I. Definitions -
Hormones are substances that regulate the activity of cells bearing receptors for the hormone either on their surface or in their cytoplasm. Hormones are carried by the blood stream from their cells of origin to the target cells. They can be derivatives of amino acids ( for example, triiodothyronine, epinephrine), polypeptides (for example, calcitonin, oxytocin), proteins or glycoproteins (for example, thyroid stimulating hormone) or steroids (for example, cortisol, testosterone).
Paracrine (acting on neighboring cells) and autocrine (acting on the cell of origin) secretions also regulate cells via their receptors. However, since they do not depend upon the circulation to find their target cells these are not generally called hormones nor are their cells of origin included in the classical system of endocrine organs.
II. Morphology of endocrine organs -
Endocrine organs are composed of epithelial cells that produce hormones. Epithelial cells are organized in small clumps, irregular cords, irregular plates, or follicles surrounded by basal lamina and closely associated with numerous fenestrated capillaries. There are no ducts. Some hormones are produced by isolated cells within a surface epithelium - the diffuse neuroendocrine system.
PITUITARY GLAND
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1. Adenohypophysis (Adeno = gland) 2. Neurohypophysis (nerve endings secreting hormone) 3. Median eminence (nerve fibers and nerve cell bodies) 4. Infundibular recess of third ventricle 5. Infundibulum or stalk of pituitary gland (nerve fibers) |
I. LOCATION AND SUBDIVISIONS
A. In sella turcica roofed over by diaphragma sella
1. Adenohypophysis from Rathke's pouch (oral ectoderm)
a. Pars anterior (distalis)
b. Pars tuberalis (suprasellar portion)
c. Pars intermedia
2. Neurohypophysis (from diencephalon)
a. Pars nervosa (pars posterior, infundibular process)
b. Infundibulum (neural stalk)
(1) Median eminence (part of tuber cinereum)
(2) Infundibular stalk (partly encircled by pars tuberalis)
II. DEVELOPMENT
A. Rathke's pouch from oral ectoderm forms vesicle anterior to infundibular process. Anterior wall of vesicle proliferates more than posterior wall. Anterior becomes pars distalis; posterior wall becomes pars intermedia. Upward extension becomes pars tuberalis.
B. Pars nervosa formed by nerve fibers from hypothalamus.
III. HISTOLOGY
A. General appearance
1. Pars distalis (anterior) - very cellular; large (acidophils and basophils) and small (chromophobes) in clumps and cords between venous sinusoids. Supported by reticular connective tissue.
2. Pars intermedia - many small cells (nuclei close together) sometimes form colloid filled follicles, their function in the human is not clear but may be related to corticotrophs.
3. Pars nervosa - nonmyelinated nerve fibers in relation to capillaries and supported by modified glial cells (pituicytes) not connective tissue.
1. Chromophobes - 50% - small cells; poorly stained cytoplasm; nuclei close together. there are two types.
a. Resting or discharged chromophils - occasional secretion granules are present.
b. Folliculostellate cells identified with immuno stain for S-100 protein. May serve in paracrine regulation of other cells.
2. Chromophils - 50% - empirical stains divide these into acidophils and basophils, but they all have secretion granules that can be stained differentially using antibodies to specific hormones. When this is done the cells can be named for the specific hormone(s) (mostly glycoproteins) that they produce and store.
a. Acidophils - 35-40%
(1) Somatotrophs - produce somatotrophic hormone (STH).
Release of this growth hormone is stimulated by growth hormone-releasing hormone (GHRH) and inhibited by somatostatin from the hypothalamus.
Target tissues are bone, viscera and soft tissues. In the liver it stimulates the production of somatomedins, insulin-like growth factors I & II, which, in the child, stimulate growth of the epiphyseal disk cartilage.
(2) Mammotrophs (lactotrophs) - These prolactin-producing cells have the largest secretion granules, during pregnancy and lactation (600 nm); at other times the granules are small.
Prolactin's best known target tissues are uterus and mammary glands but recently it has been found to have diverse influences on cells and the nervous system.
Prolactin releasing hormone and oxytocin stimulate secretion. Its release is inhibited by dopamine from the hypothalamus. Decreased dopamine delivery to the pars distalis increases prolactin secretion.
b. Basophils - 10-15%. Three cell types - 4 hormones.
Produce a prohormone peptide ( Pro-opiomelanocortin (POMC))that can be split to give adrenocorticotrophic hormone (ACTH) and beta-lipotrophic hormone (one of three lipolytic hormones from the pituitary gland).
ACTH stimulates the production of glucocorticoids by the adrenal gland.
Beta-lipotrophic hormone has a lipolytic effect but it can be split again to give endorphins and melanocyte stimulating hormone(MSH).
Corticotropic-releasing hormone(CRH) from the hypothalamus stimulates release of these hormones from corticotrophs in the pars distalis.
In the pars intermedia cells stimulated by dopamine process POMC to secrete MSH and several lipolytic peptides
(2) Thyrotrophs - In the pars distalis they have the smallest secretion granules, 140 nm.
They produce thyroid stimulating hormone (TSH) when stimulated by TRH (thyrotropin-releasing hormone). They are inhibited by somatostatin.
(3) Gonadotrophs - produce two hormones.
Luteinizing hormone (LH) - In the male the hormone is called interstitial cell stimulating hormone (ICSH). In both genders this hormone stimulates the production of sex steroids.
Follicle stimulating hormone (FSH) - Functions in both genders to stimulate the formation of gametes.
Stimulation of the release of these hormones is by GnRH (gonadotropic-releasing hormone) from the hypothalamus. They act on the gonads to stimulate production of the gametes and the sex hormones. The gonads in turn release inhibins that inhibit gonadotrophs.
Gonadotrophs are the predominant cell type in the pars tuberalis.
A. Direct - superior and inferior hypophyseal arteries supply parts of both adenohypophysis and neurohypophysis although the pars distalis probably does not receive a direct arterial supply.
B. Indirect - superior hypophyseal arteries to capillaries in neural stalk where they receive neurosecretions (releasing and inhibiting factors) from axons of cells located in the tuberal nuclei. These capillaries drain into hypophyseal portal veins that pass around and through the pars tuberalis to the highly fenestrated sinuses of the adenohypophysis to control release of its hormones. Venous drainage is primarily to the cavernous sinus, but under some circumstances it may flow backward in infundibulum so that adenohypophyseal hormones can go directly to the hypothalamus.
V. NEUROSECRETIONS
A. Releasing (or retaining) factors
1. Tuberal nuclei - controlled by circulating hormones from target glands such as the adrenal cortex, as well as neural circuits of the hypothalamus. Secretions are produced in the soma and transported to axon terminal in the infundibular stalk. Nuclei located in tuber cinereum. At least 2 hormones have both releasing and retaining factors, prolactin and somatotropin.
Vasopressin (antidiuretic hormone, ADH) and oxytocin are polypeptides produced and packaged in the soma of nerve cells in the supraoptic and paraventricular hypothalamic nuclei.
Membrane limited granules containing hormone and a carrier protein, neurophysin(derived from the prohormone), are transported down axons (anterograde transport) of hypothalamo-hypophyseal tract to accumulate in axon terminals of pars nervosa. Some axon terminals are enlarged with secretion granules and myelin type membranous whorls, these are Herring bodies. Nerve fibers end in relation to fenestrated capillaries and are supported by modified glial cells known primarily as pituicytes.
ADH causes conservation of water and concentration of urine, primarily by increasing the permeability of distal convoluted tubules and collecting ducts to water. It is called vasopressin because of its capacity to cause constriction of vascular smooth muscle at high concentrations. That is probably not an important function.
The osmolarity of blood perfusing the supraoptic and paraventricular nuclei controls the release of ADH. There are also neural regulatory circuits arising from the carotid sinuses that detect changes in blood pressure.
Diabetes insipidus (large volumes of dilute urine without sugar) results from anything that prevents ADH secretion.
Oxytocin causes contraction of the uterine smooth muscle and of myoepithelial cells in the mammary glands.
Neural circuits regulate the release of oxytocin. The afferents arise from the stimulation of the nipple in suckling and stretching of the cervix and vagina in preparation for parturition.
THYROID AND PARATHYROID HISTOLOGY
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1. Follicular epithelium 2. Colloid 3. Thyroid follicle 4. Capillaries in C.T. |
A. Triiodothyronine (T3) and tetraiodothyronine(T4) (thyroxine) are unique amino acids produced by the thyroid follicular cells in the proportion 1:20.
They are carried in the blood by thyroxine binding protein and in the tissues T4 is converted to T3. They are metabolic stimulants, T3 being more active than T4. They cause an increase in mitochondria and their content of cristae.
B. Parathormone (PTH) produced by the parathyroid parenchyma is a small polypeptide that elevates blood calcium by acting on the kidney, intestine and bone.
In the kidney it stimulates the formation of the active form of vitamin D. This active vitamin D enhances calcium absorption in the intestines and in bone participates with PTH to stimulate osteoclastic activity.
Bone stromal cells (osteoblasts and their precursors) respond to PTH by secreting an osteoclast-stimulating factor.
C. Calcitonin is a small peptide produced by "C" cells of neural crest origin that decreases blood calcium by inhibiting osteoclastic activity.
II. EMBRYOLOGY
A. Thyroid gland is derived from endoderm that forms the median ventral thyroglossal duct.
B. Superior parathyroid is derived from the endoderm that lines the dorsal aspect of 4th pharyngeal pouch.
C. Inferior parathyroid is derived from the endoderm that lines the dorsal aspect of 3rd pharyngeal pouch. It migrates with the thymus and this accounts for its inferior location.
D. The stroma of the thymus is from the endoderm of the ventral aspect of 3rd pharyngeal pouch and doubtfully a small amount from 4th pharyngeal pouch.
E. Ultimobranchial cells from the endoderm of the 4th pharyngeal pouch migrate with superior parathyroid to fuse with the thyroid. These endodermal cells bring with them cells of neural crest origin that become the C cells.
III. THYROID PARENCHYMA -
This gland consists of simple epithelial follicles 50-500 microns in diameter. Very vascular stroma divides gland into incomplete lobules. Epithelial cells are cuboidal to columnar depending on their activity. They synthesize, store (as colloid), and break down the iodinated tyrosine-rich glycoprotein, thyroglobulin. Rough endoplasmic reticulum, Golgi apparatus and cell apex are involved sequentially in peptide synthesis, carbohydrate addition and iodination.
Mannose is added in ER and galactose in Golgi regions. At the cell apex just before or after the thyroglobulin precursor is released iodination and tyrosine rearrangements occur. This is dependent upon the oxidation of iodide to free iodine by a peroxidase.
Proteolysis (intracellular) of colloid is required for release of hormones through the epithelium into blood and lymph capillaries. Iodine is reclaimed from iodotyrosines by the enzyme dehalogenase. TSH enhances thyroglobulin synthesis and breakdown also hypertrophy and proliferation of follicular epithelium. Thyroid hormones inhibit release of TSH from the pituitary gland.
B. PARAFOLLICULAR CELLS (C-CELLS) - not easily seen on H&E sections.
Histology and cytology - primarily found among thyroid follicular epithelial cells (intrafollicular) but also between follicles (para or interfollicular). Distribution has been mapped in the human with immunoperoxidase method. They are found in the central part of the lateral lobes of the thyroid gland. C-cells normally have many secretion granules as well as RER and Golgi. They are depleted of granules by hypercalcemia. Secretion granules contain the peptide, calcitonin.
IV. Thyroid Stroma
Collagenic connective tissue forms a thin capsule that surrounds the gland and frequently encloses the superior parathyroid glands. Extensions of the capsule partially subdivide the gland into lobules and carry a rich network of fenestrated capillaries between the follicles.
A. Parathormone - functions
1. Stimulates osteoclastic activity and mobilization of calcium by osteocytes and osteoblasts.
2. Acts on kidneys to produce phosphaturia (loss of phosphate) also stimulates conversion of Vitamin D to its active form.
3. Active Vitamin D, increases absorption of calcium and phosphate from intestine.
B. Cells. Parathormone is probably produced by most of the cells in the parathyroid gland, but primarily by the chief cells.
1. Chief cells - small, slightly basophilic, with moderate development of ER, Golgi, and mitochondria. Membrane limited "secretion" granules are also evident but few in number. Thus there is not a large amount of hormone stored but is released as it is synthesized (constitutive secretion). Proteasomes have been implicated in regulating the amount of hormone produced by digesting unneeded precursors of parathyroid peptide.
2. Oxyphil cells - appear after 7 years of age; function unknown. ABUNDANT mitochondria.
C. Organization - mass of parenchymal cells permeated by numerous fenestrated capillaries subdividing parenchymal cells into irregular clumps or cords (occasionally small follicles). Capsule of the superior parathyroid is usually continuous with that of the thyroid gland. Partial C.T. septa increase with age, particularly fat cells.
SUPRARENAL HISTOLOGY
I. FOUR CLASSES OF HORMONE PRODUCED
A. From cortex
1. Mineralocorticoids (Aldosterone)
2. Glucocorticoids
3. Sex steroids
B. From medulla
1. Catecholamines (norepinephrine and epinephrine)
II. ORGANOGENESIS
A. Provisional or fetal cortex comes from mesothelium between dorsal mesentery and urogenital ridge. Begins at 5 weeks (8 mm). ACTH from fetus stimulates production of steroids, that are utilized by fetus and by the placenta for estrogen synthesis.
B. Definitive cortex differentiates from the blastema under the capsule when the fetal cortex involutes neonatally. It surrounds the medulla of the encapsulated glands that are embedded in the perirenal fat at the superior pole of each kidney. About 90% of the adrenal gland is cortex.
C. Medulla - neuroectoderm of sympathetic ganglion migrate in, beginning in 7th week to form chromaffin cells.
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1. Capsule (fibrous C.T.) 2. Zona glomerulosa 3. Zona fasciculata 4. Zona reticularis 5. Cortex (epithelial cells) 6. Medulla (epithelial cells) 7. Adrenal vein |
A. Zona glomerulosa - outer, relatively narrow zone (about 15% of cortex) of vacuolated (due to lipid droplets) cells arranged in arcades, clumps or knotty cords. Cells have abundant tubular smooth ER, well developed Golgi, and elongate mitochondria with shelf-like cristae. Produce mineralocorticoids, especially aldosterone, under control of renin-angiotensin system. ACTH has minimal effect.
B. Zona fasciculata - middle - most extensive zone (about 80% of cortex). Large fenestrated sinusoidal vessels surround parallel, branching and anastomosing cords of pale vacuolated cells. Oval mitochondria with tubular cristae and abundant SER characterize these cells. Cells typically contain many fat droplets, but ACTH stimulation of corticosterol secretion causes decrease of both lipid, including cholesterol, and of ascorbic acid. Hypertrophy and hyperplasia of fasciculata and reticularis but not glomerulosa also accompany ACTH treatment. Glucocorticoids (esp. Cortisol) and sex hormones are produced by both the fasciculata and reticularis.
C. Zona reticularis - narrow zone to medulla. Small cells, the darker ones have pyknotic nuclei and lipofuscin. They are irregularly arranged and tend to have elongate mitochondria. Otherwise these cells are similar in structure and function to those in the fasciculata.
IV. HISTOLOGY OF MEDULLA
A. Arrangement - chromaffin cells (pheochromocytes) of two varieties (epinephrine and norepinephrine secreting) are distributed along capillaries and venules among a network of veins forming the central or medullary vein.
B. Cytology - chromaffin cells are characterized by numerous membrane limited granules containing the catecholamines that are oxidized to a brown pigment when fixed in the presence of bichromate (chromaffin reaction). Run at acid pH, norepinephrine granules react preferentially demonstrating the two cell types, norepinephrine and epinephrine storing cells. Epinephrine is the major product of the medulla and epinephrine cells are the most numerous. Other substances found within the granules are chromogranins (amine carrier proteins), ATP and the enzyme that converts dopamine to norepinephrine.
C. Paracrine secretions: chromogranin a soluble protein is secreted with the catecholamines.
V. NERVE SUPPLY - mostly preganglionic sympathetics to the chromaffin cells. There are some postganglionic cells in the capsule and medulla. They may control vasculature.
VI. BLOOD SUPPLY
A. Sources - numerous small arteries from: 1) inferior phrenic; 2) celiac, and 3) renal arteries enter capsule and form subcapsular plexus.
B. Vessels arising from subcapsular plexus are: 1) capsular, 2) cortical sinusoids that drain into the medulla; and 3) medullary arterioles that go through the cortex to supply medulla. A single medullary vein drains the gland.
VII. CORTEX - MEDULLARY INFLUENCE: conversion of norepinephrine to epinephrine requires the enzyme phenyl-ethanolamine-N-methyl transferase. The activity of this enzyme is dependent upon high levels of corticoids. This is provided by venous blood coming from the cortex.
PINEAL HISTOLOGY
I. CELLS
A. Pinealocytes - lightly stained cytoplasm - many processes not demonstrated with H&E; nuclei relatively large with prominent nucleoli. Secretion granules contain melatonin.
B. Glial cells - less numerous than pinealocytes. They surround and mingle with the pinealocytes making up peculiar aggregates of cells separated from each other by extensions of pia mater. Aggregates have a variety of configurations--plates, cords, follicles.
II. INNERVATION - numerous postganglionic sympathetic nerves from the superior cervical ganglion.
III. FUNCTION - is not totally clear but produces melatonin.
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Last Revised: Tue, Nov 14, 2006