Endocrine Glands
PITUITARY GLAND (HYPOPHYSIS)The pituitary gland , or hypophysis, lies below the brain in a small cavity on the sphenoid bone, the sella turcica. The pituitary is formed in the embryo partly from the developing brain and partly from the developing oral cavity.
The neural component is the neurohypophyseal bud growing down from the floor of the future diencephalon as a stalk (or infundibulum) that remains attached to the brain. The oral component arises as an outpocketing of ectoderm from the roof of the primitive mouth and grows cranially, forming a structure called the hypophyseal ( Rathke ) pouch . The base of this pouch eventually constricts and separates from the pharynx. Its anterior wall then thickens greatly, reducing the pouch’s lumen to a small fissure.
Because of its dual origin, the pituitary actually consists of two glands—the posterior neurohypophysis and the anterior adenohypophysis —united anatomically but with different functions. The neurohypophysis retains many histologic features of brain tissue and consists of a large part, the pars nervosa , and the smaller infundibulum stalk attached to the hypothalamus at the median eminence. The adenohypophysis , derived from the oral ectoderm, has three parts: a large pars distalis or anterior lobe; the pars tuberalis, which wraps around the infundibulum; and the thin pars intermedia adjacent to the posterior pars nervosa.
The Hypothalamic-Hypophyseal Tract & Blood Supply
The pituitary gland’s neural connection to the brain and its blood supply are both of key importance for its function.
Embryologically, anatomically, and functionally, the pituitary gland is connected to the hypothalamus at the base of the brain. In addition to the vascular portal system carrying small regulatory peptides from the hypothalamus to the adenohypophysis, a bundle of axons called the hypothalamic-hypophyseal tract courses into the neurohypophysis from two important hypothalamic nuclei. The peptide hormones ADH (antidiuretic hormone) and oxytocin are synthesized by large neurons in the supraoptic and the paraventricular nuclei, respectively. Both hormones undergo axonal transport and accumulate temporarily in the axons of the hypothalamic-hypophyseal tract before their release and uptake by capillaries branching from the inferior arteries.
The blood supply derives from two groups of vessels coming off the internal carotid artery and drained by the hypophyseal vein.
The superior hypophyseal arteries supply the median eminence and the infundibular stalk; the inferior hypophyseal arteries provide blood mainly for the neurohypophysis.
The superior arteries divide into a primary plexus of fenestrated capillaries that irrigate the stalk and median eminence. These capillaries then rejoin to form venules that branch again as a larger secondary capillary plexus in the adenohypophysis. These vessels make up the hypothalamic-hypophyseal portal system that has great importance because it carries neuropeptides from the median eminence the short distance to the adenohypophysis where they either stimulate or inhibit hormone release by the endocrine cells there.
Adenohypophysis (Anterior Pituitary)
The three parts of the adenohypophysis are derived embryonically from the hypophyseal pouch.
Pars Distalis The pars distalis accounts for 75% of the adenohypophysis and has a thin fibrous capsule. The main components are cords of well-stained endocrine cells interspersed with fenestrated capillaries and supporting reticular connective tissue. Common stains suggest two broad groups of cells in the pars distalis with different staining affinities: chromophils and chromophobes.
Chromophils are secretory cells in which hormone is stored in cytoplasmic granules. They are also called basophils and acidophils, based on their affinities for basic and acidic dyes, respectively.
Subtypes of basophilic and acidophilic cells are identified by their granular morphology in the TEM or more easily by immunohistochemistry. Specific cells are usually named according to their hormone’s target cells. Acidophils secrete either growth hormone (somatotropin) or prolactin and are called somatotrophs and lactotrophs (or somatotropic cells and lactotropic cells), respectively. The basophilic cells are the corticotrophs, gonadotrophs, and thyrotrophs, with target cells in the adrenal cortex, gonads, and thyroid gland, respectively. Somatotrophs typically constitute about half the cells of the pars distalis in humans, with thyrotrophs the least abundant.
With two exceptions, each type of anterior pituitary cell makes one kind of hormone. Gonadotrophs secrete two different glycoproteins:
follicle-stimulating hormone (FSH) and luteinizing hormone (LH; called interstitial cell-stimulating hormone [ICSH] in men). The main protein synthesized in corticotrophs is pro-opiomelanocortin (POMC), which is cleaved posttranslationally into the polypeptide hormones adrenocortical trophic hormone (ACTH) and b-lipotropin (b-LPH). Hormones produced by the pars distalis have widespread functional activities. They regulate almost all other endocrine glands, ovarian function and sperm production, milk production, and the metabolism of muscle, bone, and adipose tissue.
Chromophobes stain weakly, with few or no secretory granules, and also represent a heterogeneous group, including stem and undifferentiated progenitor cells as well as any degranulated cells present.
Pars Tuberalis The pars tuberalis is a smaller funnel-shaped region surrounding the infundibulum of the neurohypophysis . Most of the cells of the pars tuberalis are gonadotrophs.
Pars Intermedia The pars intermedia is a thin zone of basophilic cells between the pars distalis and the pars nervosa of the neurohypophysis, which is often invaded by basophils.
The pars intermedia develops from the dorsal wall of the hypophyseal pouch and usually contains colloid-filled cysts of various sizes that represent remnants of that structure’s lumen.
Neurohypophysis (Posterior Pituitary)
The neurohypophysis consists of the pars nervosa and the infundibular stalk and, unlike the adenohypophysis, does not contain the cells that synthesize its two hormones. It is composed of neural tissue, containing some 100,000 unmyelinated axons of large secretory neurons with cell bodies in the supraoptic and paraventricular nuclei of the hypothalamus. Also present are highly branched glial cells called pituicytes that resemble astrocytes and are the most abundant cell type in the posterior pituitary.
The secretory neurons have all the characteristics of typical neurons, including the ability to conduct an action potential, but have larger-diameter axons and well-developed synthetic components related to the production of the 9-amino acid peptide hormones antidiuretic hormone (ADH)—also called arginine vasopressin—and oxytocin.
Transported axonally into the pars nervosa, these hormones accumulate in axonal dilations called neurosecretory bodies or Herring bodies, visible in the light microscope as faintly eosinophilic structures. The neurosecretory bodies contain membrane-enclosed granules with either oxytocin or ADH bound to carrier proteins called neurophysin I and II, respectively.
Adrenal Glands
The adrenal (or suprarenal) glands are paired organs lying near the superior poles of the kidneys, embedded in the perirenal adipose tissue. They are flattened structures with a half-moon shape, their weight and size vary with the age and physiologic condition of the individual.
Adrenal glands are each covered by a dense connective tissue capsule that sends thin trabeculae into the gland’s parenchyma. The stroma consists mainly of reticular fibers supporting the secretory cells and microvasculature. Each gland has two concentric regions: a yellowish adrenal cortex and a reddish brown central adrenal medulla. The adrenal cortex and medulla can be considered two different organs with distinct embryonic origins, functions, and morphologic characteristics that become united during embryonic development. The cortex arises from mesoderm and the medulla from the neural crest. The general histologic appearance of the adrenal gland is typical of an endocrine gland in which cells of both cortex and medulla are grouped in cords along wide capillaries.
Adrenal Cortex
Cells of the adrenal cortex have characteristic features of steroid- secreting cells: acidophilic cytoplasm rich in lipid droplets, with central nuclei.Steroid hormones are not stored in granules like proteins or undergo exocytosis. As small lipid-soluble molecules, steroids diffuse freely from cells through the plasma membrane. The adrenal cortex has three concentric zones in which the cords of epithelial steroid-producing cells are arranged somewhat differently and which synthesize different classes of steroid hormones:
■ The zona glomerulosa, immediately inside the capsule and comprising about 15% of the cortex, consists of closely packed, rounded or arched cords of columnar or pyramidal cells with many capillaries. The steroids made by these cells are called mineralocorticoids because they affect uptake of Na+, K+, and water by cells of renal tubules, the principal product is aldosterone.
■ The middle zona fasciculata, occupies 65% to 80% of the cortex and consists of long cords of large polyhedral cells, one or two cells thick, separated by fenestrated sinusoidal capillaries. The cells are filled with lipid droplets and appear vacuolated in routine histologic preparations. These cells secrete glucocorticoids, especially cortisol.
■ The innermost zona reticularis comprises about 10% of the cortex and consists of smaller cells in a network of irregular cords interspersed with wide capillaries. The cells are usually more heavily stained than those of the other zones because they contain fewer lipid droplets and more lipofuscin pigment. Cells of the zona reticularis also produce cortisol but primarily secrete the weak androgens, including dehydroepiandrosterone (DHEA) that is converted to testosterone in both men and women. Secretion by these cells is also stimulated by ACTH with regulatory feedback.
Adrenal Medulla
The adrenal medulla is composed of large, pale-staining polyhedral cells arranged in cords or clumps and supported by a reticular fiber network. A profuse supply of sinusoidal capillaries intervenes between adjacent cords and a few parasympathetic ganglion cells are present. Medullary parenchymal cells, known as chromaffin cells, arise from neural crest cells, as do the postganglionic neurons of sympathetic and parasympathetic ganglia. Chromaffin cells can be considered modified sympathetic postganglionic neurons, lacking axons and dendrites and specialized as secretory cells. Unlike cells of the adrenal cortex, chromaffin cells contain many electron-dense granules for storage and secretion of catecholamines, either epinephrine or norepinephrine, The granules of epinephrine-secreting cells are less electron-dense and generally smaller than those of norepinephrine-secreting cells.Medullary chromaffin cells are innervated by cholinergic endings of preganglionic sympathetic neurons, which trigger hormone release.
Thyroid Gland
The thyroid gland, located anterior and inferior to the larynx, consists of two lobes united by an isthmus. It originates in early embryonic life from the foregut endoderm near the base of the developing tongue. It synthesizes the thyroid hormones thyroxine (tetra-iodothyronine or T4) and triiodothyronine (T3), which help control the basal metabolic rate in cells throughout the body, as well as the polypeptide hormone calcitonin.The parenchyma of the thyroid is composed of millions of rounded epithelial thyroid follicles of variable diameter, each with simple epithelium and a central lumen densely filled with gelatinous acidophilic colloid. The thyroid is the only endocrine gland in which a large quantity of secretory product is stored. Moreover, storage is outside the cells, in the colloid of the follicle lumen, which is also unusual. There is sufficient hormone in follicles to supply the body for up to 3 months with no additional synthesis. Thyroid colloid contains the large glycoprotein thyroglobulin, the precursor for the active thyroid hormones.
The thyroid gland is covered by a fibrous capsule from which septa extend into the parenchyma, dividing it into lobules and carrying blood vessels, nerves, and lymphatics. Follicles are densely packed together, separated from one another only by sparse reticular connective tissue, although this stroma is very well vascularized with fenestrated capillaries for transfer of released hormone to the blood. The follicular cells, or thyrocytes, range in shape from squamous to low columnar, their size and other features varying with their activity that is controlled by thyroid-stimulating hormone (TSH) from the anterior pituitary. Active glands have more follicles of low columnar epithelium; glands with mostly squamous follicular cells are hypoactive.
Thyrocytes have apical junctional complexes and rest on a basal lamina. The cells exhibit organelles indicating active protein synthesis and secretion, as well as phagocytosis and digestion. The nucleus is generally round and central. Basally the cells are rich in rough ER and apically, facing the follicular lumen, are Golgi complexes, secretory granules, numerous phagosomes and lysosomes, and microvilli.
Another endocrine cell type, the parafollicular cell, or C cell, is also found inside the basal lamina of the follicular epithelium or as isolated clusters between follicles. Derived from the neural crest, parafollicular cells are usually somewhat larger than follicular cells and stain less intensely. They have numerous small granules containing calcitonin.
Secretion of calcitonin is triggered by elevated blood Ca2+ levels and it inhibits osteoclast activity, but this function in humans is less important than the roles of parathyroid hormone and vitamin D in the regulation of normal calcium homeostasis.
Parathyroid Glands
The parathyroid glands are four small ovoid masses located on the back of the thyroid gland, usually embedded in the larger gland’s capsule. The microvasculature of each arises from the inferior thyroid arteries. Each parathyroid gland is contained within a thin capsule from which septa extend into the gland. A sparse reticular stroma supports dense elongated clusters of secretory cells.
The parathyroid glands are derived from the embryonic pharyngeal pouches—the superior glands from the fourth pouch and the inferior glands from the third pouch. Their migration to the developing thyroid gland is sometimes misdirected so that the number and locations of the glands are somewhat variable. Up to 10% of individuals may have parathyroid tissue attached to the thymus, which originates from the same pharyngeal pouches.
The endocrine cells of the parathyroid glands, called principal (chief) cells, are small polygonal cells with round nuclei and pale-staining, slightly acidophilic cytoplasm. Irregularly shaped cytoplasmic granules contain the polypeptide parathyroid hormone (PTH), an important regulator of blood calcium levels.
With increasing age, many secretory cells are replaced with adipocytes, which may constitute more than 50% of the gland in older people.
Much smaller populations of oxyphil cells, often clustered, are sometimes also present in parathyroid glands, more commonly in older individuals. These are much larger than the principal cells and are characterized by very acidophilic cytoplasm filled with abnormally shaped mitochondria. Some oxyphil cells show low levels of PTH synthesis, suggesting that these cells are transitional derivatives of principal cells.
Pineal Gland
The pineal gland, also known as the epiphysis cerebri, regulates the daily rhythms of bodily activities. A small, pine cone-shaped organ, the pineal gland develops from neuroectoderm in the posterior wall of the third ventricle and remains attached to the brain by a short stalk.The pineal gland is covered by connective tissue of the pia mater, from which septa containing small blood vessels emerge and subdivide variously sized lobules. Prominent and abundant secretory cells called pinealocytes have slightly basophilic cytoplasm and irregular euchromatic nuclei. Ultrastructurally pinealocytes are seen to have secretory vesicles, many mitochondria, and long cytoplasmic processes extending to the vascularized septa, where they end in dilatations near capillaries, indicating an endocrine function, The pinealocytes produce melatonin.
Unmyelinated sympathetic nerve fibers enter the pineal gland and end among pinealocytes, with some forming synapses. Melatonin release from pinealocytes is promoted by darkness and inhibited by daylight. The resulting diurnal fluctuation in blood melatonin levels induces rhythmic Changes in the activity of the hypothalamus, pituitary gland, And other endocrine tissues that characterize the circadian (24 hours, day/night) rhythm of physiological functions and Behaviors.
In humans and other mammals, the cycle of light And darkness is detected within the retinas and transmitted To the pineal via the retinohypothalamic tract, the suprachiasmatic Nucleus, and the tracts of sympathetic fibers entering the Pineal. The pineal gland acts, therefore, as a neuroendocrine Transducer, converting sensory input regarding light and darkness Into variations in many hormonal functions.
The pineal gland also has interstitial glial cells that are Modified astrocytes, staining positively for glial fibrillary Acidic protein, which represent about 5% of the cells. These Have elongated nuclei more heavily stained than those of Pinealocytes and are usually found in perivascular areas and Between the groups of pinealocytes.
A characteristic feature of the pineal gland is the presence Of variously sized concretions of calcium and magnesium Salts called corpora arenacea, or brain sand, which form As extracellular protein deposits become mineralized. Such Concretions appear during childhood and gradually increase In number and size with age, with no apparent effect on the Gland’s function.