Endocrine Systems 1

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	Basic characteristics of endocrine glands Contrasted with exocrine glands Fenestrated/sinusoidal capillaries Pituitary gland Orientation and terminology Differences between anterior and posterior pituitary Posterior pituitary The 2 hormones Histological features Anterior pituitary Control of release by hypothalamic releasing factors Unusual vascular organization - hypophyseal portal system The 6 major hormones Histological identification of the different hormonal cell types Thyroid gland Thyroid hormone Hierarchical control of thyroid hormone secretion Goiter due to increased TSH secretion by the pituitary Histology of the thyroid gland Unusual mechanism of storage by the thyroid gland Calcitonin Physiological role Histological identification of the parafollicular cells

	Glands are divided into exocrine and endocrine glands. Exocrine glands (e.g., sweat glands) secrete their products onto an epithelial surface through ducts formed by invaginations of epithelial tissue. Endocrine glands lack ducts, and secrete their products (hormones) into the blood, where they travel to distant target organs. To facilitate this process, endocrine glands are profusely supplied with fenestrated/sinusoidal capillaries. The secretory cells of a gland are collectively termed the parenchyma of the gland. The major endocrine glands include the pituitary, thyroid, parathyroid, adrenal, pineal, ovaries, testes and placenta. In addition to the discrete endocrine glands, many organs contain less discrete groups of endocrine cells. In these two lectures we will cover the pituitary, thyroid, parathyroid, adrenal and pineal glands, as well as the Islets of Langerhans of the endocrine pancreas.



	The pituitary is considered the "master gland" of the body. The hormones it releases control the activity of many other glands and tissues. Thus disorders of the pituitary can have multiple symptoms. Pituitary tumors occur, and can be removed surgically.

	The pituitary (hypophysis) consists of 2 major parts: 1) Anterior pituitary (adenohypophysis) pars distalis (anterior lobe) pars tuberalis (nearly surrounds the infundibulum) pars intermedia (thin strip lying between the two lobes) 2) Posterior pituitary (neurohypophysis) pars nervosa (posterior lobe) infundibulum (stalk connecting pars nervosa with the median eminence of the hypothalamus) These two areas differ strikingly in how their secretory products are transported and released into the circulation.

	The pars nervosa consists of the axons and terminals of neurons whose cell bodies are in the hypothalamus. Thus it is a neural structure. The pars distalis, on the other hand, is purely endocrine (no neurons). How does the pituitary come to be comprised of these two different tissue types?

	The two parts of the pituitary have a different embryological origin. The posterior lobe (neurohypophysis) develops from neural ectoderm as a downgrowth of the diencephalon. The anterior lobe (adenohypophysis) originates from oral ectoderm that folds upward to lie against the developing posterior lobe. This explains why the anterior lobe receives no direct neural innervation from the brain. Subsequently both parts are joined and encapsulated into a single organ, the pituitary gland. Both parts release their contents into the bloodstream.



	The posterior pituitary consists of the pars nervosa and the infundibulum (stalk). The latter is continuous with the median eminence of the hypothalamus. There are no neuronal cell bodies in the pars nervosa (posterior pituitary). The cell bodies are located in the supraoptic and paraventricular nuclei of the hypothalamus. The axons form the hypothalamohypophyseal tract. Their terminals end near fenestrated capillaries and release vasopressin (= antidiuretic hormone = ADH) from the supraoptic nucleus, and oxytocin from the paraventricular nucleus. Oxytocin causes milk letdown during nursing, and uterine contraction during labor. Vasopressin elevates blood pressure, by causing water retention by kidneys, and by causing smooth muscle contraction in arteries. Herring bodies are swellings of these axons and terminals that contain accumulations of neurosecretory granules. Pituicytes, glia that support the neuronal processes, are the only cell type specific to the neurohypophysis.



	The hypophyseal portal system Blood flows through the anterior pituitary via the following route: Internal carotid artery (ICA) Superior hypophyseal arteries (SHA) Capillaries of median eminence and infundibulum (ME) Hypophyseal portal veins (HPV) Capillaries of the hypophyseal portal system in the pars distalis (PD) Hypophyseal veins Note: Capillaries to veins to capillaries.

	The role of releasing factors in initiating hormone release from the anterior pituitary: Fenestrated capillaries perfuse the median eminence of the hypothalamus, at the base of the pituitary stalk. Hypothalamic releasing and inhibiting factors are secreted from neurons into these capillaries and travel via the hypophyseal portal veins to the sinusoidal capillaries of the anterior pituitary. There they act on endocrine cells, causing them to, or inhibiting them from, releasing pituitary hormones into the same capillaries, from which they travel to their appropriate end organs.



	Prolactin (Pro) Leutinizing Hormone (LH) Follicle stimulating hormone (FSH) Thyroid stimulating hormone (TSH = thyrotropin) Adrenocorticotropic hormone (ACTH = corticotropin) Growth hormone (GH = somatotropin). Overproduction of GH during infancy (due to a pituitary tumor) leads to gigantism.



	Chromophils are cells having an affinity for dyes - these are the the main secretory cells of the anterior pituitary. Chromophils are divided into two types: Acidophils are stained by acid dyes, Basophils are stained by basic dyes. The dyes are staining the secretory granules in the cells. The chromophobes are thought to either represent nonspecific stem cells or partially degranulated chromophils.

	Immunocytochemical LM studies have demonstrated that, with few exceptions, each anterior pituitary cell produces just one hormone. Acidophils: Somatotrophs: secrete somatotropin (growth hormone) Mammotrophs (lactotrophs): secrete prolactin Basophils: Corticotrophs: secrete corticotropin (ACTH) Thyrotrophs: secrete thyrotropin (TSH) Gonadotrophs: secrete FSH and LH

	Each specific hormone-secreting cell type also has a distinctive appearance by EM, distinguished primarily on the basis of the size, shape and electron density of the secretory granules.

	The thyroid gland is located in the anterior portion of the neck, just inferior to the larynx. The thyroid synthesizes and releases 3 hormones: From the Follicular cells: T4 (Thyroxine): Regulates cell and tissue metabolism. T3 (Triiodothyronine). Same function as T4. Most circulating T3 is formed in the liver by deiodination of T4. T4 and T3 regulate cell and tissue metabolism. Secretion of T4 and T3 is under the control of TSH secreted by the anterior pituitary. From the Parafollicular cells: Calcitonin. Calcitonin regulates blood calcium levels (more about calcitonin later). The right figure depicts the negative feedback regulation that controls TSH release from the anterior pituitary. This is typical of negative feedback regulation for all anterior pituitary hormones. The general principle is that when the end stage hormone is circulating in elevated concentrations, it binds to receptors in both the hypothalamus and anterior pituitary to reduce the synthesis and release of both the releasing and pituitary hormones controlling its levels.

	The importance of negative feedback in the control of pituitary secretion is revealed in instances where it is disrupted, such as goiter. In the absence of sufficient dietary iodine, T3 and T4 levels decrease, leading to decreased negative feedback control over TSH secretion. This results in increased TSH secretion, leading to abnormal growth of the thyroid gland, but still abnormally low thyroid hormone. Other clinical features of the thyroid gland: Symptoms of hyperthyroidism (e.g., Grave's disease): increased food intake, weight loss, heat intolerance, increased sweating, increased heart rate. Symptoms of hypothyroidism: In infants: cretinism; In adults: weight gain, intolerance of cold, decreased sweating, low cardiac output. Treatment: T4 administration.

	The thyroid gland is surrounded by a dense irregular collagenous connective tissue capsule. Septa derived from the capsule subdivide the gland into lobules. The follicle is the structural unit of the thyroid gland, and is a roughly spheroidal compartment with a wall made of simple squamous to low columnar epithelial secretory cells. The thyroid is unique in that hormone is stored prior to secretion outside the cell, in the thyroid follicles. Secretion involves reabsorption of the hormone by the follicular cells, which then release it into the interstitial spaces, from where it diffuses into the rich capillary network surrounding the follicles. Left figure: LM view. Right figure: scanning electron micrograph view, showing thyroid follicles emptied of colloid.





	Two views of a single thyroid follicle. Left: Opened follicle, emptied of colloid to reveal the follicular secretory cells (EC) and the capillaries (Ca) that make up the walls of each follicle. Right: The external surface of a single follicle, showing the capillary plexus surrounding it.

	This shows LM and EM views of the key components of the thyroid gland. The follicular cells synthesize T3 and T4, which are then stored until needed as thyroglobulin colloid. Sinusoidal capillaries lie between the follicles. Between them are found the parafollicular cells (clear cells), that synthesize calcitonin. Calcitonin secretion is stimulated by high plasma levels of calcium. Calcitonin acts to lower calcium levels by 1) inhibiting bone resorption by osteoclasts and 2) stimulating urinary excretion of calcium and phosphate by inhibiting their reabsorption in the kidneys. Calcitonin is being used clinically to aid patients in reversing osteoporosis.

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