| The Endocrine System
The endocrine system functions as a means of communication among the different cells and organs of the body. The other major communications system is the nervous system. In contrast to the nervous system, the endocrine system elicits a slower response, but its effects are of longer duration. The cells of endocrine organs secrete and release hormones, which are carried in the bloodstream to their target cells in widely separated organs and tissues. The endocrine system is therefore a ductless secretory system. All endocrine organs are richly supplied with blood vessels.The hormones of the endocrine system are chemically divided into several categories. (1) The steroid hormones are derived from cholesterol and are produced by the gonads and the adrenal cortex. (2) Most hormones are small peptides, or proteins or glycoproteins. Such hormones are produced by the hypothalamus, pituitary (hypophysis), parathyroid, pancreas, and the enteroendocrine cells of the gastrointestinal tract and lungs. (3) The catecholamines of the adrenal medulla, epinephrine and norepinephrine, are derivatives of a single amino acid, tyrosine. (4) The thyroid hormones thyroxine (T4) and T3 are derived from the oxidative coupling of two molecules of modified, iodinated tyrosine. (The thyroid hormones are sometimes lumped with category 2 or 3). The endocrine system and the nervous system function in conjunction with one another, and most biological phenomena are under the overlapping control of both systems. The nervous and endocrine elements are generally regarded as constituting a single neuroendocrine system. In the laboratory sessions, we look at the pituitary gland, adrenal gland, endocrine pancreas, thyroid and parathyroid glands.
The Pituitary Gland
The pituitary gland, or hypophysis, is a composite gland derived from two sources. The anterior pituitary, or adenohypophysis, is derived from an outpocketing of the oral ectoderm, called Rathke's pouch, which grows upward toward the brain. The posterior pituitary, or neurohypophysis, is derived from the downgrowth of the neuroectoderm of the floor of the third ventricle; this downgrowth is called the infundibulum. (The embryonic brain compartment enclosing the third ventricle is called the diencephalon, which gives rise to thalamus and hypothalamus). The neurohypophysis (infundibulum) consists of the median eminence (part of the floor of the third ventricle), the infundibular stalk and the pars nervosa (or neural lobe). The adenohypophysis consists of the pars distalis, the pars tuberalis and the pars intermedia. The pars distalis, which constitutes by far the greater part of the adenopypophysis, arises from anterior wall of Rathke’s pouch which becomes enlarged. A dorsal extension of the pars distalis, called the pars tuberalis, surrounds the infundibular stalk. The vestigial (in humans) pars intermedia is the thin remnant of the posterior wall of Rathke’s pouch. It lies against the pars nervosa, separated from the pars distalis by colloid-containing vesicles, called Rathke’s cysts, which are the remnants of the cavity of Rathke's pouch.
The pars distalis does not receive a substantial arterial blood supply of its own. The superior hypophysial arteries supply the median eminence, pars tuberalis and infundibular stem, and give rise to fenestrated capillaries (the primary capillary plexus). These capillaries drain into portal veins called the hypophyseal portal veins, which run along the pars tuberalis and give rise to another fenestrated capillary plexus (the secondary capillary plexus) in the pars distalis. The activity of the secretory cells of the adenohypophysis is controlled by releasing hormones and inhibiting hormones made by neurosecretory neurons in various nuclei in the hypothalamus. The axons of these neurosecretory neurons release their products into the median eminence from where they are carried to the pars distalis via the hypophyseal portal veins. The pars nervosa of the neurohypophysis is supplied by the inferior hypophyseal arteries. Venous drainage from the whole pituitary occurs via hypophyseal veins which empty into the cavernous sinus. (You may refer to lecture notes and textbooks for more details (including pictures) on the anatomy and blood supply of the pituitary. You should also understand how the release of hormones from the adenohypophysis is regulated through the stimulatory and inhibitory hormones of the hypothalamus. You should be aware that both the pituitary hormones themselves and the hormones of their target organs exert feedback effects. The functions of the pituitary hormones are not discussed here.)
The adenohypophysis (anterior pituitary) consists of glandular epithelial tissue arranged in cords and clumps of cells. Abundant fenestrated capillaries run between the clusters of these secretory cells. The hormones produced by the secretory cells are released into the capillaries. The cells of the pars distalis are divided about evenly into chromophobes and chromophils. Chromophobes take up little or no stain, and are inactive (transiently degranulated secretory cells) or undifferentiated cells. (One group of chromophobes may produce ACTH.) Chromophils are subdivided into acidophils (40% of all cells) and basophils (10% of all cells). Acidophils stain with acid dyes. Basophils stain with basic dyes and with the periodic acid-Schiff (PAS) reaction due to the glycoprotein in the secretory granules. Acidophils make prolactin (also called lactogenic hormone) and growth hormone, GH (also called somatotropic hormone, STH). Basophils make the two gonadotropic hormones follicle-stimulating hormone and luteinizing hormone (FSH and LH), thyroid-stimulating hormone (TSH), and adrenocorticotrophic hormone (ACTH). The hormones produced by the cells of the anterior pituitary can be grouped into three families: the somatomammotropin, glycoprotein and POMC families. The two hormones made by acidophils, prolactin and growth hormone, belong to the somatomammotropin family, which also includes the placental hormone, placental lactogen (or placental sommatomammotropin). These hormones are closely related single chain protein hormones that share growth promoting and lactogenic activities. They are believed to have arisen from a common ancestral molecule. FSH, LH and TSH belong to the glycoprotein family, along with the placental hormone chorionic gonadotropin. These hormones are also believed to have a common ancestor. Each hormone consists of two glycopeptide chains, an alpha and a beta chain. The alpha chain in each of the four hormones is identical, while the beta chain is unique to each hormone and conveys receptor binding and biological specificity. ACTH is part of the pro-opiomelanocortin (POMC) family. A precursor molecule, POMC, is broken into three fragments, an N-terminal fragment, ACTH and beta-LPH. In some species, there can be further cleavage of the initial fragments to give rise to melanocyte-stimulating hormones (MSH) and endorphins and enkephalins. Most of this further cleavage takes place in the cells of the pars intermedia (which is well-developed in some species). The number and nature of POMC-derived peptides (other than ACTH) released from the human pituitary is still a matter of debate. The different hormones are made by different cells. Lactotropes (or mammotropes) make prolactin, somatotropes make growth hormone, while gonadotropes, thyrotropes, corticotropes make the gonadotropins, TSH and ACTH respectively. Most gonadotropes make both LH and FSH, some synthesize only one or the other. MSH, in those species that have it, is produced in cells called melanotropes. In the laboratory, we do not try to distinguish cells beyond identifying chromophobes, acidophils and basophils. The cells can be identified more specifically using special techniques. Electron microscopy has revealed that the different cell types differ in size and shape, in the size, density and distribution of their secretory granules, and in the development of their organelles. Specific cell types can also be identified by immunohistochemistry and through histophysiological studies.
The pars nervosa of neurohypophysis consists of about 100,000 unmyelinated axons of nerves whose cell bodies lie in two paired nuclei of the hypothalamus, the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). The axons travel through the median eminence and infundibular stalk to reach the pars nervosa. Neurosecretory products produced by the cell bodies in the SON and PVN are contained in axonal swellings called Herring bodies which are always in close proximity to capillaries. There are two neurosecretory products, oxytocin and vasopressin, also called argenine vasopressin (AVP) or anti-diuretic hormone (ADH). Both hormones are nonapeptides (or octapeptides, depending on whether you count the two cysteine molecules as one amino acid or two) that differ in two of their amino acids. The two hormones are produced by separate sets of neurons within the SON and PVN. Each hormone is found in close association with a larger protein called a neurophysin. In response to physiological stimulation, neurophysins are secreted with their hormones into the blood stream where they act as transport proteins. About 25% of the volume of the neurohypophysis consists of cells called pituicytes, which are comparable to astrocytes (a type of neuroglial cell) of the CNS. Their round or oval nuclei are evident in standard histological preparations. Their cytoplasm extends as long processes from their nuclei, but it is not distinguishable from the unmyelinated nerve fibres. In addition to pituicytes, fibroblasts and mast cells are found in the pars nervosa. (You can’t distinguish them.)
The pars intermedia is small in humans and consists of colloid-containing vesicles. The nature of the colloid is unknown. The vesicles are surrounded by cords of small cells that resemble basophils. These cells are also sometimes seen spilling into the pars nervosa. They may be corticotropes. However, the function (if any) of the pars intermedia in humans is not clear. In some animals, it is quite large and produces MSH.
The figures below are made from slide #77 of your collection, the pituitary of a cow. This slide is stained with Masson trichrome, which stains collagen blue.
Two clusters of cells are numbered, #1 contains only chromophobes, #2 contains mainly acidophils, though the label "2" is lying on a chromophobe. Individual acidophils, basophils and chromophobes are also identified.
The Adrenal Gland Origin and Anatomy The adrenal glands are paired triangular glands that lie above the kidney. They are covered in dense connective tissue from which trabeculae extend into the parenchyma carrying blood vessels and nerves. Like the pituitary gland, the adrenal gland consists of two parts with separate embryological origins. The outer part, or cortex, of the adrenal arises from mesoderm and produces steroid hormones. The inner part is called the medulla, and arises from neural crest cells. The cells of the medulla are modified postganglionic sympathetic cells that secrete the catecholamines adrenalin (epinephrine) and noradrenaline (norepinephrine). They are called chromaffin cells because the catecholamines they contain react (stain brown) with chromaffin salts.
The zones of the
adrenal cortex The adrenal cortex is divided into three zones whose names reflect the arrangement of their cells: the zona glomerulosa, the zona fasciculata and the zona reticularis. The zone glomerulosa is a relatively narrow zone that lies immediately below the connective tissue capsule. Its cells are arranged in closely packed ovoid clusters or curved columns which are continuous with the cellular cords of the zona fasciculata. The cells of the zona glomerulosa are comparatively small, therefore the nuclei appear close together. The zona glomerulosa produces mineralocorticoids, chiefly aldosterone. Aldosterone stimulates the resorption of sodium in the distal and collecting tubules of the kidney, in salivary and sweat glands and the gastrointestinal mucosa. In the kidney, it also stimulates the resorption of water and the secretion of potassium. Aldosterone secretion is regulated mainly by levels of electrolytes and by angiotensin II (see brief description of renin-angiotensin system on pg. 613 of Ross et al.). It is not regulated by pituitary ACTH. The size of the zona glomerulosa can change under certain conditions. It increases when dietary sodium is low and decreases when it is high. The zona fasciculata is the middle zone and the largest, constituting about 80% of the cortical volume. Its cells are arranged in long straight cords, one or two cells thick. Abundant capillaries course between the cords of cells. It is the lightest staining zone because of the large size and foamy (spongy) appearance of its cells, giving them the name spongiocytes. In life, the cells are crowded with lipid droplets which serve as reserves of cholesterol esters for the synthesis of steroid hormones. The lipid dissolves away during tissue preparation. Because of the larger size of the cells, the nuclei in this zone are more widely spaced. Binucleate cells are quite common. The steroid hormones produced by the zona fasciculata are chiefly glucocorticoids. In human, the major glucocorticoid is cortisol (also called hydrocortisone). This zone also produces a relatively small amount of sex steroids, principally weak androgens. Its activity is regulated chiefly by ACTH. Glucocorticoids have a very wide range of metabolic functions. They play an essential permissive role in the functioning of the sympatho-adrenal system. They exert a number of actions in carbohydrate metabolism, most of which are catabolic in nature. In homeotherms (birds and mammals) they are involved in maintaining body temperature. They play a role in lactogenesis. They have a major involvement in the setting of circadian rhythms, generally peaking prior to the onset of activity. They have anti-inflammatory effects, cause lysis of lymphocytes and atrophy of lymphatic tissue. They play a major role in response to stress, and long-term stress can lead to muscle wasting and even death. (For more information on these and other actions, consult an endocrinology textbook.) The zona reticularis is the innermost zone of the cortex. It is slightly thicker than the outer zona glomerulosa but constitutes only 5-7% of the cortical volume. Its cells are arranged in anastomosing cords separated by capillaries. They are noticeably smaller than those of the zona fasciculata, and therefore their nuclei are more closely packed. The cells and nuclei also stain more darkly than those of the ZF. The transition from the zona fasciculata to zona reticularis is gradual: the cells in the lower part of the ZF are smaller and darker than the spongiocytes. Like the zona fasciculata, the zona reticularis is mainly under the control of ACTH. Its principal product is weak androgens, it also produces small quantities of glucocorticoids. In females, adrenal androgens are responsible for the growth of pubic and axillary hair at puberty, and postmenopausally may be a source for extragonadal estrogen production. They may also have an influence on libido. In males, the effects of adrenal androgens are negligible in comparison to those of testosterone from the gonads. (The gonads are endocrine organs as well, but are discussed in the Reproductive Block.)
Blood supply of the adrenal
gland The adrenal glands are supplied with blood from the superior, middle and inferior adrenal arteries (arising from the inferior phrenic, aorta, and renal arteries respectively). The adrenal arteries branch to produce many small arteries that penetrate the capsule. In the capsule, these arteries branch to give rise to three main patterns of blood distribution. (1) Capsular capillaries supply the connective tissue of the capsule. (2) Cortical arterioles form a subcapsular plexus that gives rise to anastomosing cortical sinusoidal capillaries which are lined with fenestrated endothelial cells. The cortical sinusoidal capillaries drain into the sinusoids of the medulla, which are also fenestrated. (3) Medullary arterioles pass through the cortex within the trabeculae to bring blood directly to the capillary sinusoids of the medulla. Thus the medulla had two sources of blood supply, a direct supply and blood that has first trickled through the cortex. The medullary sinusoids drain into small medullary veins that join to form the large medullary vein (adrenal vein), which enters the inferior vena cava.
The adrenal medulla The medulla is composed of large epithelioid cells, called chromaffin cells, arranged in small groups or short cords and closely associated with capillaries. The chromaffin cells are innervated by preganglionic fibres of the sympathetic nervous system which release acetylcholine. However, unlike post-ganglionic sympathetic neurons, chromaffin cells develop no processes, but release their product, norepinephrine or epinephrine, directly into the blood. Whether a medullary cell secretes norepinephrine (NE) or epinephrine (E) depends on its location relative to the blood supply. If a chromaffin cell is supplied by arterial blood that goes directly to the medulla, it will produce norepinephrine (as do sympathetic post-ganglionic fibres). If, on the other hand, it is supplied indirectly by blood that has passed through the sinusoids of the cortex, it will produce epinephrine. The glucocorticoids of the adrenal cortex induce the formation of the enzyme phenylethanolamine-N-methyl transferase (PNMT) which converts NE to E. In humans, about 80% of chromaffin cells produce epinephrine, the remainder produce NE. These hormones affect a range of tissues (glandular epithelium, cardiac muscle, smooth muscle of blood vessels, bronchioles and viscera) and mimic the effects of the sympathetic nervous system. Large quantities are released into the blood stream during stress as part of the "fight or flight" response. In addition to the chromaffin cells, the medulla also contains a few ganglion cells, singly or in small groups. They innervate the smooth muscle of the medullary veins.
The images below were all scanned from slide #70 of your collection (adrenal of a young monkey). You will find that it is much easier to recognize the three cortical zones and medulla on this slide than on slide #18 (human adrenal). The section of tissue on slide #18 is much more irregular in shape, and certain components may be missing in some areas. For example, the medulla may be missing and the zona reticularis on one side may go directly into the ZR on the other side. (Look at both slides under the microscope, but go over #70 first or you’ll drive yourself crazy.)
The Endocrine Pancreas
The pancreas is an elongated gland with an expanded head, body and tail. The head lies in the curve of the duodenum, the body crosses the midline of the human body and the tail extends toward the spleen. A thin layer of connective tissue forms an incomplete capsule around the organ. Septa extending from the capsule divide the pancreas into poorly defined lobules. A stroma of loose connective tissue surrounds the lobules. Between lobules, larger blood vessels, nerves and ducts are surrounded by more abundant connective tissue. The pancreas has both an exocrine and an endocrine component. The exocrine pancreas is by far the greater part of the organ. It consists of serous acini that produce a large number of digestive enzymes in an inactive form. These enzymes are stored in the form of zymogen granules at the apical ends of the acinar cells. They are conveyed by ducts to the small intestine. The structure and function of the exocrine pancreas is discussed more fully in the GI Block. The endocrine part is a diffuse organ and constitutes only about 2% of the volume of the pancreas. It consists of distinct masses of cells called islets of Langerhans. When the pancreas is scanned at low power, they appear as pale islands among the serous acini. The islets vary greatly in size, from a few cells to hundreds of cells. They are most numerous in the tail. Pancreatic islets consist of polygonal cells arranged in short irregular cords through which abundant fenestrated capillaries run. The major hormones of the pancreas are insulin and glucagon. Insulin is produced by B cells, which make up 60-70% of the cells in the islets. Glucagon is produced by A cells, which constitute about 15-20% of islet cells. In routine preparations, it is difficult to tell the cell types apart. Sometimes the A cells can be recognized by their darker stain, their more peripheral location, and their flame-like shape. While A cells tend to be at the periphery, they can also be seen more centrally around blood vessels. You may be able to identify A cells on some of the islets you see. Do not expect to be able to identify A cells on every islet you come across. A and B cells, as well as somatostatin-producing D cells (5-10% of islet cells) constitute the principal cell types of the endocrine pancreas. The islets also contain a number of minor cell types, which produce other hormones including pancreatic polypeptide, vasoactive intestinal peptide, secretin, motilin and substance P.
Insulin
Glucagon
Somatostatin
Blood flow in pancreas
The boundaries of the islet are indicated by asterisks. The islets are lighter staining than the surrounding acinar cells, whose apical ends appear darker due to the presence of zymogen granules. Most of the cells within the islet are B cells. A few darker-staining, more flame-shaped, probable A cells are indicated. While the A cells are not spectacular in any of your slides, they can be more easily identified on some slides (and in some islets) than in others. While islets are paler than the acini, they are not the only pale structures. The ducts of the exocrine pancreas are also made of pale-staining cells. Just below the islet, a duct (labelled) is seen emerging from a rather elongated acinus. Other pale cells belonging to ducts can also be seen among the acini. (In the pancreas, the ducts push deep into the acini, and sometimes appear as pale cells, called centroacinar cells, in the middle of the acinus.) Islets can be distinguished from ducts by the fact that they are generally larger, consisting of cords of cells separated by capillaries. Individual cells within an islet are also larger, with identifiable cytoplasm and a darker nucleus. In the labelled duct below the islet, the pale nuclei are about the only part of the cells that can be identified. Larger ducts, with larger cells, are generally surrounded by some connective tissue, which makes them easier to identify (as in Figure 14).
In the exocrine pancreas, the apical ends of the acinar cells stain bright red with zymogen granules, round blue nuclei can be seen at their basal ends.
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