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THE ENDOCRINE SYSTEM Endocrine System Composed mainly of ductless glands Secretions pass directly into the blood

or lymph circulation Consists of widely separate seemingly unrelated glands, which differentiate from epithelial cells Have a rich supply of blood vessels Its secretions are delivered to nearly or distant sites of activity via the vascular system

The Three Forms of the Endocrine Components of the Body: a. Purely endocrine in function - Pituitary (Hypophysis) Gland, Thyroid Gland, Parathyroid Gland and Suprarenal Glands b. Scattered masses od endocrine tissue within exocrine glands or other organs - Islets of Langerhans, Interstitial Cells of Testis. Corpora Lutein of the Ovary and Juxtaglomerular cells of kidney Mixed Glands Liver exhibits endocrine and exocrine function c. Isolated endocrine cells

Lining epithelium of the Gastrointestinal and Respiratory Tracts terminal APUD (amine precursor, uptake decarboxylation) cells

Hormones may be secreted: 1. as rapidly as they are formed in some glands 2. when necessary in others or 3. stored until required These secretory patterns affect the microscopic and ultrastructure of the parenchymal cells. In some endocrine glands, the secretion accumulates within the cell of origin. In others, the secretory product is stored in a central vase surrounded by secretory cells. Thus, forming a follicle as in the thyroid gland. However, in the adrenal cortex, the secretion is released almost rapidly as it is formed. Embryological Derivation As a group, the Endocrine Glands are derived from all three germ layers in the embryo. a. The hypophysis, adrenal medulla and chromatin bodies are ectodermal origin. b. The adrenal cortex, testes and ovaries are derived from the mesoderm. c. Parenchymal cells of the thyroid, parathyroid and pancreatic islets of Langerhans arise from the endoderm. 3 Classes of Hormones based in their chemical composition: 1. Steroid Hormones Ex: Adrenocortical Hormones (Testosterone, Estrogen, Progesterone) - Secreted by Adrenal Cortex, Ovary and Testis 2. Protein Hormones Ex: Prolactin and Insulin - Secreted by Hypophysis, Pancreas, Thyroid and Parathyroid 3. Amino acid analogues and derivatives Ex: Thyroxine and Norepinephrine - Secreted by the Thyroid and Adrenal Medulla Hormones - Discharged from cells of endocrine glands into the blood or lymph circulation - Has an effect upon a particular tissue or organ or upon the body as whole - Some affect certain tissue or organs specifically: the organs affected are termed target organs or receptors. - Some do not enter target cells but instead bind to receptors on the cell membrane activating an enzyme, adenlylcyclase. Adenlylcyclase membrane enzyme increases intracellular concentrations of cyclic adenosine monophosphate (CAMP) which acts as a second messenger; to initiate the physiological response for which the particular cell is programmed. Neuro-endocrine system Many hormones produce an effect upon the nervous system: some endocrine cells are regulated by neural mechanisms. This overlapping regulatory control that includes endocrine and nervous components is regarded by many as a single system.


The hypothalamus is located near the center of the brain, above the brainstem and below the cerebrum. Its primary function is to maintain homeostasis, acting as the bodys thermostat. The nervous system and endocrine system are truly integrated structurally and functionally in the hypothalamus. The hypothalamus receives chemical and nervous input about sight, sound, taste, smell, temperature, blood glucose concentrations, and salt/water balance. It also helps control hunger and thirst as well as mating and sexual behavior. The hypothalamus also has nervous input to functions such as the regulation of heart rate, blood pressure, and contractions of the urinary bladder. The hypothalamus controls the pituitary gland, which is attached to the underside of the brain by a slender stalk. The pituitary gland, also called the hypophysis (hi-POF-ih-sis; Greek for to grow under), sits in a pocket of bone called the sella turcica (Turks saddle), which is located directly above the palate of the mouth and behind the bridge of the nose. In the past, the pituitary has been called the master gland because it controls many other endocrine glands, but this term is no longer widely used. The word pituitary is derived from the Latin pituita, or phlegm, because early anatomists believed this gland produced saliva. The pituitary regulates the thyroid gland, adrenal glands, and the reproductive organs. It also produces hormones that control growth and kidney function, are involved in milk production, and are related to childbirth. The pituitary gland has two parts: the anterior (adenohypophysis) and the posterior pituitary (neurohypophysis). During embryonic development, a fold of tissue moves up from the roof of the mouth and forms the anterior pituitary. A piece of the hypothalamus bulges downward to form the posterior portion. The two pieces of tissue join to create the pituitary gland. The anterior portion is physically separate from the brain, but is connected to it by a special type of blood circulation, called the hypophyseal portalor shunt. Capillaries in the hypothalamus join to form a vein that enters the pituitary gland and then separates to form capillaries. This system of circulation allows blood to pick up chemicals called controlling factors that are released in the hypothalamus and carry them directly to the pituitary gland, where they control the release of hormones. Every pituitary gland hormone has at least one releasing factor or hormone and some have both inhibiting and releasing factors. The following hormones are released by the anterior pituitary: Growth Hormone Stimulates bone and muscle cells to grow. Prolactin causes the mammary glands to produce milk. Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH), known collectively as gonadotropins, stimulate hormone and gamete production by the gonads (testes and ovaries). Thyroid Stimulating Hormone (TSH) causes thyroid to produce thyroid hormone.

Adrenocorticotropic Hormone (ACTH) stimulates the adrenal cortex to produce corticosteroids, especially during periods of stress. Melanocyte Stimulating Hormone (MSH) may have a role in fat metabolism. Endorphins, which are also produced by the brain, reduce the perception of pain.

The posterior pituitary is an extension of the brain. It releases two hormonesoxytocin and antidiuretic hormone (ADH)that are made in specialized cells in the hypothalamus. The hormones are transported down nerve cells into the pituitary, where they are stored. The hypothalamus signals for their release by direct nerve signals to allow for quicker secretion. Oxytocin stimulates the uterus to contract during labor and stimulates the breast to start releasing milk when a baby nurses. Antidiuretic hormone reduces urine output by acting on the collecting ducts of the kidney. ADRENAL GLANDS

The adrenal glands sit above the kidneys (ad means near and renal means kidney). They are slightly triangular in shape and weigh about 4 g (0.14 ounces; about the same as a persons thumb). There are two distinct regions: the cortex, or outer layer, and the medulla, or inner region. During embryonic development, two separate cell populations migrate to the region near the kidneys and form the adrenal glands. One population is from nervous tissue and forms the adrenal medulla, or middle. The outer layer of cells forms the adrenal cortex, which is controlled chemically by the anterior pituitary gland. `The gland is enclosed in a connective tissue capsule that gives a numerous delicate radial trabeculae, consisting principally of reticular fibers into the cortex. Capillaries penetrate into the gland along the delicate trabeculae that divide the parenchymal cells of the organ into varying characteristic cell group. The adrenal medulla secretes epinephrine (adrenaline) and norepinephrine (noradrenaline). These hormones are released during periods of stress, causing the response known as fight-or-flight. The adrenal gland secretes four groups of steroids, known ascorticosteroids: estrogens (female sex hormones), androgens (male sex hormones),glucocorticoids, andmineralocorticoids. Released during times of stress, glucocorticoids raise blood glucose levels, decrease inflammation, and delay healing. Mineralocorticoids work on the kidneys to increase sodium and water reabsorption. `Adrenal Cortex is classically 3 zones: The Zona Glomerulosa is the thin outer zone just beneath the capsule consisting of closely packed clusters and arcades of columnar cells arranged in spheroidal group which normally show no central lumen or in hooked horse shoe shaped form or slightly coiled columns. These are continuous with the cell of the zona fasciculata.

The Zona Fasciculata is the thick middle layer of the adrenal cortex. It is the broadest zone composed of cell cords coursing parallel to one another in a radial direction toward the medulla. The Zona Reticularis is the thinnest and least distinct of the three zones of the cortex. The cell chords form anastomosing network. Like the cells of the zona fasciculate, the cells in this zone possess an abundance of the agranular variety of endoplasmic reticulum. Adrenal Medulla The boundary between the zona reticularis of the cortex and the medulla is usually irregular in man with some columns of cortical cells projecting into the medulla. Cells of the medulla are large epitheloid, ovoid or polyhedral arranged in rounded groups or short anastomosing cords surrounded by venules and capillaries. Hormones and Function Zona Glomerulosa secretes hormones called: Mineralocorticoids, which are concerned with fluid and electrolyte balance. Cells of Zona Fasciculata and reticularis secrete Glucocorticoids, which are concerned with the metabolism of carbohydrates, proteins and fat, and Steroid hormones. Adrenal Medulla hormones are catecholamines which are: epinephrine, which is a vasoconstrictor, has relatively very little effect upon metabolism but causes a marked increase of the blood pressure with very little effect cardiac output, and norepinephrine. Regeneration Cells of the adrenal cortex show a considerable capacity for regeneration in comparison to those of the medulla. In the regenerating gland, cells functionally similar to those of the normal zona fasciculate and reticularis differentiate from cells of the zona glomerulosa.

PINEAL GLAND - Slightly flattened, cone-shaped appendage of the brain - 8 to 12 mm in length, 5 to 8 mm in width - Base is constricted to form a hollow peduncle by which is attached to the roof of the 3rd ventricle with the pineal recess extending up to it - Covered by the pia mater except at its attachment, forming a thin capsule from which connective tissue trabeculae invaginate the parenchyma of the organ dividing into poorly defined lobules - Its capsule and trabeculae carry numerous blood vessels and nerves

Functions: - An inhibitory action on the development and maturation of the gonads (anti-gonadotropic function) - A modulating influence on reproduction tending to suppress gonadal development - Part of a neuro-endocrine mechanism regulating the gonads and other organs, in response to light - Possible relations to the Pituitary, Adrenal Cortex and Thyroid functions 2 Types of Cells in the Parenchyma: 1. Pinealocytes or Chief Cells or Epitheloid Cells - Cords of pale staining epitheltoid cells with large nuclei and prominent nucleoli - Constitute the bulf of the organ - Cytoplasm usually stains in H&E preparations - Irregular shape which can be demonstrated after the del Rio-Hortega silver method - Have long tortuous cytoplasmic processes radiating from the cords toward the connective tissue septa with club-shaped terminations or bulbous swellings on or near blood vessels In Electron micrographs, - Numerous free ribosomes in the cytoplasm - Abundant tubular and vesicular elements of atypical agranular endoplasmic reticulum - Moderately abundant fairly large mitochondria - grumose bodies dense-cored, membrane bounded granules, reminiscent of primary lysosomes Distinctive Features in the cytoplasm - Abundant microtubules - Lipid droplets - Lipochrome pigments - Lysosomes 2. Interstitial cells or Neuroglia cells or Supportive Cells (epiphyseal gliocytes) - 5% of the cells in the pineal body - Found in the perivascular area, between the clusters of pinealocytes - Nuclei are elongated and stain more deeply than parenchymal cells - Cytoplasm is more basophilic - Cytoplasm is drawn out into long processes or extensions surrounding pineal cells as well as, sympathetic nerves and nerve endings - Abundance of filaments in their cytoplasm In Electron micrographs, - Numerous free ribosomes - Granular E/M - Occasional deposits of glycogen - Rare microtubules - Mitochondria are small - Endoplasmic Reticulum is rough surfaced Corpora Arenacea (Brain sand, Psammona bodies, Acervulus Cerebri, Sand Granules)

The pineal body often contains mulberry-shaped concretions which are extracellular, lamellated bodies composed of concentric layer of a mineralized organic matrix. The concretions are composed mainly of calcium phosphates and carbonates. They increase gradually in size and number, being quite numerous in old age. Nerves Some of the nerve processes present in the pineal body are mylinated., but most are non-myelinated. The myelinated fibers are derived from the trabecular and posterior commissures, whereas the non-myelinated nerve processes come from sympathetic fibers originating in the posterior cervical ganglia. The beaded non-myelinated nerves and their endings have accumulations of vesicles that contain norepinephrine and serotonin. PANCREAS (Endocrine portion) Throughout the endocrine portion of the pancreas are scattered richly vascularized small masses of endocrine cells known as the pancreatic islets of Langerhans. Their secretion, insulin is poured directly into the blood stream, having no functional communication with the duct system of the gland. In ordinary H&E preparations, the islets appear as more or less spheroidal masses of pale staining cells, arranged in the form of irregular anastomosing cords. Closely applied to the epithelial cells between the cords are numerous blood capillaries. The islet cells are paler staining than the surrounding acinar cells. The islets are more or less completely demarcated from the surrounding acinar tissue by a thin reticulum containing abundant blood capillaries. The number of islets varies in different portions of the glands as well as in different individuals. They are more abundant in the tail of the pancreas than in the head.

3 types of Granular cells distinguished through special stains such as Mallory-azan: a. Alpha cells (A cell) - Contain granules that are insoluble in alcohol - Granules are relatively large and colored brilliant red - Less numerous - Situated around the periphery of the islet - Most striking due to the abundant dense spherical granules - Has few cisternal profiles of granule endoplasmic reticulum, juxta nuclear Golgi complex and some mitochondria

Elaborate glucagon which elvate the blood sugar level

b. Beta Cells (B cell) - Contain fine granules that are soluble in alcohol but not in water - Located in the interior of the islets but may also occur outside the islets - Smaller and stain brownish orange, with Mallory-azan staining method - 60-90% of all islet cells - Has a very distinct appearance - Contain one or small dense crystals which are rectangular or polygonal with a periodic internal structure and surrounded by a matrix - Mitochondria are larger, Golgi complex are more prominent and Endoplasmic Reticulum is less extensive - It is where Insulin is synthesized Insulin plays an important role on carbohydrate metabolism. It promotes glycogenesis and utilization of glucose. c. Delta Cells - Contains small blue-staining granules by Mallory-azan methods - Granules are slightly larger and less dense than the alpha granules

Gland Hypophysis Pars Distalis

ENDOCRINE SECRETIONS Hormone Source Functions STH (Somatotropin) Somatotrope (acidophil) Promotes body growth, particularly growth of long bones LTH (Prolactin) Mammotrope Promotes mammary (acidophil) gland development and lactation TSH (Thyrotropin) Thyrotrope (basophil) Stimulates production of thyroid hormones FSH Gonadotrope (basophil) Stimulates growth of ovarian follicles in female and promotes spermatogenesis in male LH (ICSH) Gonadotrope (basophil) In female: stimulates ovulation and formation of corpus luteum. In male: promotes androgen secretion ACTH Cornicotrope (basophil) Stimulates secretion of glucocorticoids by suprarenal cortex LPH Cornicotrope (basophil) Unknown in humans



Neurons in paraventricular and supraoptic nuclei

ADH (vasopressin)

Neurons in paraventricular and supraoptic nuclei


Thyroid hormones (T3 and T4)

Principal Cell


Parafollicular cell



Principal cell (plus oxyphil)

Suprarenal Cortex

Mineralcorticoids (principally aldosterone) Glucocorticoids (principally cortisol)

Zona glomerulosa cells

Zona fasciculate and zona reticularis cells

Gonadocorticoids (sex steroids) Suprarenal medulla Epinephrine

Zona reticularis cells

Chromaffin cell

Norepinephrine Paraganglia Pineal Norepinephrine Melatonin

Chromaffin cell Chief cell Pinealocyte

Induces contraction of smooth muscle in uterus and of myoepithelial cells in the mammary glands Promotes water resorption and conservation, and causes contraction of vascular smooth muscle Regulates basal metabolic rate and influences body growth and development Lowers blood calcium levels by inhibiting bone resorption Raises blood calcium levels by promoting bone resorption and increasing calcium resorption in the kidneys Increase reabsorption of sodium by kidney tubules Promote carbohydrate metabolism and suppress inflammatory and Immune responses (Amount too small to produce significant effects) Increases oxygen consumption and mobilizes glucose Increases heart rate, blood pressure Function unclear but may influence gonadal dvelopment Plays an important role in carbohydrate metabolism Causes elevation of blood sugar level

Islets of Langerhans


Beta cells (B)


A cells (alpha)


Androgens (Testosterone)

Interstitial cells of Leydig

Ovaries Follicle cells


Theca interna

Corpus Luteum


Lutein cells (large)

Kidney (juxta glomerular apparatus)


Juxta glomerular cells

Essential for development of secondary sexual characteristics Induces growth cell development of mammary gland and female reproductive tract Causes uterine tract to secrete Renders mucosa receptive to nidating ovum Influences blood pressure