Endocrine System PDF

Endocrine System Fevziye Figen Kaymaz M.D., Ph.D. Prof. of Histology & Embryology [email protected] 1 Learning Goals PITUITARY GLAND (HYPOPHYSIS) ADRENAL GLANDS PANCREATIC ISLETS THYROID GLAND PARATHYROID GLANDS PINEAL GLAND...

Endocrine System Fevziye Figen Kaymaz M.D., Ph.D. Prof. of Histology & Embryology [email protected] 1 Learning Goals PITUITARY GLAND (HYPOPHYSIS) ADRENAL GLANDS PANCREATIC ISLETS THYROID GLAND PARATHYROID GLANDS PINEAL GLAND 2 PITUITARY GLAND (HYPOPHYSIS) weighs about 0.5 g in adults Dimensions 10 x13 x 6 mm. The pituitary gland is composed of an anterior part and a posterior part that is directly attached to the hypothalamus region of the brain by an infundibular stalk. The gland occupies a fossa of the sphenoid bone called the sella turcica 3 The anterior lobe of the pituitary gland consists of the pars distalis, the pars tuberalis and the pars intermedia; The posterior lobe consists of the infundibulum and pars nervosa. Adenohypophysis (Anterior Pituitary) The three parts of the adenohypophysis are derived embryonically from the hypophyseal pouch 1- Pars Distalis 75% of the adenohypophysis a thin fibrous capsule. two groups of cells : 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. 5  Gonadotrophs secrete two different glycoproteins: follicle- stimulating hormone (FSH) and luteinizing hormone The main protein synthesized in corticotrophs is 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. 6 2- 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. 3- 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 and usually contains colloid-filled cysts of various sizes 7 Pars distalis. pars intermedia AC asidofil, Bas bazofiller, Ch kromofoblar CF colloid filled follicles Pars distalis. pars intermedia (PI) acidophils (A), Basophils (B) pars distalis (PD) small cysts (Cy) Chromophobes (C) capillaries (Cap), 10 11 12 Neurohypophysis (Posterior Pituitary) The neurohypophysis consists of the pars nervosa and the infundibular stalk 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 13  ADH is released in response to increased blood tonicity, sensed by osmoreceptor cells in the hypothalamus, which then stimulate ADH synthesis in supraoptic neurons. ADH increases the permeability of the renal collecting ducts to water so that more water is reabsorbed from the filtrate in these tubules and osmotic balance of body fluids is restored Oxytocin stimulates contraction of the myoepithelial cells of uterine smooth muscle during childbirth and of alveoli and ducts in the mammary glands. A nursing infant induces oxytocin secretion by stimulating sensory tracts that act on the hypothalamus in a neurohormonal reflex producing rapid ejection of milk. 14 15 ADRENAL GLANDS (suprarenal glands) The adrenal (or suprarenal) glands are paired organs lying near the superior poles of the kidneys, embedded in the pararenal adipose tissue and fascia. They are flattened structures with a half-moon shape, about 4-6-cm long, 1-2-cm wide, and 4- 6-mm thick in adults. they weigh about 8 g, but their weight and size vary with the age and physiologic condition of the individual. The parenchymal cells of the adrenal cortex are controlled in part by the anterior lobe of the pituitary gland and function in regulating metabolism and maintaining normal electrolyte balance. 16  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 17 18  The adrenal cortex has three concentric zones in which the cords of epithelial steroid-producing cells are arranged somewhat different and which synthesize different classes of steroid hormones 1- zona glomerulosa near the capsule, 2- zona fasciculata (the thickest layer), 3- zona reticularis. 19  zona glomerulosa 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 major regulator of salt balance, which acts to stimulate Na+ reabsorption in the distal convoluted tubules. Aldosterone secretion is stimulated primarily by angiotensin II and also by an increase in plasma K+ concentration, but only weakly by ACTH. 20 zona fasciculata The middle zona fasciculata, occupies 65%-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, which affect carbohydrate metabolism by stimulating gluconeogenesis in many cells and glycogen synthesis in the liver. Cortisol also suppresses many immune functions and can induce fat mobilization and muscle proteolysis. Secretion is controlled by ACTH with negative feedback proportional to the concentration of circulating glucocorticoids. Small amounts of weak androgens are also produced here. 21 zona reticularis 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. 22 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. 23  Unlike cells of the adrenal cortex, chromaffin cells contain many electron-dense granules, 150-350 nm in diameter, 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 Both catecholamines, together with Ca2+ and ATP, are bound in granular storage complexes with 49-kDa proteins called chromogranins. ATP + Ca2 +epine + norepin 24 TEM reveals that the granules of norepinephrine-secreting cells (NE) are more electron-dense than those of cells secreting epinephrine (E), which is due to the chromogranins binding the catecholamines. Most of the hormone produced is epinephrine, which is only made in the adrenal medulla. 25 26 PANCREATIC ISLETS (Endocrine Pancreas) The pancreatic islets (islets of Langerhans) are compact spherical or ovoid masses of endocrine cells embedded within the acinar exocrine tissue of the pancreas. Most islets are 100-200 μm in diameter and contain several hundred cells, but some have only a few cells. The pancreas has more than 1 million islets, mostly in the gland’s narrow tail region, but they only constitute 1%-2% of the organ’s total volume. A very thin reticular capsule surrounds each islet, separating it from the adjacent acinar tissue. Pancreatic islets have the same embryonic origin as the pancreatic acinar tissue: in epithelial outgrowths from endoderm of the developing gut. 27 28  The cells of islets are polygonal or rounded, smaller, and more lightly stained than the surrounding acinar cells, arranged in cords separated by fenestrated capillaries. Routine stains or trichrome stains show that most islet cells are acidophilic or basophilic with fine cytoplasmic granules. Ultrastructural features are those of active polypeptide-secreting cells, with secretory granules that vary in size, morphology, and electron density from cell to cell. 29  The major islet cells are most easily identified and studied by immunohistochemistry: α or A cells secrete primarily glucagon and are usually located peripherally. β or B cells produce insulin (L. insula, island), are the most numerous, and are located centrally. δ or D cells, secreting somatostatin, are scattered and much less abundant. 30  A minor fourth cell type, more common in islets located within the head of the pancreas, are PP cells, which secrete pancreatic polypeptide. Pancreatic islets also normally contain a few enterochromaffin cells, like those of the digestive tract, which are also scattered in the pancreatic acini and duct and which secrete other hormones affecting the digestive system. 31 32 THYROID GLAND The thyroid gland, located anterior and inferior to the larynx, consists of two lobes united by an isthmus It synthesizes the thyroid hormones +thyroxine (tetra-iodothyronine or T4) +tri-iodothyronine (T3), +calcitonin. It originates in early embryonic life from the foregut endoderm near the base of the developing tongue. 33  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 outside the cells, in the colloid C capsule S septum There is sufficient hormone in follicles L Lumen to supply the body for up to 3 months C C cell with no additional synthesis. Thyroid colloid contains the large glycoprotein thyroglobulin, the precursor for the active thyroid hormones. 34  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. 35  Follicular cells (thyrocytes) shape from squamous to low columnar their size and other features varying with their activity, which 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. The nucleus is generally round and central. The cells exhibit organelles indicating active protein synthesis and secretion, as well as phagocytosis and digestion. 36 Parafollicular cell -C cell- endocrine cell type, found inside the basal lamina of the follicular epithelium or as isolated clusters between follicles Derived from the neural crest, larger than follicular cells and stain less intensely. Secrete calcitonin Secretion of calcitonin is triggered by elevated blood Ca2+ levels, and it inhibits osteoclast activity, Parafollicular cell -C cell- have a smaller amount of rough ER, large Golgi complexes, and numerous small (100-180 nm in diameter) granules containing calcitonin 37 Goiter Chronic dietary iodine deficiencies inhibit thyroid hormone production, causing thyrotropic cells of the anterior pituitary gland to produce excess TSH. This leads to excessive growth of thyroid follicles and enlargement of the thyroid gland, a condition known as goiter. 38  Graves disease an autoimmune disorder antibodies produce chronic stimulation of the follicular cells and release of thyroid hormones (hyperthyroidism) causes a hypermetabolic state marked by weight loss, nervousness, sweating, heat intolerance, and other features. 39 Hypothyroidism reduced thyroid hormone levels, can be caused by local inflammation (thyroiditis) or inadequate secretion of TSH by the anterior pituitary gland and is often manifested by tiredness, weight gain, intolerance of cold, and decreased ability to concentrate. 40 41 PARATHYROID GLANDS four small ovoid masses each 3 × 6 mm a total weight of about 0.4 g. They are located on the back of the thyroid gland, usually embedded in the gland’s capsule 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. 42 principal (chief) cells endocrine cells of the parathyroid glands small polygonal cells with round nuclei and pale- staining, slightly acidophilic cytoplasm Irregularly shaped cytoplasmic granules contain the 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. 43 PTH has three major targets: 1- Osteoblasts respond to PTH by producing an osteoclast-stimulating factor, which increases the number and activity of osteoclasts. The resulting resorption of the calcified bone matrix and release of Ca2+ increase the concentration of circulating Ca2+, which suppresses PTH production. The effect of PTH on blood levels of Ca2+ is thus opposite to that of calcitonin. 2- In the distal convoluted tubules of the renal cortex, PTH stimulates Ca2+ reabsorption (and inhibits phosphate reabsorption in the proximal tubules). 3- PTH also indirectly increases the Ca2+ absorption in the small intestine by stimulating vitamin D activation. 44 PTH Increases blood calcium level in three ways: (1) promotes calcium release from bone (acting on osteoblasts via RANK-RANKL signaling system, it increases the relative number of osteoclasts; (2) acts on the kidney to stimulate calcium reabsorption by the distal tubule while inhibiting phosphate reabsorption in the proximal tubule; (3) increases formation of hormonally active 1,25-dihydroxycholecalciferol (1,25- [OH]2 vitamin D3) in the kidney, which promotes tubular reabsorption of calcium 45 oxyphil cells Much smaller populations often clustered, 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. Accumulating with age, oxyphil cells are degenerated derivatives of principal cells, with some still exhibiting low levels of PTH synthesis. 46 47 PINEAL GLAND The pineal gland, also known as the epiphysis cerebri, regulates the daily rhythms of bodily activities. A small, pine cone-shaped organ, approximately 5-8 mm by 3-5 mm, 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. 48  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. These cells produce melatonin, a low molecular-weight tryptophan derivative. Unmyelinated sympathetic nerve fibers enter the pineal gland and end among pinealocytes, with some forming synapses. 49  (a) The micrograph shows a group of pinealocytes surrounded by septa (S) containing venules (V) and capillaries (arrows). Also seen is an extracellular mineral deposit called a corpusarenaceum (CA) of unknown physiologic significance but an excellent marker for the pineal. (b) At higher magnification the numerous large pinealocytes (P) with euchromatic nuclei can be compared to much fewer astrocytes (A) that have darker, more elongated nuclei and are located mainly within septa and near small blood vessels (V). Capillaries (arrow) are not nearly as numerous as in other endocrine glands. At the lower left is a port of a very large corpus arenaceum (CA), the calcified structures also known as brain sand. Along the septa run unmyelinated tracts of sympathetic fibers, associated indirectly with photoreceptive neurons in the retinas and running to the pinealocytes to stimulate melatonin release in periods of darkness. Levels of circulating melatonin are one factor determining the diurnal rhythms of hormone release and physiologic activities throughout the 50 body  Melatonin release from pinealocytes is promoted by darkness and inhibited by daylight. The resulting diurnal fluctuation in blood melatonin levels induces rhythmicchanges 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. 51  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. 52  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. 53  A characteristic feature of the pineal gland is the presence of corpora arenacea, or brain sand. mineralization of calcium and magnesium salts by extracellular protein deposits Such accumulations occur in childhood and increase in number and size with age, without a pronounced effect on the function of the gland. 54 55