chromophils and chromophobes in the pars distalis. Indicate which pituitary hormones are made by each, what is/are the function(s) of each hormone and what is the target organ, tissue or cell of each.**

The anterior pituitary’s pars distalis forms about 75% of the entire pituitary. The parenchyma of the pars distalis consists of dense cords of secretory epithelial cells, supported by reticular fibers. Between the secretory cells are sinusoidal capillaries. Sinusoids are lined by fenestrated endothelial cells with diaphragms.

The secretory epithleial cells divided into chromophobes and chromophils by their histologic staining properties and are approximately evenly distributed in the anterior pituitary. Chemophobes are small round cells with very little cytoplasm and pale staining. These cells appear to be non-secretory, have few specific staining granules and are thought to represent a degranulated phase of the secretory epithelia cells. Chemophobes are common sources of tumors.

Chromophils are larger than chromophobes and are further subdivided into acidophils and basophils. Acidophils or Alpha cells make up approximately 40% of secretory epithelial cells and are densely stinging with cytoplasm packed with small granules. There are two types of acidophils: somatotrophs which secrete somatotrophin (GH), and mammotrophs which secrete prolactin (LTH). Basophils or Beta cells make up 10% of secretory epithelial cells and are typically larger than acidophils with smaller, less numberous cytoplasmic granules. There are three types of basophils: thyrotrophs which secrete thyroid stimulating hormone (TSH), gonadotrophs which secrete follicle stimulation hormone (FSH) and leutinizing hormone (LH), and corticotrophs which secrete pro-opiomalanocortin. Thyrotrophs are typically scatterd throughout the parenchyma some distance from sinusoidal capillaries. Pro-opiomalanocortin is cleaved into several smaller peptide products, including adenocorticotrophic hormone, beta-endorphin, melanocyte stimulating hormone, and beta-lipotrophin.


 * **Secretory Cell Type** || **Secretory Cell** || **Hormone Product** ||
 * Acidophilic Chromophil || Somatotrophs || Somatotrophin (GH) ||
 * Acidophilic Chromophil || Mammotrophs || Prolactin (LTH) ||
 * Basophilic Chromophil || Thyrotrophs || Thyroid Stimulating Hormone (TSH) ||
 * Basophilic Chromophil || Gonadotrophs || Follicle Stimulating Hormone (FSH) and Leutinizing Hormone (LH) ||
 * Basophilic Chromophil || Corticotrophs || Pro-opiomalanocortin ||

__Somatotrophin__ Stimultes chondrocyte growth and cartilage matrix secretion in developing bones. Deficiency during development leads to long bones not growing and pituitary dwarfism. Overproduction during development results in prolonged bone growth into adulthood and pituitary giantism. Overproduction in adulthood after epiphyseal plate closure results in increased bone production and overgrowth in extremeties (acromegaly). Also regulates the release of other growth promoting compounds such as somatomedins.

__Somatomedins__ Insulin-like growth factors thought to be produced in the liver and released when stimulated by somatotrophin. Somatomedins act to stimulate cartilage growth and play a role in wound healing.

__Prolactin__ Stimulates and maintains the production/secretion of milk in the breasts. Maintains the corpus luteum for progesterone secretion. Hyperplasia of pituitary mammotrophs occurs during pregnancy.

__Thyroid Stimulating Hormone__ Stimulates the biosynthesis and relase of thyroxine and triiodthyronine from the thyroid gland. TSH secretion is under negative feedback control through systemic levels in the blood. Hypophysectomy results in thyroidatrophy; increased TSH leads to hyperthyroidism; thyroidectomy causes increased thyrotrophs.

__Follicle Stimulating Hormone__ In females, it promotes growth of ovarian follicles. In males, it promotes spermatogenesis by stimulating synthesis of androgen binding protein in Sertoli cells.

__Leutinizing Hormone__ In females, it promotes ovulation, maturation of the corpus luteum, and stimulates progesterone secretion form the corpus luteum. In males, it stimulates Leydig cells in the testis to secreted testosterone.

__Pro-opiomalanocortin__ Cleaves into several smaller peptide products, including adenocorticotrophic hormone, beta-endorphin, melanocyte stimulating hormone, and beta-lipotrophin

__Adenocorticotrophic Hormone__ Stimulates release of glucocorticoids from the adrenal cortex.

__Beta-endorphin__ Small opiate-like peptide involved in pain system.

__Melanocyte Stimulating Hormone__ Stimulates melanin synthesis in melanocytes.

__Beta-lipotrophin__ Function in humans may be to stimulate lipolysis.


 * 3. Identify the components of the neurohypophysis.**

The neurohypophysis or posterior pituitary consists of the pars nervosa, median eminence of the tuber cinereum and the infundibular stalk. The pars nervosa consists of a dense capillary plexus, highly-branched non-secretory glial-like cells called pituicytes, and 50,000-100,000 unmyelinated axons of neurosecretory cells arising form the supraoptic and paraventricular regions of the hypothalamus.

Pituicytes have processes that end in close association with capillaries and are thought to serves a nutritive function. There are //no// secretory epithelial cells in the posterior pituitary; the cells bodies are all in the hypothalamus.


 * 4. Describe the two hormones that are liberated from the posterior lobe of the pituitary in terms of their origin, the hypothalamohypophyseal tract, their target organs, and their function.**

There are //no// secretory epithelial cells in the posterior pituitary; the cells bodies are all in the hypothalamus.

Two major hormones are produced by hypothalamic neurosecretory cells and released in the posterior pituitary: Oxytocin and vasopressin.

Oxytocin is synthesized in the paraventricular nucleus of the hypothalamus. It functions to induce peristaltic contractions of the uterine smooth muscle to facilitate parturition. It also induces the contraction of myoepithelial cells of the mammary gland resulting in the excretion of milk from the secretory alveoli.

Vasopression or anti-diuretic hormone, is synthesized primarily in the supraoptic nucleus and functions in promoting water reabsorption through the collecting tubules of the kidney. It also increases blood pressure by promoting contraction of vascular smooth muscle resulting in increased peripheral resistance.

Hormones are delivered to the posterior pituitary gland along the axons of neurosecretory cells in the hypothalamus. Descending axons from the supraoptic and paraventricular nuclei of the hypothalamus gather in the infundibulum and form the hypothalamic hypophyseal tract which terminates in close association with the capillary plexus of the posterior lobe.

The terminals of these axons terminate near fenestrated capillaries where their vesicle bound hormones are secreted by exocytosis. Hormones are bound to neurophysin, a carrier protein and shipped via axoplasmic transport from the soma to the axon terminals. Hormones are released in response to neural impules traveling down these unmyelinated axons to their terminals. Dense aggregates of vesicle-bound hormones cause axon terminals to dilate into Herring bodies.


 * 5. Be able to descibe the signals which trigger the release of pituitary hormones and their feedback regulation.**

Regulation of hormone release from the pars distalis of the anterior pituitary is controlled by the neuroendocrine link between the brain and the endocrine organs.

Hormone release is modulated by specific peptides called “releasing factors” which are produced by neurons in the basal hypothalamus and are known as hypothalamic hypophysiotrophic peptides. These peptides are produced in four specific regions: preoptic, paraventricular, arcuate, and suprachiasmatic regions. Each anterior pituitary hormone has its own associated release promoting peptide in the hypothalamus and, in at least 2 instances, a specific release inhibiting peptides.

Cells in the hypothalamus which produce and secrete these peptides are small unmyelinated neurons that terminate in the fenestrated capillaries of the primary plexus. Secretion of these regulatory hormones is influenced by both neural and hormonal signals.

Following the release of these peptides into the fenestrated capillaries of the primary plexus, they are carried by the portal veins to the secondary plexus in the anterior pituitary where they stimulate/inhibit the secretory epithelial cells to secrete their designated hormone.

Hormones released by the posterior pituitary are controlled by neural impulses traveling down the unmyelinated axons of neurosecretory cells in the supraoptic and paraventricular regions of the hypothalamus to their terminals in the posterior pituitary.

Pituitary hormones are regulated via feedback mechanisms. Posterior pituitary hormones (oxytocin, vasopressin) are regulated by first order negative feedback where the neurohypophyseal hormones acts on a non-endocrine target organ and levels of this hormone or the products of the target organ feed back to the posterior pituitary to regulate further hormone release.

Anterior pituitary hormones can be regulated by second or third order negative feedback. In second order feedback, the hypothalamic releasing factors stimulates release of an adenohypophyseal hormone (somatotrophin, prolactin) which acts on target tissues; the plasma level of the pituitary hormone feeds back to the hypothalamus or pituitary to regulate further hormone release.

In third order feedback, the hypothalamic releasing factor stimulates the secretion of a adenohypophyseal hormone (somatotrophin, TSH, ACTH) which acts on target endocrine organ to secrete its own peripheral hormone. Levels of the peripheral target organ hormone feed back to the pituitary or hypothalamus to regulate further hormone release.


 * 6. Describe the overall histology of the pineal gland and the hormones produced by this gland.**

The pineal gland (epiphysis cerebri) is a flattened conical gland attached to the midline of the superior surface of the diencephalon of the CNS. It is encapsulated by the connective tissue pia of the CNS which penetrate the parenchyma as trabeculae. The pineal gland is populated by pinealocytes and glial cells.

Pinealocytes have a basophilic cytoplasm with long cytoplasmic processes that end in a bulb-like expansion in close proximity to capillaries. These extensions have small dense core vesicles similar to those seen in catacholameinergic neurons which are exocytosed into the capillaries. Pinealocytes typically have a large oval nucleus and clearly distinguishable nucleoli. They have dense rods or lamellae near the cell membrane which resemble the presynaptic ribbon apparatus often seen in the sensory tranducers of the eye and ear. The number, density, and length of these lamellae exhibit a diurnal cycle.

Glial cells or interstitial cells resemble the astrocyte support cells of the CNS structurally and immunochemically. The pineal gland contains small aggregates of brain sand (calcium phosphate, calcium bicarbonate) that is radiopaque and was once used to clinically determine brain compression and space-occupying lesions of the CNS.

Pinealocytes secrete melatonin which they synthesize from serotonin. The activity of melatonin is unclear but appears to cause retention of pigment granules in melanophores in the skin, having the opposite effect of melanocyte stimulating hormone (MSH). Melatonin also exhibits anti-gonadotrophic effects and may inhibit FSH and LH activity and may be important in seasonal breading animals to coordinate reproduction with seasonal variations in day length. Lastly, melatonin may have some functions as a free radical scavenger and anti-oxidant in some tissues.

Melatonin is released during the dark cycle and is inhibited by light. Melatonin inhibits growth and metastasis of some tumors. Overproduction of melatonin may be involved in seasonal afflictive disorder and appear to be involved in regulating biorhythm and the sleep/wake cycle.