OBJECTIVES

This chapter should help you to:

· Describe the location and embryonic origins of the pituitary.
· Name the divisions of the pituitary.
· Name the cell types found in each division of the pituitary and indicate any characteristic staining properties.
· List the hormones produced by the pituitary. indicating for each the division and cell type rcsponsi ble for its production as well as its target site.
· Describe the role of the hypothalamus in controlling pituitary function.
· Describe the blood supply to the pituitary and its role in pituitary function.
· Explain the role of negative feedback in controlling pituitary function.
· Distinguish between the neurohypophysis and the adenohypophysis and identify the cell types present in a slide or photomicrograph of the pituitary. Also locate and identify the pars anterior, pars tuberalis, pars intermedia, pars nervosa, infundibulum, Rathke's cysts, and the sinusoidal capillaries .

I. GENERAL FEATURES OF THE ENDOCRINE SYSTEM

A. Components of the System: The endocrine system includes several endocrine organs leg, adenohypophysis, thyroid gland, adrenal gland), islands of endocrine tissue in exocrine glands leg, islets of Langerhans), and some isolated endocrine cells leg, cells with DNES functions in the mucosa of the digestive tract).

B. Origin: Endocrine glands are ductless glands that develop as invaginations of epithelial sur faces, such as oral ectoderm or gut endoderm, and eventually pinch off, losing contact with the parent epithelium.

C. Microscopic Structure: Endocrine glands typically contain numerous secretory cells ar ranged as cords, clumps, or hollow folliclcs that are in direct contact with abundant capillaries or sinusoids.

D. Secretions: Endocrine cells release their merocrine secretions-typically hormones--into the bloodstream. Other products that are released into the bloodstream instead of into ducts leg, enzymes, serum albumin), however, are also considered endocrine secretions. Hormones are molecules with specific regulatory effects on a particular target cell, tissue, or organ that is often located at a distance from the gland. Hormones elicit specific and dramatic effects at very low concentrations, and they directly or indirectly affect all tissues; many are essential to maintaining the internal steady-state environment. They regulate carbohydrate, protein, and lipid metab olism; the mineral and water balance in body fluids; growth; sex-related differences in body shape and sexual function; and behavior, temperament, and emotions.

1. Peptide hormones. These proteins, glycoproteins, or short peptides bind to specific recep tors on target cell surfaces. They often stimulate the production of intracellular second messengers, such as cyclic AMP, in the target cells.
2. Steroid hormones. These lipid soluble hormones easily cross the target cells' plasma membranes to directly affect cell function. They bind to specific binding proteins in the cytoplasm and the nucleus. The nuclear receptors bind to the DNA and directly affect gene transcrip tion.

E. Neuroendocrine System: The complex, interrelated functions of cells, tissue, and organs are controlled and coordinated by 2 overlapping systems: the nervous system (discussed in Chapter 9) and the endocrine system (discussed here and in Chapters 21-23). Increasingly, these are considered parts of a single neuroendocrine system. Once called the master gland for its ability to control secretion by other glands, the pitnitary (hypophysis) is now seen more as a focal connection between the endocrine and nervous systems. The secretory activities of its 2 parts, the adenohypophysis and the neurohypophysis, are both controlled by a nearby part of the brain, the hypothalamns. Hypothalamic activity is controlled by neural connections with other parts of the nervous system and by negative feedback from the hormones produced by the pituitary's target cells. Pituitary related diseases present primarily as the effects of hypersecre tion or hyposecretion of pituitary hormones; they may be caused by lesions of the pituitary, its target organs, or the hypothalamus.

II, LOCATION, GENERAL ORGANIZATION, & EMBRYONIC ORIGINS OF THE PITUITARY

The pituitary gland is suspended by a stalk from the hypothalamus at the base of the diencephalon. It rests in a saddlelike depression in the sphenoid bone called the sella turcica, behind the optic chiasm. Its 2 major divisions, the anterior adenohypopbysis and the posterior neurohypopbysis, differ in embryonic origin, structure, and function (Table 20-1).

A. Adenohypophysis:

1. Origin. The adenohypophysis arises as an upward evagination of the cctodcrm lining the primitive oral cavity (Fig 20-1), It contacts and fuses with the neurohypophyseal down- growth .
2. General structure, The adcnohypophysis is composed of cords of glandular epithelial cells separated by the numerous sinusoidal capillaries of the secondary capillary plexus. It is not directly innervated by hypothalamic nerves, but only by autonomic fibers from the carotid plexus.
3. Subdivisions. The pars distalis (pars anterior) is the largest subdivision of the pituitary (Fig 20-2). The pars tuberalis, the superior extension of the pars distalis, forms a partial sleeve around the infundibulum of the neurohypophysis. The pars intermedia is a narrow band of adenohypophyseal tissue that borders the neurohypophysis. These divisions and their functions are discussed in detail in section III.

B. Neurohypophysis:

1. Origin. The neurohypophysis arises as a downgrowth of the neural ectoderm of the hypothalamus and is therefore actually a part of the brain (Fig 20-1).
2. General structure. The neurohypophysis contains abundant axons whose cell bodies are located mainly in the supraoptic and paraventricular nuclei of the hypothalamus.
3. Subdivisions. The infundibulum consists of the infundibular stem (neural stalk) and the median eminence (Fig 20-2). The stem carries axons from the hypothalamus to the pars nervosa and contains the capillary loops of the primary capillary plexus. The median emi nence of the tuber cinereum forms the floor of the hypothalamus. The pars nervosa (infundibular process) is the expanded lobe of the neurohypophysis; it contains axon terminals and numerous capillaries.

III. ADENOHYPOPHYSIS

Each secretory cell in the adcnohypophysis synthesizes and stores one of the following hormones: follicle-stimulating hormone (FSH), thyrotropin (thyroid-stimulating hormone, TSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin. These hormones control the secretory activities of many other glands. Their release is regulated by specific releasing or inhibiting hormones produced by the hypothalamus and delivered to the adenohypophysis by the blood in the hypophyseal portal system (III.D).

A. Pars Distalis:

1. Chromophobes, These cells stain poorly and appear clear or white in tissue sections. Together, the 3 subpopulations of chromophobes make up about 50% of the epithelial cells in the pars anterior. They include (1) the undifferentiated nonsecretory cells, which may be stem cells; (2) the partly degranulated chromophils, which contain sparse granules; and (3) the follicular cells, the predominant chromophobe type, which form a stromal network that supports the chromophils. These stellate cells may have some phagocytic functions.
2. Chromophils, These hormone-secreting cells of the adenohypophysis stain intensely owing to their abundant cytoplasmic secretory granules in which their hormones are stored. There is a specific cell type for each hormone. Usually larger than chromophobes, chromophils are subdivided into 2 classes: a. Acidophils. These cells secrete simple proteins. They stain intensely with eosin and orange G, but not with PAS. More abundant in the periphery of the gland, they are usually smaller than basophils and their granules are larger and more numerous. The acidophils include 2 major types of hormone-secreting cells: somatotropes, which produce growth hormone (GH, somatotropin), and mammotropes, which produce pro lactin, (A simple mnemonic device for remembering the hormones secreted by acid ophils is GPA--growth hormone, prolactin, acidophils.) b. Basophils, These cells, which stain with hematoxylin and other basic dyes, secrete glycoproteins and are PAS-positive. More abundant in the core of the gland, they are usually larger than acidophils, with fewer and smaller granules. The 3 major types of hormone-producing basophils produce 4 major hormones. (A mnemonic for the hor mones produced by basophils is B-FLAT-Basophils, FSH, LH, ACTH, TSH.) (1) Each of the 2 types of gonadotropes produces a different gonadotropin. One pro duces follicle-stimulating hormone (FSH); the other produces luteinizing hor- mone (LH; called interstitial cell-stimulating hormone [ICSH] in males). (2) Corticotropes produce adrenocorticotropin (ACTH). (3) Thyrotropes produce thyrotropin (thyroid-stimulating hormone, TSH),

B. Pars Tuberalis: This funnel-shaped superior extension of the pars distalis surrounds the infundibular stem (Fig 20-2). Its histology is similar to the pars distalis, but it contains mostly gonadotropes. The pars tuberalis contains many capillaries of the primary capillary plexus of the hypophyseal portal system.

C. Pars Intermedia: This is a band or wedge of adenohypophysis between the pars distalis and pars nervosa; it is rudimentary in humans. It contains Rathke's cysts, small, irregular, colloid containing cavities lined with cuboidal epithelium that are the remnants of Rathke's pouch. It also contains scattered clumps and cords of basophilic cells, or melanotropes, which secrete melanocyte-stimulating hormone (P-MSH).

D. Blood Supply and Hypophyseal Portal System:

1. Primary capillary plexus. This profusion of capillaries lies in the upper infundibular stalk and lower median eminence; it extends into the pars tuberalis (Fig 20-2). The plexus receives blood from the anterior and posterior superior hypophyseal arteries (from the circle of Willis) and drains into the hypophyseal portal veins.
2. Hypophyseal portal veins. These small veins and venules lie mainly in the middle and lower infundibular stalk and in portions of the pars tuberalis. They receive blood from the primary capillary plexus and carry it directly to the secondary capillary plexus in the pars distalis (Fig 20-2). Vessels carrying blood directly from one capillary plexus to another without returning to the general circulation are defined as portal vessels.
3. Secondary capillary plexus. This rich fenestrated capillary plexus located throughout the pars distalis also penetrates the pars tuberalis and pars intermedia (Fig 20-2). There are also some connections between this capillary bed and that in the pars nervosa. The capillaries between the clumps and cords of cells in the pars distalis belong to this plexus, which receives venous blood directly from the hypophyscal portal veins and arterial blood from the anterior inferior hypophyseal arteries. It is drained by the inferior hypophyseal veins into the internal jugulars.

E. Hypothalamic Releasing and Inhibiting Hormones: These small peptides are synthe sized in the neuron (neurosecretory) cell bodies in the hypothalamic nuclei and are released by their axon terminals into the primary capillary plexus. They pass through the hypophyseal portal venules and into the secondary capillary plexus, from which they diffuse into the adenohypophysis to stimulate or inhibit the release of hormones by the acidophiis and basophils.

1. Releasing hormones. Corticotropin-releasing hormone (CRH) is a 41-amino-acid peptide synthesized in the paraventricular nucleus; it stimulates corticotropes to release ACTH. Gonadotropin-releasing hormone (GnRH), a l0-amino-acid peptide synthesized in the preoptic and arcuate nuclei, stimulates gonadotropes to release FSH and LH. Thyrotropin releasing hormone (TRH) is a 3-amino-acid peptide that stimulates thyrotropes to release TSH (thyrotropin).
2. Inhibiting hormones. Somatostatin (GHIH [growth hormone-inhibiting hormonel) is a 14 amino-acid peptide synthesized in the suprachiasmatic nuclei that inhibits somatotropes from releasing growth hormone (GH, somatotropin). It also inhibits the secretion of glucagon, insulin, and other hormones associated with the gastrointestinal tract. Dopamine (a prolactin-inhibiting hormone [PIHI), is a neurotransmitter synthesized in the arcuate nuclei that inhibits mammotropes from releasing prolactin.

F. Summary of Adenohypophyseal Hormone Production:

1. Neurons of the hypothalamic nuclei synthesize releasing or inhibiting hormones and package them in neurosecretory vesicles.
2. The neurons transport the vesicles down axons in the tuberoinfundibular and hypo thalamohypophyseal tracts to collect in the axon terminals that surround the capillaries of the primary plexus.
3. Neural stimulation or hormonal feedback from the target organs of the adenohypophysis causes these nerves to fire an action potential that releases the appropriate releasing or inhibiting hormone from the axon terminals.
4. The releasing or inhibiting hormone then enters the primary capillary plexus and flows through the hypophyseal portal veins to the secondary capillary plexus.
5. There, the hormone diffuses out of the capillary lumen via the fenestrae and stimulates or inhibits the release of stored adenohypophyseal hormones from the acidophils or basophils. 6. The adenohypophyseal hormones enter the capillaries of the secondary plexus; they leave the adenohypophysis through the anterior inferior hypophyseal veins to enter the general circulation.

IV. NEUROHYPOPHYSIS

The subdivisions of the neurohypophysis (outlined in II.B.3) all exhibit similar microscopic structure. For the sake of brevity, the pars nervosa is used here to represent the neurohypophysis. The neurohypophysis has 3 major structural components: axons, capillaries, and pituicytes.

A. Axons of Neurosecretory Cells: The neurohypophysis stains poorly if at all. It contains many unmyelinated axons whose cell bodies (soma) are located mainly in the supraoptic and paraventricular nuclei (Fig 20-2) of the hypothalamus. Axons passing from these nuclei to the pars nervosa are together termed the hypothalamohypophyseal tract. The axons contain neu rosecretory granules and exhibit large granule-filled dilations called Herring bodies. The neu rosecretory materials in these granules, synthesized and packaged in the above-mentioned cell bodies, include the following products:

1. Neurohypophyseal hormones. The hypothalamic neurons that terminate in the neu rohypophysis release oxytocin and antidiuretic hormone around the capillaries in this part of the pituitary. Oxytocin is a 9-amino-acid peptide synthesized mainly by cells of the para ventricular nucleus. It stimulates milk ejection by the mammary glands and stimulates the contraction of uterine smooth muscle during copulation and childbirth. Antidiuretic bor mone (ADH, arginine vasopressin) is a 9-amino-acid peptide synthesized mainly by cells in the supraoptic nucleus. It stimulates water resorption by the renal medullary collecting ducts (see Chapter 19) and contraction of vascular smooth muscle.
2. Neurophysin is a binding protein that complexes with neurohypophyseal hormones.
3. ATP (adenosine triphosphate) acts as a source of chemical energy for the neurosecretory process.

B. Fenestrated Capillary Plexus: Surrounding the axon terminals in the pars nervosa, these capillaries pick up the neurosecretory products and convey them to the general circulation.

C. Pituicytes: These are highly branched glial cells whose processes surround and support the unmyelinated axons.

D. Summary of Neurohypophyseal Hormone Production: Neurons of the supraoptic and paraventricular nuclei of the hypothalamus synthesize ADH and oxytocin, respectively. The neurons package these hormones with neurophysin and ATP in neurosecretory vesicles. The vesicles are transported by the neurons down axons in the hypothalamohypophyseal tract to axon terminals among the capillaries of the pars nervosa. Upon appropriate stimulation, these neurosecretory cells propagate an action potential along their axons, causing exocytosis of the vesicle contents at the axon terminals. The released hormones enter the capillaries of the pars nervosa and leave the pituitary to enter the general circulation via the posterior inferior hypo physeal veins.

 Endocrine Glands- Adrenals etc...

OBJECTIVES

This chapter should help you to:

· Describe the structure, function, and location of the islets of Langerhans, the pineal body, and the adrenal, thyroid, and parathyroid glands.
· Describe the embryonic origin of the adrenal cortex and medulla and the thyroid and parathyroid glands.
· Describe the innervation and blood supply to the adrenal glands, islets of Langerhans, thyroid gland, and pineal body.
· Name the hormones produced by the adrenal cortex and medulla, islets of Langerhans, thyroid and parathyroid glands, and pineal body; for each hormone produced, identify the cell type responsible for its secretion, neural and endocrine factors that regulate its production, and the main target cells and effects.
· Compare the 3 layers of the adrenal cortex in terms of histologic structure, hormones secreted, and location; describe the fetal (provisional) cortex. · Identify the capsule, cortex, zona glornerulosa, zona fasciculata, zona reticularis, medulla, chromaftin cells, and ganglion cells in a slide or photomicrograph of a section of the adrenal gland. · Identif-i the islets of Langerhans in a slide or photomicrograph of a section of the pancreas.
· Trace the steps in the synthesis, storage, and secretion of the hormones produced by the thyroid follicular cells, referring to the specific organelles and compartments that take part in the process.
· Identify the thyroid follicles, follicular cells, basement membrane, colloid, capillaries, and para follicular cells in a slide or photomicrograph of a section of the thyroid gland; distinguish between an active and inactive thyroid gland on the basis of follicular morphology.
· Compare parathyroid chief and oxyphil cells in terms of their relative number and histologic appearance.
· Identify the capsule, chief cells, and oxyphil cells in a slide or photomicrograph of a parathyroid gland section.
· Compare pinealocytes and astroglial cells in terms of their histologic appearance and distribution in the pineal body. · Describe the histologic appearance, composition, and age-related changes of the corpora arenacea (brain sand).
· Identify the pinealocytes, astroglial cells, and brain sand in a slide or photomicrograph of the pineal gland.

SYNOPSIS

I. GENERAL FEATURES OF ENDOCRINE SECRETORY CELLS: STRUCTURE-FUNCTION RELATIONSHIPS

Knowledge of a hormone's structure allows the prediction of the ultrastructure of the secretory cell that produces it. For example, cells that secrete steroid hormones contain abundant SER, whereas those that secrete peptide hormones contain abundant RER. (Other general features of the structure and function of endocrine glands are described in Chapter 20.)

II. ADRENAL (SUPRARENAL) GLANDS

Forming a cap over each kidney, these can be divided by embryonic origin, structure, and function into cortex and medulla.

A. Adrenal Cortex:

1.Embryonic origin. The adrenal cortex derives from coelomic intermediate mesodcrm.
2. Structure in adults. Cells of the adrenal cortex have the characteristic structure of steroid synthesizing cells (see Chapter 4). The cortex has 3 layers, the zonae glomerulosa, fas ciculata, and reticularis. a. Zona glomerulosa, The outermost cortical layer, it lies directly beneath the capsule and constitutes 15% of adrenal volume. Its cells form arched clusters (glomeruli) surrounded by capillaries. The secretory cells of this layer produce mineralocorticoids, b. Zona fasciculata, The middle layer of the adrenal cortex, it constitutes 65% of adrenal volume. Its cells form straight cords (fascicles) that run perpendicular to the organ surface. The cells in this layer produce glucocorticoids and some adrenal androgens upon appropriate stimulation. c. Zona reticularis. This is the innermost layer of the adrenal cortex and constitutes 7% of adrenal volume. Its cells are arranged in irregular cords that form an anastomotic network (reticulum). Its cells resemble those in the fasciculata but are smaller and more acid ophilic. They contain fewer lipid droplets, more mitochondria, and numerous lipofuscin granules. The reticularis and fasciculata appear to constitute a single functional zone, with the reticularis producing most of the glucocorticoids and adrenal androgens and the fasciculata representing a reserve zone activated by prolonged stimulation.
3. Normal function, The adrenal cortex produces 3 types of steroid hormones. a. Mineralocorticoids, Consisting mainly of aldosterone, these are produced by the zona glomerulosa in response to stimulation, primarily by angiotensin II but also to a lesser extent by ACTH. Aldosterone controls water and electrolyte balance mainly by stimulat ing sodium absorption by the distal renal tubules but also by affecting the gastric mucosa and salivary glands. b. Glucocorticoids. Mainly cortisol and corticosterone, these are produced by the zona reticularis in response to ACTH and by the fasciculata after prolonged stimulation. Glucocorticoids control carbohydrate metabolism, especially by stimulating carbohy drate synthesis in the liver. They have the opposite effect in other tissues that catabolize (degrade) carbohydrates to provide raw material for the liver. Glucocorticoids also sup press the immune response by decreasing the number of circulating lymphocytes and eosinophils. c. Adrenal androgens, These androgens, mainly dehydroepiandrosterone, are secreted in response to ACTH by the zona reticularis and, after prolonged stimulation, by the fasciculata. The masculinizing and anabolic effects of adrenal androgens are similar to those of testosterone but less potent.
4. Abnormal function a. Hypersecretion. Gushing's syndrome is caused by the hypersecretion of cortisol and often of androgens. Its symptoms include truncal obesity, a round "moon face," high blood sugar, diabetes mellitus, hirsutism, amenorrhea, acne, and emotional lability. Hypersecretion of aldosterone (Conn's syndrome, for example) causes sodium and water retention, increasing the blood pressure (hypertension). b. Hyposecretion, Chronic hypofunction of the adrenal cortex leg, Addison's disease) causes low levels of serum glucose, sodium, chloride, and bicarbonate and high levels of serum potassium. It results in weakness, nausea, weight loss, and elevated ACTH levels (the last causing hyperpigmentation). Without testicular androgens to compensate, decreased adrenal androgen synthesis in women may cause the loss of pubic and axillary hair.
5. Fetal, or provisional, cortex. The thickest adrenal layer before birth, it is located between the medulla and the immature thin permanent cortex. It produces sulfated androgens that are activated by the placenta and enter the maternal circulation. After birth, the fetal cortex regresses and the permanent cortex develops the 3 layers described above.

B. Adrenal Medulla:

1. Embryonic origin. The adrenal medulla derives from the neural crest. 2. Structure. It contains 2 major cell types: chromaffin and ganglion cells. a. Chromaffin cells. Also known as pheochromocytes, these constitute the predominant medullary cell type; they are modified postganglionic sympathetic neurons that have lost their axons and dendrites. They contain large nuclei, abundant electron-dense secretory granules filled with catecholamines (epinephrine or norepinephrine), a well-developed Golgi complex, a few profiles of RER, and many oval mitochondria. Their secretory granules have a strong affinity for chromium-containing stains. Chromaffin cells synthc size and release their catecholamines upon neural stimulation, especially stress, mediated by preganglionic sympathetic neurons. b. Ganglion cells, The few parasympathetic ganglion cells present exhibit typical mor- phological characteristics of autonomic ganglion cells (see Chapter 9).
3. Normal function. These include the production of 2 types of catecholamines-epinephrine and norepinephrine--in response to preganglionic sympathetic stimulation leg, stress). Both elevate blood glucose by stimulating glycogenolysis in the liver; they also increase blood Bow to the heart. a. Epinephrine increases heart rate and dilates blood vessels to the organs needed to combat or escape stress, such as cardiac and skeletal muscle. It dilates bronchioles and constricts vessels in organs leg, skin, digestive tract, kidneys) that are not essential in reacting to stress. b. Norepinephrine constricts blood vessels in nonessential organs. By increasing pe ripheral resistance, it increases blood pressure and blood flow to the heart, brain, and skeletal muscle.
4. Abnormal function, Hypcrsccrcting chromaffin cell tumors (pheochromocytomas) cause a sustained stress response (especially hypertension) even in the absence of stress. Ganglion cell tumors (neuroblastomas and ganglioneuromas) are more common, especially in chil dren, but their clinical manifestations vary.

C. Adrenal Blood Supply:

1. Arteries. Three main arteries supply each adrcnal gland: the superior suprarenal from the inferior phrenic artery, the middle suprarenal from the aorta, and the inferior suprarenal from the renal artery. They penetrate the capsule separately, and their branches anastomose to form a subcapsular arterial plexus. This plexus gives rise to 3 groups of arteries: the arteries of the capsule; the arteries of the cortex, which branch to form the cortical capil laries that pass between the secretory cells and drain into the medullary capillaries; and the arteries of the medulla, which traverse the cortex without branching until they reach the medulla, where they form the medullary capillaries.
2, Medullary capillaries receive a double blood supply from arteries of both the cortex and medulla and converge to form several medullary veins.
3. Medullary veins converge to form a single large suprarenal vein.
4. The suprarenal vein lies at the core of the medulla and drains into the renal vein or directly into the inferior vena cava.

III. ISLETS OF LANGERHANS

These small nests of endocrine cells distributed throughout the pancreas contain 4 major peptide hormone-secreting endocrine cell types:

A.   A Cells (Alpha Cells): In response to low blood glucose, these cells secrete glucagon, whose effects are opposite to those produced by insulin.

B.   B Cells (Beta Cells): The most numerous cell type in the islcts, these cells secrete insulin in response to high blood glucose. Before its release, insulin is stored, complexed with zinc, in cytoplasmic granules. Insulin enhances glucose uptake by most cells, glycogen synthesis by hepatocytes, and triglyceride synthesis by adipocytes. B cell malfunction causes diabetes mellitus, a condition manifested by a great excess of blood glucose (byperglycemia) that spills over into the urine (glycosuria), Hypcrplasia and neoplasia of the B cells may result in hyperin sulinism syndrome, characterized by hypoglycemia,

C.   D Cells (Delta Cells): Somatostatin, which suppresses the release of insulin, glucagon, and growth hormone, is secreted by these cells. They may also secrete gastrin, which stimulates secretion by glands in the gastric mucosa. Zollinger-Ellison syndrome (gastrinoma) causes peptic ulcers through excessive acid secretion by parietal cells in the gastric mucosa. Somatostatinomas are rare tumors with complex effects

D.   F Cells (PP Cells): These cells secrete pancreatic polypeptide, which inhibits pancreatic exocrine secretion of enzymes and bicarbonate. It also causes relaxation of the gallbladder and decreases the secretion of bile.

IV. THYROID GLAND

During week 4 of fetal development, the thyroid arises as an outpocketing of the endoderm lining the Hoor of the embryonic pharynx; it soon divides in two. In adults the thyroid lies anterior to the larynx and has 2 lobes connected by an isthmus. Each lobe consists of numerous spheric follicles and is covered by a thin capsule that penetrates the parenchyma to form septa.

A. Thyroid Follicles: Each follicle consists of an outer simple epithelium of follicular cells enclosing a central lumen filled with colloid (Fig 21-1). The follicles, which vary in size, enlarge during stimulation.

B. Thyroid Follicular Cells:

1.Structure, Thyroid follicular cells, which derive from endoderm, exhibit a typical peptide hormone-secreting cell ultrastructure. The cell height ranges from squamous in inactive glands to columnar during stimulation.
2. Normal function, Thyroid follicular cells differ from other endocrine cells in that they store an intermediate form of their secretory product (thyroglobulin) extracellularly in colloid rather than internally in cytoplasmic granules. Stimulation by pituitary TSH (see Chapter 20), which generally follows an increased demand for energy, increases synthesis and secrc tion. . a. Synthesis and storage of thyroglobulin. The steps required by this process (Fig. 21-2) are (i) synthesis of the tyrosine-rich protein, thyroglobulin, on the RER; (2) glycosyla tion of the protein in the ER and Golgi complex; (3) packaging in vesicles in the Golgi complex; and (4) fusion of the vesicles with the apical cell membrane, resulting in exocytosis of the thyroglobulin into the colloid in the lumen of the folliclc. b. Uptake and oxidation of iodide, A molecular pump in the follicular cell's basal plasma membrane transfers circulating iodide into the cytoplasm. It is oxidized by peroxidase and then transferred to the cell's apex. Iodide uptake is also stimulated by TSH. c. Iodination of thyroglobulin and formation of thyroid hormone. Enzymes in the plasma membranes of the apical microvilli projecting into colloid catalyze the iodination of tyrosine residues in the thyroglobulin, a reaction that occurs at the microvillus-colloid interface. One iodide molecule is added to tyrosine, forming monoiodotyrosine (MIT). A second iodide molecule is then added to some tyrosine residues, forming di-iodotyrosine (DIT). Coupling of the 2 iodinated tyrosines forms a thyronine molecule. Coupling 2 DIT molecules forms tetraiodothyronine (thyroxine; T,), while coupling 1 MIT and 1 DIT forms triiodothyronine (T,), Although T, makes up 90% of the thyroid hormone produced, it is not as potent as the less common T,. d. Thyroid hormone secretion. Stimulation by TSH causes the follicular cells to pi nocytose portions of the colloid, forming vesicles that contain iodinated thyroglobulin. These vesicles fuse with lysosomes containing enzymes that cleave the thyroglobulin. The T, and T, released in this way diffuse out of the secondary lysosomes (see Chapter 3). They pass through the cytoplasm and cross the basolateral plasma membranes to reach the bloodstream. e. Targets and effects of thyroid hormones. T, and T, act on cells throughout the body to increase their basal metabolic rate tie, the rate at which cells use glucose), promote cell growth, increase heart rate, raise body temperature, and generally enhance all energy requiring cell functions. They also act on the TRH-secreting cells of the hypothalamus and the thyrotropes in the adenohypophysis to reduce TSH secretion (negative feed back).
3. Abnormal Function a. Hyperthyroidism. The overproduction of thyroid hormone (thyrotoxicosis) causes ner vousness, palpitation, rapid pulse, muscular weakness, fatigue, weight loss with good appetite, excessive perspiration, intolerance of heat, and emotional lability. Hyperactive thyroid follicles that enlarge because of the increased height of the follicular epithelium and increased deposits of thyroglobulin cause a swelling of the thyroid gland known as goiter. b. Hypothyroidism, Termed cretinism in children and myxedema in adults, hypothyroid ism causes poor glucose utilization. Its symptoms include lethargy, intolerance of cold, slowing of intellectual and motor skills, accumulation of glycosaminoglycans in the dermis (with consequent bloating), and sometimes weight gain. Since iodine is required for normal thyroid function, iodine-dcficicnt diets reduce functional thyroxine production and often underlie cretinism and myxedema. Because uniodinated thyroxine caused by iodine deficiency cannot provide negative feedback on TSH production, follicular en largement and goiter may accompany this type of hypothyroidism.

C.  Parafollicular Cells (C Cells): These are found in the thyroid gland, interspersed among the follicular cells or in clusters between the follicles (Fig 21-1). In humans, parafollicular cell cytoplasm stains poorly with standard stains and typically appears clear or white. Electron micrographs reveal numerous small secretory granules. C cells secrete the peptide hormone calcitonin in response to high blood calcium. Calcitonin causes calcium uptake by cells and increased calcium deposition in bone, lowering blood calcium levels.

V. PARATHYROID GLANDS

These 4 small glands, located on the posterior surface of the thyroid gland, derive from the third and fourth pharyngeal pouches (endoderm). In adults, they are composed of 2 major parenchymal cell types, chief and oxyphil cells (which may be different forms of the same cell type).

A. Chief Cells: These are the most numerous of the parenchymal cells.

1. Structure. These small (4-8 CLm in diameter) polygonal cells exhibit typical peptide secrc tory cell ultrastructure; they contain abundant small secretory granules in their pale-staining cytoplasm.
2. Normal function. Chief cells secrete parathyroid hormone (PTH) in response to low blood calcium levels. PTH, a peptide hormone, increases blood calcium levels by acting at 3 target sites. In bone, PTH increases bone resorption. In the kidneys, it increases phosphate excretion and calcium reabsorption and causes activation of a vitamin D precursor. In the intestines, PTH (perhaps by activating vitamin D) causes increased absorption of calcium from food by the intestinal mucosa. Increased blood calcium Ievels decrease PTH secretion.
3. Abnormal function a. Hyperparathyroidism. Excessive PTH secretion elevates serum calcium (hyper calcemia) and decreases serum phosphate (hypophosphatemia). Its effects include in creased urine calcium, abnormal calcium deposits in the arteries and kidneys, and exces sive loss of calcium from bones, resulting in osteomalacia and osteitis fibrosa cystica. b, Hypoparathyroidism. Insufficient PTH secretion disrupts neuromuscular function. The resulting low blood calcium level leads to spontaneous and uncontrolled firing of action potentials. In peripheral nerves this may cause spastic muscle contraction, or tetany, The spontaneous firing of neurons in the brain may cause behavioral effects as well.

B. Oxyphil Cells: These are larger and less numerous than chief cells; their content of mitochondria makes them intensely acidophilic. Oxyphil function is not clearly understood.

VI, PINEAL BODY

This small (3-5 mm x 5-8 mm), conical organ (the epiphysis cerebri) attaches by a stalk to the roof of the diencephalon near the postcrior aspect of the third ventricle. Its pia mater covering penetrates the organ, carrying blood vessels and forming irregular septa. The pineal contains clusters of globular, basophilic, calcified matrix known as brain sand (corpora arenacea), which increase in size, number, and calcification with age. The radioopacity of these bodies, together with the pineal's central location in the skull, makes this organ a useful landmark for radiologists. Its 2 major cell types are pinealocytes and astroglial cells.

A. Pinealocytes:

1. Structure. These cells have large irregular nuclei with prominent nucleoli and pale basophilic cytoplasm. With the del Rio-Hortega silver stain, they exhibit long cytoplasmic processes that terminate as swellings in the septa near blood vessels. The role of pineal innervation (both sympathetic and through the stalk from the posterior commissure) is uncertain.
2. Normal function. Pincalocytes secrete the indoleamine melatonin. Cyclic changes in plasma melatonin levels follow changes in environmental lighting, but the precise relation ship is still unknown. Melatonin may both help establish circadian rhythms and have anti gonadotropic effects that delay onset of sexual maturity until puberty. Other pineal secretions include arginine vasotocin and possibly additional substances that exert an antigonadotropic effect through the hypothalamohypophyseal axis.
3. Abnormal function. Pineal lesions occur most often in young males and may cause either precocious or delayed sexual maturity. Because of their location, pineal tumors may restrict the flow of cerebrospinal fluid through the adqueduct of Sylvius, causing hydrocephalus.

B.  AstroglialCells: Also known as interstitial cells, these glialike cells have elongated hetero chromatic nuclei and long cytoplasmic processes that contain intermediate filaments. They are found around blood vessels and between clusters of pinealocytes.

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