ENDOCRINE SYSTEM

 Endocrine System and Nervous System are the two major integration and control systems of the

body.

Endocrine System and Nervous System works in parallel with, but independently from each other.

 Endocrine System responds slowly to stimuli.

 Some parts of the nervous system such as hypothalamus are also endocrine organs.

 Endocrine system is composed of ALL the endocrine cells in the body or those cells that produce

substances called HORMONES

 Hormones are secreted into capillaries and carried by blood to target organ/s or tissue/s that

contain/s the cells (target cells) that possess appropriate receptors for them
Endocrine System

 The endocrine cells in the body occur:

1) Embedded singly or in clusters in the various organs such as the juxtaglomerular cells in the kidney,

enteroendocrine cells in the GIT, and interstitial cells of Leydig in the testes

2) As distinct organs called endocrine glands, e.g., pituitary, thyroid, parathyroid, adrenal, and pineal;

and;

3) As component structures of certain organs, e.g., the endocrine areas of the hypothalamus and islets

of Langerhans of the pancreas.

HYPOTHALAMUS

 The hypothalamus is part of the brain.

 It is a component of the diencephalon, which together with the telencephalon comprises the

forebrain prosencephalon.

 The hypothalamus is located at the base of the brain, behind the optic chiasm, and it forms the

floor and part of the wall of the third ventricle.

 It consists of 11 major nuclei, nuclear areas and tracts.

 The hypothalamus controls numerous bodily functions including many vegetative ones such as

thirst, hunger and satiety, temperature, sexual behavior, and circadian rhythms.

 In addition, it produces two groups of hormones: posterior pituitary and hypophysiotropic.

HYPOTHALAMUS: Posterior Pituitary Hormones

 The posterior pituitary hormones are oxytocin and antidiuretic hormone (ADH; vasopressin).

They are synthesized by neurons (magnocellular secretory neurons) that are in the supraoptic and

paraventricular nuclei of the hypothalamus, but stored in the posterior lobe of the pituitary gland,

thus, their collective name.

 The supraoptic nucleus is located above and lateral to the optic chiasm while the paraventricular

nucleus is in the lateral wall of the third ventricle.

 Oxytocin is produced by one cell type while ADH is produced by another cell type. But both cell

types are present in the supraoptic and paraventricular nuclei.

 The main target organs of oxytocin in women are the uterus and breasts (mammary glands).

 In the uterus, it stimulates contraction of the smooth muscles in the myometrium, and thus, aids

in parturition (i.e., delivery of the fetus).

 In the mammary glands, it promotes ejection of milk during lactation by stimulating contraction

of the myoepithelial cells that surround the alveoli.

 Oxytocin's function in non-pregnant women is not fully understood yet, but it may play a role in

various social behaviors and even wound healing. In males, current evidence suggests that

oxytocin facilitates sperm transport within the male reproductive system and stimulates

production of testosterone by the testes.

  The target organs of ADH, on the other hand, are the kidneys. It is secreted in response to

increased blood tonicity, sensed by osmoreceptor cells in the hypothalamus. It increases

permeability of the distal and collecting tubules of the kidneys, leading to the formation of more

concentrated urine.

HYPOTHALAMUS: Hypophysiotropic Hormones

The hypophysiotropic hormones whose names describe their main functions include:

1) corticotrophin-releasing hormone (CRH),

2) Thyrotropin-releasing hormone (TRH),

3) growth hormone-releasing hormone (GRH),

4) Gonadotropin-releasing hormone (GnRH; luteinizing hormone-releasing hormone; LHRH),

5) growth hormone-inhibiting hormone (GHIH; somatostatin; SS), and

6) prolactin-inhibiting hormone (PIH).

 The hypophysiotropic hormones are synthesized by secretory neurons (parvocellular secretory

neurons) that are smaller than the neurons that produce the posterior pituitary hormones. The

parvocellular secretory neurons are widely distributed within the hypothalamus but they are

mostly in the arcuate, paraventricular & periventricular nuclei.

  The function of the hypophysiotropic hormones is to regulate the activity of the secretory cells of

the pituitary gland.

PITUITARY GLAND

 The pituitary gland is a small but very important endocrine gland. It is an ovoid body that weighs

merely 500 mg and is only about 12 mm in transverse and 8 mm in AP diameters. It is attached to

the inferior surface of the hypothalamus and is lodged in a concavity (hypophyseal fossa) in the

sella turcica of the sphenoid bone.

 The pituitary gland consists of two distinct parts, neurohypophysis and adenohypophysis which

differs developmentally, structurally and functionally.

DEVELOPMENT OF PITUITARY GLAND:

The neurohypophysis arises from neural ectoderm. It develops as a downgrowth of the diencephalon. The

adenohypophysis arises from oral ectoderm; it is derived from Rathke's pouch, an upgrowth of the oral

mucosa. During embryonic development, the two ectodermal outgrowths meet and fuse to form the

pituitary gland. The connection of Rathke's pouch to the oral cavity is subsequently severed, but the

connection of the neurohypophysis to the base of the brain, specifically to the hypothalamus, persists.

PITUITARY GLAND: Neurohypophysis

 The neurohypophysis has three regions:

1) Median eminence;

2) Pituitary stalk (infundibulum; infundibular stem; infundibular stalk; hypophyseal stalk); and

3) Posterior lobe (pars nervosa, infundibular process)

 The median eminence is the proximal portion of the neurohypophysis that is attached to the

hypothalamus. The slender downward continuation of the median eminence is the pituitary stalk,

while the expanded inferior continuation of the pituitary stalk is the posterior lobe. Incidentally,

some authors consider the median eminence as the most inferior part of the hypothalamus,

instead of being the proximal portion of the neurohypophysis.

 The easiest way to understand the histology of the neurohypophysis is to consider it as simply the

downward extension of the hypothalamus.

 The cell bodies of the secretory neurons in the hypothalamus (e.g., parvocellular secretory

neurons and magnocellular secretory neurons) are located in the nuclei and nuclear areas, but

their unmyelinated axons travel downwards, leave the hypothalamus and terminate in the

neurohypophysis.

 The unmyelinated axons of the parvocellular secretory neurons are relatively short.

 They terminate in the median eminence. The axonal terminations are where the hypophysiotropic

hormones that are synthesized by the cells are stored.

 The axons, together with the numerous capillaries and supporting cells that are associated with

them, comprise the median eminence.

 The unmyelinated axons of the magnocellular secretory neurons, on the other hand, are much

longer than those of the parvocellular secretory neurons. They originate from the nuclei (i.e.,

supraoptic and paraventricular) where the cell bodies are located, pass through the pituitary stalk,

and end in the posterior lobe of the pituitary gland.

 In the pituitary stalk, the proximal segments of the axons comprise the hypothalamo-hypophyseal

tract, the main component of the pituitary stalk.

 In the posterior lobe, the distal segments of the axons comprise the bulk of the lobe.
 The axons of the magnocellular secretory neurons have dilatations, not just at their ends but along

their entire length. The dilatations are the storage sites for the secretory granules.

 They are associated with capillaries into which their secretions are released, as needed. The

posterior lobe is much bigger than the pituitary stalk simply because most of the axonal dilatations

are in the former.

 Aggregations of secretory granules in the axonal dilatations are often seen in routine LM

preparations of the posterior lobe and pituitary stalk as deeply-staining, basophilic structures

called Herring bodies.

 In the neurohypophysis, the supporting cells are called pituicytes. They surround the axons of the

secretory neurons. Pituicytes are non-secretory cells that are morphologically similar to

astrocytes. They are stellate and their slender cytoplasmic processes are interconnected with

those of other pituicytes by gap junctions. Aside from pituicytes, the only other cellular elements

in the neurohypophysis are the endothelial cells of, and the blood cells in, the sinusoids.

 In brief, the neurohypophysis is simply the downward continuation of the hypothalamus. It

consists of: a) axons of the secretory neurons whose cell bodies are in the hypothalamus,

b) pituicytes, and c) sinusoids.

  The neurohypophysis is not a gland. It does not produce but only stores and releases (secretes)

hormones.

PITUITARY GLAND: Adenohypophysis

 The adenohypophysis is the part of the pituitary gland that produces hormones.

 Whereas the neurohypophysis is more fibrous than cellular, the adenohypophysis is more cellular

than fibrous.

 The adenohypophysis has three regions: a) anterior lobe (pars distalis); b) pars tuberalis (pars

infundibularis); and c) intermediate lobe (pars intermedia).

 The pars tuberalis forms a thin and incomplete sleeve around the pituitary stalk of the

neurohypophysis. It is inferiorly continuous with the anterior and intermediate lobes.

PITUITARY GLAND: Anterior Lobe

 The anterior lobe comprises about 70% of the pituitary gland. Nearly all the hormones produced

by the pituitary gland come from this lobe. The hormones produced by the anterior lobe (anterior

pituitary hormones) have wide-ranging effects. They regulate almost all other endocrine glands,

and the ovaries, testes and mammary glands. They are also involved in the metabolism of muscle,

bone, and adipose tissue.

 Histologically, the parenchyma of the anterior lobe consists of epithelial cells, most of which are

secretory in nature. The parenchymal cells form irregularly-arranged anastomosing cords and

clusters that are surrounded by fenestrated sinusoids. A minimal amount of reticular tissue exists
 between the epithelial cells and the sinusoids. It serves as the supporting structure (stroma) for

the cell cords and the sinusoids.

PITUITARY GLAND: Anterior Lobe’s Parenchymal Cells

 In LM sections prepared with the use of acid dyes, the parenchymal cells in the anterior lobe of

the pituitary gland can be classified into two general types-chromophils, whose cytoplasm is

intensely colored and chromophobes, whose cytoplasm is pale staining. The chromophils

comprise about 35% while the chromophobes comprise about 65% of the parenchymal cells.

 The chromophils are further classified into 1) acidophils (alpha cells) and 2) basophils (beta cells).

The cytoplasm of acidophils stains red with acid dyes while that of basophils stains blue or purple.

In addition, the nucleus of the basophils is less dense, and is thus, lighter-staining than that of the

acidophils.

 The staining characteristics of the chromophobes and chromophils in LM preparations have

nothing to do with true acidophilia or basophilia because all the dyes used are acid dyes.

Furthermore, the dyes are taken up mostly by the secretory granules of the cells and not by the

organelles.
PITUITARY GLAND: Chromophils

 Electron microscopy and histologic studies utilizing special techniques have shown that there are

actually five-not just two-types of chromophils.

 The classification of the chromophils into five types is based on the hormone that the cells secrete

and their appearance in electron micrographs. The cell types, which have been named after the

hormones they produce, are the:

1) Somatotrophs (STH cells),

2) Mammotrophs (lactotrophs),

3) Thyrotrophs,

4) Corticotrophs, and

5) Gonadotrophs.

The somatotrophs and the mammotrophs are the acidophils while the thyrotrophs, corticotrophs, and

gonadotrophs are the basophils of traditional light microscopy.

PITUITARY GLAND: Chromophobes

 Electron microscopy and histologic studies utilizing special techniques have shown that most

chromophobes are actually chromophils (mostly corticotrophs), but they have pale cytoplasm in

routine LM preparations because they are resting, or have just recently released most of their

secretory granules, or are still in the process of producing new ones. In other words, the few

secretory granules they possess are inadequate to impart enough cytoplasmic coloration to

distinguish them as chromophils under the LM with the use of traditional acid dyes.

 There are, however, two kinds of chromophobes that are not chromophils. One type, the

folliculostellate cell (FS cell), has long, branching processes. It is non-secretory and performs

some supportive role for the other cells. The second type is an undifferentiated stem cell.

PITUITARY GLAND: Hypothalamic Control over the Anterior Lobe of the Pituitary Gland

 The Anterior Lobe of the Pituitary Gland secretes SIX important hormones, namely:

1) Somatotropin, 2) prolactin, 3) thyrotropin, 4) corticotrophin, 5) FSH, and 6) LH

* The secretion of these hormones is mainly regulated by the hypothalamus through the hypophysiotropic

hormones.
PITUITARY GLAND: Pars Tuberalis

 The pars tuberalis is separated from the pituitary stalk by connective tissue that is continuous

with the pia-arachnoid membrane of the brain.

 The pars tuberalis is more vascular than the anterior lobe. This is because the blood vessels that

comprise the hypophyseoportal system traverse it.

 Its parenchymal cells are mostly gonadotrophs and thyrotrophs that are arranged parallel to the

blood vessels in cords, clusters, and as lining cells of colloid-containing follicles, which are often

present in the region.

PITUITARY GLAND: Intermediate Lobe

 The intermediate lobe of the pituitary gland is the thin and poorly developed region of the gland

that is in between the posterior lobe and the anterior lobe.

 Its boundary with the anterior lobe is demarcated by a groove to the original lumen of Rathke's

pouch.

 The intermediate lobe is better developed in the fetus than in adults, where it is rudimentary. In

routine histologic sections, it is easy to recognize because of the presence of follicles (Rathke's

cysts) that contain eosinophilic colloidal material.

 The parenchymal cells of the intermediate lobe form irregular clusters. They contain some fine

secretory granules. They synthesize melanocyte- stimulating hormone (MSH), whose production

in adults is minimal to nil. MSH probably plays a role in melanin production by melanocytes. An

increase in MSH results in darker skin. MSH increases in humans during pregnancy. This, along

with increased estrogens, causes increased pigmentation in pregnant women.

PINEAL GLAND

 The pineal gland is a small (8 mm long; about 120 mg in weight) conical structure whose base is

attached to the posterior portion of the roof of the third ventricle of the brain by two short stalks.

DEVELOPMENT OF THE PINEAL GLAND

 The pineal gland arises in the embryo as a hollow evagination of the roof of the diencephalon. As

it develops, its cavity gets filled with cells and eventually the gland transforms into a solid organ.

The pineal gland is well-developed in children. At puberty, it starts to involute.

PINEAL GLAND

 The pineal gland is enveloped by a thin connective tissue capsule that is derived from pia mater.

 Connective tissue septa arise from this capsule and incompletely divide the gland into irregular

lobules. The tissue septa also serve as passageways for blood vessels and unmyelinated nerve

fibers.

 The parenchymal cells that fill the lobules of the pineal gland are mostly pinealocytes, which are

actually modified neurons. They comprise 95% of the cell population of the gland. In the lobules,

they are arranged in short cords or in clusters that are surrounded by fenestrated capillaries.

 In routine histologic preparations, pinealocytes have poorly defined borders and basophilic

cytoplasm.

 Dispersed among the pinealocytes are supporting cells called interstitial cells. These cells are

smaller than pinealocytes. They are morphologically similar to astrocytes.

 Aside from pinealocytes and interstitial cells, mast cells are also often seen in the pineal gland, a

fact that may explain the organ's high histamine content.

 One striking histologic feature of the pineal gland is the presence of extracellular bodies, called

brain sands (acervuli, psammoma bodies, or corpora arenacea), within the lobules. These are

calcified bodies that have a concentric lamellar structure. This is why the pineal gland is visible

and is sometimes used as a landmark in X-ray studies of the brain. With age, the interstitial cells

increase in number and hyalinization of parts of the pineal gland occurs.

HORMONE PRODUCED BY THE PINEAL GLAND

 The pineal gland produces the hormone melatonin whose secretion is stimulated by darkness and

inhibited by light.

 Melatonin is synthesized by the pinealocytes. It is a very important hormone in animals that breed

seasonally because it regulates the animals' sexual development, reproductive cycle (seasonal

breeding), hibernation, and other metabolic processes.

 In humans, melatonin blood level has a diurnal pattern (i.e., it is higher at night than during the

day); and is much higher in children than in adults. The diurnal fluctuation in blood melatonin

levels probably affects sleep patterns and rhythmic changes in the activity of the hypothalamus,

pituitary gland, and other endocrine tissues.

 Melatonin is also associated in the development of seasonal affective disorder, a condition that is

characterized by depression during winter, in countries where there is one.

THYROID GLAND

 The thyroid gland is the largest of the endocrine glands. It is 25 to 40 g in weight and is slightly

bigger in women than in men. It is an unpaired gland that lies on the anterior aspect of the neck.

 Grossly, it consists of two lateral lobes (right and left) and an isthmus.

 The lateral lobes are broad, inferiorly, but tapered, superiorly. They adhere to the lateral (one on

each side) aspects of the pharynx, larynx, esophagus, and trachea. Their inferior borders are at

the level of the sixth tracheal cartilage. The lateral lobes are connected to each other by a narrow

horizontal bridge of glandular tissue, the isthmus, which extends across the trachea usually in

front of the second and third tracheal cartilages. In some individuals, the thyroid gland also has a

small pyramidal lobe, which consists of glandular tissue that projects upward from the isthmus.
DEVELOPMENT OF THE THYROID GLAND

 The thyroid gland arises during early embryonic life as an epithelial invagination at the base of the

tongue. It migrates downwards and reaches its final position in the lower part of the neck in the

7th week of intrauterine life. It remains connected for a time to the base of the tongue by the

thyroglossal duct, which later disappears. The point of origin of the thyroid gland is indicated by

the foramen cecum, the apex of the sulcus terminalis, the V-shaped furrow that separates the

anterior from the posterior tongue.

THYROID GLAND

 The thyroid gland is enclosed by two capsules, an outer capsule that is derived from the

pretracheal layer of the deep cervical fascia and a true capsule that closely invests the gland and

sends connective tissue septa into the organ to form poorly-defined lobules.

 The connective tissue septa also serve as pathways for blood and lymph vessels and nerves.

 The connective tissue within the thyroid gland is infiltrated by lymphocytes and small lymphoid

nodules are occasionally seen.

 Each thyroid lobule is filled with irregular spherical, cystic structures, called follicles (thyroid

follicles), that are surrounded by fenestrated capillaries and supported by a thin connective tissue

stroma-consisting primarily of reticular fibers and cells-that is continuous with the septa.

 The follicles are 0.02 to 0.9 mm in diameter. Their cavity is occupied by a homogenous, gel-like

material known as colloid (thyroid colloid), while their wall is formed by a simple epithelium.

 Two types of cells comprise the simple epithelium that forms the wall of thyroid follicles: follicular

cells (principal cells) and parafollicular cells (mitochondria rich cells; C cells; clear cells).
 Follicular cells make up the overwhelming majority of the epithelial cells in the thyroid follicle. In

routine histologic preparations, they are seen as having a round nucleus that contains fine

chromatin material and one or two nucleoli, and a slightly basophilic cytoplasm.

 The luminal surface of follicular cells is provided with numerous microvilli, but these are not

discernible under the LM. The shape of the follicular cells and the staining property of the colloid

depend on the functional state of the follicle.

 In inactive follicles, the epithelial cells are squamous or cuboidal and the colloid is acidophilic. In

active follicles, the epithelial cells are tall cuboidal or columnar, and the colloid is basophilic.

 Parafollicular cells comprise only 0.1% of the epithelial cell population of the thyroid follicle. They

are scattered singly or in small groups in the epithelium.

 The parafollicular cells rest on the basal lamina of the epithelium but unlike follicular cells, their

apices do not touch the colloid. In routine histologic preparations, they are easy to identify

because they are much bigger and lighter-staining than follicular cells. Their cytoplasm contains

numerous small secretory granules.

HORMONES PRODUCED BY THYROID GLAND:

 The hormones produced by the thyroid gland are thyroxine (T4) and triiodothyronine (T3), which

are collectively referred to as thyroid hormones, and calcitonin.

 The production and secretion of the thyroid hormones (T3 and T4) are functions of the follicular

cells but the follicular cells do not directly synthesize the hormones. What they synthesize is

thyroglobulin, a large glycoprotein, which they discharge by exocytosis into the colloid. They

likewise collect iodine from the blood in the capillaries that surround the follicles and transport it

to the lumen of the follicle.

 In the colloid, some of the tyrosine residues present in the thyroglobulin get iodinated and

condensed to form the two principal thyroid hormones, thyroxine (T4) and triiodothyronine (T3),

with the aid of the enzyme thyroid peroxidase.

 T3 and T4 remain bound to thyroglobulin until they are to be secreted. During which, the follicular

cells ingest colloid by endocytosis, hydrolyze the peptide bonds that bind the thyroid hormones

to the thyroglobulin, and release the thyroid hormones into the capillaries.

 The thyroid hormones regulate the metabolism of proteins, carbohydrates, fats, and some

vitamins.

 Control of T3 and T4 secretion is the function of thyrotropin (TSH) that comes from the pituitary

gland.
 Calcitonin (thyrocalcitonin), on the other hand, is synthesized and secreted by the parafollicular

cells. It lowers blood calcium level by suppressing the bone resorption activity of the osteoclasts.

Incidentally, calcitonin is probably also secreted by other still unidentified cells of the body

because it is present in the blood of people who have had their thyroid gland surgically removed.

 The secretory activity of the parafollicular cells is regulated directly by blood calcium level. A high

blood calcium level stimulates while a low blood calcium level suppresses secretion of calcitonin

by the parafollicular cells.

PARATHYROID GLAND

 The parathyroid glands, usually two pairs (superior and inferior), are yellowish-brown, tiny, ovoid

bodies that are attached to the posterior surface of the lateral lobes of the thyroid gland.

 Each parathyroid gland is about mm long, 3-4 mm wide & 1-2 mm thick, & about 50 mg in weight.

DEVELOPMENT OF THE PARATHYROID GLAND

 The inferior parathyroid glands arise in the embryo from the third pharyngeal pouch together

with the thymus. When the thymus descends into the thoracic cavity, it pulls the inferior

parathyroid glands with it, but the latter do not descend all the way to the thorax. They come to

rest on the posterior surface of the thyroid gland. Occasionally though, parathyroid glands are

found in the company of the thymus in the thoracic cavity.

 The superior parathyroid glands, on the other hand, arise from the fourth pharyngeal pouch and

attach themselves to the thyroid glands as the latter migrates downward to the inferior portion

of the neck.
PARATHYROID GLAND

 The parathyroid glands lie within the capsule of the thyroid gland, but deep to the thyroid capsule,

each parathyroid gland is enveloped by its own thin connective tissue capsule. From this latter

capsule, connective tissue septa arise and divide the gland into poorly-defined lobules.

 In the lobules, the stroma is formed by delicate reticular tissue.

 The parenchyma of the parathyroid gland consists of epithelial cells that are arranged in cords

and clusters that are surrounded by fenestrated capillaries.

 Adipose cells are also relatively abundant within the lobules of the parathyroid gland where they

intermix with the parenchymal cells. Adipose cells are hardly present in the parathyroid glands of

newborns. They start to appear during childhood and by the age of 25 years they comprise about

30% of the volume of the gland. The adipose cells further increase in number with age.

 Follicles are occasionally present in the parathyroid glands, especially in older individuals. These

follicles resemble those found in the thyroid gland.

PARATHYROID GLAND’s

Parenchymal cells

 Two main types of parenchymal cells exist in the parathyroid gland: chief cells (principal cells) and

oxyphil cells (acidophil cells).

 Chief cells comprise majority of the parenchymal cells. A chief cell is a relatively small (8 to 10

mm, in diameter) polyhedral cell. In routine histologic preparations, its nucleus is prominent,

rather large, and vesicular.

 Its homogenous cytoplasm is faintly eosinophilic and it contains small, secretory granules that in

electron micrographs, are seen to be membrane- bound.

 Oxyphil cells are absent in children. They appear shortly before puberty and increase in number

with age. They occur singly or in clusters in the lobules. An oxyphil cell is bigger than a chief cell

but its nucleus is slightly smaller. Its cytoplasm is intensely eosinophilic because of the presence

of many acidophilic granules. Electron micrographs show that these granules are actually

mitochondria with numerous cristae. Oxyphil cells are generally nonsecretory although some

synthesize minimal amounts of parathormone.

 They are suspected to be chief cells that are in a different physiological state. This assertion is

strengthened by the fact that there are cells in the parathyroid gland (transitional cells) that have

structural characteristics that are in between chief cells and oxyphil cells.
PARATHYROID GLAND

 The parathyroid gland secretes only one hormone, the parathyroid hormone, which is

synthesized and secreted by the chief cells.

 The parathyroid hormone is the most important regulator of blood calcium level and its secretion

is controlled by the level of ionized calcium in the blood.

 When the blood calcium level is low, the chief cells produce and secrete parathyroid hormone,

which stimulates the osteoblasts to secrete hormone-like substances that increase the

proliferation and activity of osteoclasts; inhibits the bone formation activity of osteoblasts;

enhances calcium reabsorption in the renal tubules; increases the conversion of vitamin D to its

active form; increases the excretion of phosphate by the kidneys; and promotes the absorption

of calcium in the digestive tract.

 High level of blood calcium, on the other hand, suppresses the activity of the chief cells, causing

calcium to be deposited in bone.

ADRENAL GLAND

 The paired adrenal glands (left and right) are flat, pyramidal organs that rest on the upper pole

of each kidney

 The adrenal gland presents an indentation (hilus) at the middle of its anteromedial aspect. This is

where the adrenal vein leaves the gland. The adrenal arteries enter the gland through its capsule.

 The stroma of the adrenal gland consists of a relatively thick connective tissue capsule and

elements from this capsule (mostly reticular fibers and cells) that penetrate the gland. The

parenchyma of the gland, on the other hand, consists of epithelial cells that are mostly secretory

in nature.

 An examination of a coronal section of the adrenal gland shows that the gland consists of two

regions: cortex and medulla.

 The cortex lies immediately beneath the capsule. It completely surrounds the medulla, which

occupies the inner area of the gland.

  The adrenal gland à actually be considered as consisting of two separate endocrine glands

because the cortex differs from the medulla, embryologically, structurally, and functionally.

DEVELOPMENT OF THE ADRENAL GLAND

 The cortex of the adrenal gland is mesodermal in origin while the medulla is ectodermal.

 The cortex is derived from mesothelial cells of the peritoneum that are adjacent to the developing

kidneys. These cells differentiate to form the primitive adrenal cortex. Later, another group of

mesothelial cells, which are smaller than those in the primitive adrenal cortex, invades the area

of the developing adrenal gland and surrounds the primitive adrenal cortex.

 These cells will comprise the definitive adrenal cortex. During the first postnatal month of life, the

primitive adrenal cortex rapidly regresses and its cells replaced by the cells of the definitive cortex,

but only at puberty is the structure of the adult adrenal cortex achieved.

 The medulla, on the other hand, is derived from neural crest cells that form the sympathetic

system. These cells migrate to, and invade the central area of the developing adrenal cortex where

they later get entrapped by the cortical cells.

ADRENAL GLAND: ADRENAL CORTEX

 The cortex comprises 80% to 90% of the adrenal gland. It is essential to life.

 Its function is to produce steroid hormones, collectively referred to as adrenocortical hormones,

which play vital roles in the body's metabolic activities.

 Steroid hormones are small lipid-soluble molecules hence they diffuse freely from cells through

the plasmalemma. Consequently, the secretory cells of the adrenal cortex do not exhibit

cytoplasmic secretory granules.

 The adrenocortical hormones are categorized into three classes (e.g., mineralocorticoids,

glucocorticoids, and androgens). Many hormones comprise each class, but most are secreted in

physiologically insignificant amounts. The only physiologically important adrenocortical

hormones are the mineralocorticoid aldosterone; the glucocorticoids cortisol and corticosterone;

and the androgens dehydroepiandrosterone (DHEA) and androstenedione. The adrenal cortex,

when seen under LM, consists of three concentric zones or layers that are distinguishable by the

arrangement and appearance of their parenchymal cells. From the outside going inwards, these

layers are the a) zona glomerulosa; b) zona fasciculata; and, c) zona reticularis.
ADRENAL GLAND: ADRENAL MEDULLA

 The medulla comprises 10% to 20% of the adrenal gland. Its central area contains large veins

(medullary veins) that drain the entire gland. Unlike the adrenal cortex, the adrenal medulla is not

essential to life, but its hormones help the individual cope with emergencies.

 The parenchymal cells of the medulla (phaeochromocytes; chromaffin arranged in groups or in

thick cords that are surrounded by cells) are sinusoids and richly supplied with myelinated nerves-

in fact, all the parenchymal cells are associated with endings of preganglionic sympathetic neuron.

 They are polyhedral cells with basophilic cytoplasm that, when compared to the cortical cells in

routine histologic preparations, have a larger and more darkly-staining nucleus. They are called

chromaffin cells because the secretory granules in their basophilic cytoplasm exhibit chromaffin

reaction, i.e., when treated with oxidizing agents like chromate, the catecholamines that they

contain get oxidized and turn brown.

 Scattered among the chromaffin cells are sympathetic neurons (ganglion cells), large cells that are

round or polygonal with prominent nuclei, which are the sources of the myelinated nerves that

are associated with the chromaffin cells.

 The hormones produced by the adrenal medulla are collectively referred to as catecholamines.

They are secreted by the chromaffin cells and include epinephrine (adrenaline), norepinephrine

(noradrenaline), and dopamine, which is also synthesized by nervous tissue.

 About 90% of chromaffin cells secrete epinephrine and about 10% secrete norepinephrine while

the cells that secrete dopamine have not been identified yet.

 The catecholamines have no specific target organs or cells. Their effects are widespread and

involve, practically, all the cells of the body.

 Normally, they are continuously secreted in small quantities. However, during "fight or flight"

situations such as fright, they are released into the bloodstream in large quantities and produce

vasoconstriction, increased blood pressure, changes in heart rate, and elevated blood glucose

levels. These effects facilitate various defensive reactions that are designed to enable the changes

in heart rate, and elevated blood glucose levels. These effects individual to cope with emergency

situations.

 Secretion of the catecholamines is controlled by the preganglionic neurons of the sympathetic

nervous system.
  The chromaffin cells are thus essentially sympathetic ganglion cells that respond to stimulation

by the preganglionic neurons not by sending nervous impulses but by releasing hormones by

exocytosis and sending these chemical messengers via the bloodstream to effector cells in the

different tissues and organs.

 In addition to catecholamines, the chromaffin cells also synthesize a wide variety of bioactive

amines and peptides.

ADRENAL GLAND: PARAGANGLIA

 The term paraganglia refers to small clusters of chromaffin cells that are found outside the adrenal

medulla.

 They are associated with autonomic ganglia, nerves of the sympathetic nervous system, and the

aorta.

 The chromaffin cells of the paraganglia secrete mainly norepinephrine.

ISLETS OF LANGERHANS (Pancreatic Islets)

 Pancreas is both an exocrine and an endocrine gland.

 Its endocrine part is composed of the islets of Langerhans.

DEVELOPMENT OF THE PANCREAS

 The exocrine and endocrine portions of the pancreas have the same embryonic origin- the

endoderm that lines the duodenum. In the 3rd month of intrauterine life, the cells destined to

form the islets migrate away from the pancreatic ducts, aggregate around capillaries, and

differentiate into islet cells. During the 5th month of fetal life, the cells start producing hormones.
ISLETS OF LANGERHANS (Pancreatic Islets)

 The islets of Langerhans are 100 to 200 micrometer in diameter each.

 In routine histologic preparations, they are seen as consisting of small aggregations of pale-

staining cells that are scattered among the darker-staining cells that belong to the exocrine

portion of the pancreas.

 Each islet consists of 2,000 to 3,000 cells that form a compact mass that is crisscrossed by

fenestrated capillaries and surrounded by a thin layer of reticular tissue.

 There are over a million islets of Langerhans in the pancreas, but account for only 2% of the

volume of the organ.

 They are more numerous in the tail than in the body or head of the organ.

 The cells of the islets of Langerhans are polygonal and are typically polarized toward the

capillaries into which they discharge their secretions. They consist of four distinct cells types: a, b,

d and F-cells. Each cell type secretes a hormone.

HORMONES PRODUCED BY THE ISLETS OF LANGERHANS

 The islets of Langerhans produce four (4) hormones: insulin, glucagon, somatostatin, and

pancreatic polypeptide.

 Insulin is secreted by the B-cells. It is a polypeptide hormone that is involved in numerous

metabolic processes. Insulin affects practically all cells of the body and its effects are varied, very

profound, and complex. The most notable function of insulin is to facilitate entry of glucose, the

chief energy source of cells, into the cytoplasm of cells.

  In addition to its effect on carbohydrate metabolism, it also affects protein and fat metabolism,

the activity of many enzymes, and electrolyte transport.

 The secretion of insulin by the B-cells is regulated mainly by the level of glucose in the blood. High

blood glucose level stimulates its secretion and release. When insulin is released, it diffuses into

cells throughout the body.

ISLETS OF LANGERHANS

 Secretion and release of insulin by the B-cells end when the blood sugar level returns to normal.

Insulin secretion is also partly regulated by the autonomic nervous system and by some of the

hormones secreted by the digestive tract e.g., enteroglucagon, secretin, cholecystokinin, gastrin,

and gastric inhibitory peptide (GIP). Inability of the islets of Langerhans to produce enough

insulin and/or the inability of the body cells to respond appropriately to insulin results in a

disorder called diabetes mellitus.

 Glucagon, which is also a polypeptide hormone, is elaborated and secreted by the a-cells. Like

insulin, the effects of glucagon are varied and complex but its main action is to increase blood

glucose level by ordering the cells of the liver to produce glucose or release it from the organ's

glycogen store.

 Secretion of glucagon by the a-cells is regulated mainly by the glucose level of blood-it is

stimulated and inhibited by low and high blood glucose level, respectively.
 Somatostatin is produced and secreted by the d-cells. Its main action is on the secretion of the

other cells of the islets. It inhibits the secretion of glucagon, insulin and pancreatic polypeptide. It

also minimally diminishes the motility of the stomach, small intestine, and gallbladder. Its release

is stimulated by the increase in blood glucose that occurs after a meal. Somatostatin is also

produced by some cells of the digestive tract and the hypothalamus, but the physiologic effect of

hypothalamic somatostatin differs from that of pancreatic somatostatin.

 Pancreatic polypeptide is produced and secreted by the F-cells. It has been shown to slow down

the absorption of food from the intestines, but its exact physiologic effect is not well-understood

yet. Its secretion is stimulated by low blood level of glucose, a meal containing protein, exercise,

and fasting; it is also partly regulated by the autonomic nervous system.

 The hormones of the islets of Langerhans affect each other. Somatostatin inhibits the secretion

of the three other hormones produced by the islet; insulin inhibits the secretion of glucagon;

while glucagon stimulates the secretion of insulin and somatostatin.