OVERVIEW

●​ The endocrine system is composed of several ductless glands, clusters of cells within certain organs, and isolated single
endocrine cells, known as the diffuse neuroendocrine system (DNES) cells, located in the epithelial lining of the
respiratory and gastrointestinal systems
●​ Glands of the endocrine system include the pituitary gland (and a region of the brain known as the hypothalamus), as well
as the thyroid, parathyroid, adrenal, and pineal glands. Additional components of the endocrine system, such as the Islets
of Langerhans, adipose tissue, female gonads, and male gonads, C. Function.
●​ The endocrine system secretes hormones into nearby capillaries and interacts with the nervous system to modulate and
control the body's metabolic activities.
THE PITUITARY GLAND
●​ The pituitary gland lies below the hypothalamus in a bony housing known as the hypophyseal fossa, a depression in the
sella turcica of the sphenoid bone located in the base of the middle cranial fossa of the skull.
●​ The hypothalamus is a region of the diencephalon of the brain; it possesses nuclei that are structurally and functionally
linked to the pituitary gland. The structural link is via a series of axons whose cell bodies are located in the supraoptic and
paraventricular nuclei of the hypothalamus.
○​ These axons form the hypothalamo-hypophyseal tract and terminate in the pars nervosa of the pituitary gland,
where they store and, when needed, release their hormones. The functional connection is via releasing
hormones that are synthesized in the arcuate, paraventricular (and medial paraventricular), periventricular,
ventromedial, and dorsal nuclei of the hypothalamus. These hormones are released by the neurons located in
these nuclei, enter a capillary bed, and make their way, via the hypophyseal portal system to a second capillary
bed in the anterior lobe of the pituitary gland, leave the capillary bed, and bind to their respective target cells in
the anterior pituitary.
●​ The pituitary gland is a relatively small gland, weighing only about 0.6 g in men and 1.2 g in women who are pregnant or
who have given birth to two or more children.
●​ The pituitary is divided into two major subdivisions, the adenohypophysis and the neurohypophysis Each subdivision is
derived from a distinct embryonic analog, which is reflected in its unique cellular constituents and functions.
○​ The adenohypophysis is also called the anterior pituitary gland
■​ It originates from an ectodermal diverticulum of the stomodeum (Rathke pouch).
○​ The adenohypophysis is subdivided into the pars distalis, pars intermedia, and pars tuberalis.
■​ The pars distalis is supported by a connective tissue capsule and framework. It consists of irregular
cords composed of two types of parenchymal cells, chromophils and chromophobes, lying adjacent to
fenestrated capillaries.
■​ a. Chromophils
●​ Chromophils are parenchymal cells that stain intensely because of their
hormone-containing secretory granules. They synthesize, store, and release several
hormones. They are regulated by specific stimulatory and inhibitory hormones produced by
neurons, referred to as neurosecretory cells, in the hypothalamus. These hormones are
conveyed to the pars distalis via a system of portal blood vessels originating in the median
eminence.
●​ Types. Chromophils are classified into two types, acidophils and basophils, depending on
the dyes they bind using special histological stains.
●​ (a) Acidophils
○​ bind acidic dyes and often stain orange or red. They are small cells of two
subtypes: somatotrophs and mammotrophs.
○​ Somatotrophs constitute about 50% of the chromophils and produce
somatotropin (growth hormone). They are stimulated by somatotropin-releasing
hormone and are inhibited by somatostatin.
○​ Mammotrophs (lactotrophs) constitute about 10% of the chromophil population,
except in multiparous women, where they may be as high as 30%. Mammotrophs
produce prolactin, which is stored in small secretory granules. They are
stimulated by prolactin-releasing hormone and thyrotropin-releasing hormone
(TRH) and are inhibited by dopamine (until re-identified that it was designated as
prolactin-inhibiting hormone).
●​ (b) Basophils
○​ bind basic dyes and typically stain blue. They include three subtypes:
corticotrophs, thyrotrophs, and gonadotrophs.
○​ Corticotrophs constitute about 10% of the chromophil population. They produce
pro-opiomelanocortin (POMC) whose by-products are adrenocorticotropic
hormone (ACTH), melanocyte-stimulating hormone (MSH), and lipotropic
 hormone (LTH), a precursor of-endorphin. They are stimulated by
corticotropin-releasing hormone.
○​ Thyrotrophs constitute about 5% of the chromophil population, produce TSH,
and are stimulated by TRH.
○​ Gonadotrophs constitute about 10% of the chromophil population. They produce
FSH and luteinizing hormone (LH) in both sexes, although in men, the latter is
sometimes referred to as interstitial celL stimulating hormone. Gonadotrophs are
stimulated by gonadotropin-releasing hormone, also known as LH-releasing
hormone.
■​ b. Chromophobes
●​ are parenchymal cells that stain poorly.
●​ appear as small cells under the light microscope; the cells lack (or have only a few)
secretory granules and are arranged close to one another in clusters.
●​ sometimes resemble de granulated chromophils in the electron microscope, suggesting
that they may represent different stages in the life cycle of various acidophil and basophil
populations.
●​ may also represent undifferentiated cells that are capable of differentiating into various
types of chromophils.
■​ The pars intermedia
●​ lies between the pars distalis and pars nervosa.
●​ It contains many colloid-containing cysts (Rathke cysts) that are lined by cuboidal cells.
●​ It also possesses basophilic cells, which sometimes extend into the pars nervosa.
●​ These cells secrete the prohormone POMC, which is cleaved to form ACTH, lipotropin, and
MSH.
●​ In humans, MSH acts to induce melanocytes to produce melanin and may act in various
ways to modulate inflammatory responses throughout the body, and it may play a role in
controlling stores of body fat.
■​ The pars tuberalis surrounds the cranial part of the infundibulum (hypophyseal stalk).
●​ It is composed of cuboidal basophilic cells, arranged in cords along an abundant capillary
network.
●​ Its cells may secrete FSH and LH, but this has not been confirmed
○​ The neurohypophysis
■​ is also called the posterior pituitary gland.
■​ It originates from an evagination of the hypothalamus and is divided into the infundibulum, which is
continuous with the hypothalamus, and the pars nervosa, or main body of the neurohypophysis.
■​ Hypothalamo-hypophyseal tract
●​ contains the unmyelinated axons of neurosecretory cells whose cell bodies are located in
the supraoptic and paraventricular nuclei of the hypothalamus.
●​ transports oxytocin and antidiuretic hormone (ADH; vasopressin), each bound to
neurophysin (a binding protein specific for each hormone) to the pars nervosa
●​ Oxytocin binds to neurophysin I, whereas ADH binds to neurophysin II.
●​ contains the distal ends of the hypothalamo-hypophyseal axons and is the site where the
neurosecretory granules in these axons are stored in accumulations known as Herring
bodies.
●​ releases oxytocin and ADH into fenestrated capillaries in response to nerve stimulation.

THYROID GLAND
●​ The thyroid gland is composed of two lobes connected by an isthmus. It is surrounded by a dense irregular collagenous
connective tissue capsule, in which (posteriorly) the parathyroid glands are embedded. The thyroid gland is subdivided by
capsular septa into lobules containing follicles. These septa also serve as conduits for blood vessels, lymphatic vessels,
and nerves.
●​ Thyroid follicles are spherical structures filled with colloid, a viscous gel consisting mostly of iodinated thyroglobulin
●​ Surrounding the colloid within each follicle is a single layer of epithelial cells, called follicular cells. In addition, one or
more parafollicular cells occasionally lie sandwiched between the follicular cells. Both of these parenchymal cell types rest
upon the basal lamina surrounding the follicle, which separates them from the abundant network offenestrated capillaries
in the connective tissue.
○​ Function
■​ Thyroid follicles synthesize, store, and release thyroid hormones.
○​ Follicular cells
■​ Structure
 ●​ Follicular cells are normally cuboidal, but they become columnar when stimulated and
squamous when inactive.
●​ They possess a distended rough endoplasmic reticulum (RER) with many ribosome free
regions, a supranuclear Golgi complex, many lysosomes, and rod-shaped mitochondria.
●​ Follicular cells also contain many small apical vesicles, which are involved in the transport
and release of thyroglobulin and enzymes into the colloid.
●​ They possess short, blunt microvilli that extend into the colloid.
○​ Parafollicular cells are also called clear (C) cells because they stain less intensely than thyroid follicular cells
○​ Parafollicular cells are present singly or in small clusters of cells between the follicular cells and basal lamina.
○​ They synthesize and release calcitonin, a polypeptide hormone, in response to high blood calcium levels.
○​ Calcitonin functions primarily to lower blood calcium levels by inhibiting bone resorption by osteoclasts.

PARATHYROID GLANDS
●​ The parathyroid glands are four small glands that lie on the posterior surface of the thyroid gland, embedded in its
connective tissue capsule.
●​ They have a parenchyma composed of two types of cells, chief cells and oxyphil cells.
●​ They are supported by septa from the capsule, which penetrate each gland and also convey blood vessels into its interior.
●​ They become infiltrated with fat cells in older persons, and the number of oxyphil cells also increases.
○​ Chief cells are small basophilic cells arranged in clusters
■​ Chief cells form anastomosing cords, surrounded by a rich, fenestrated capillary network.
■​ These cells possess a central nucleus, a well-developed Golgi complex, abundant RER, small
mitochondria, glycogen, and secretory granules of variable size.
■​ Function. They synthesize and secrete parathyroid hormone (PTH, or parathormone), which raises
blood calcium levels. High blood calcium levels inhibit the production of PTH. The hormone acts on
osteoclasts and also induces the decrease in calcium excretion by the thick ascending limb of Henle
loop.
○​ Oxyphil cells are large, eosinophilic cells that are present singly or in small clusters within the parenchyma of
the gland
○​ Oxyphil cells possess many large, elongated mitochondria, a poorly developed Golgi complex, and only a
limited amount of RER.
○​ Their function is not known.
○​ PTH functions primarily to increase blood calcium levels by indirectly stimulating osteoclasts to resorb bone. In
concert with calcitonin, the hormone produced and released by the C cells of the thyroid gland, PTH provides a
dual mechanism for regulating blood calcium levels. A near absence of PTH (hypoparathyroidism) may be
caused by accidental surgical removal of the parathyroid glands, which leads to tetany, characterized by
hyperexcitability and spastic skeletal muscle contractions throughout the body.
ADRENAL GLANDS
●​ The adrenal cortex contains parenchymal cells that synthesize and secrete but do not store various steroid hormones.
The production of steroid hormones is dependent on a specific protein, steroidogenic acute regulatory protein (StAR) that
facilitates the transport of cholesterol across the outer membranes of mitochondria.
●​ The adrenal cortex is divided into three concentric histologically recognizable regions: the zona glomerulosa, zona
fasciculata, and zona reticularis
○​ Zona glomerulosa
■​ synthesizes and secretes mineralocorticoids, mostly aldosterone and some deoxycorticosterone.
Hormone production is stimulated by angiotensin II and ACTH.
■​ is composed of small cells arranged in arch-like cords and clusters. These cells have a few small lipid
droplets, an extensive network of smooth endoplasmic reticulum (SER), and mitochondria with
shelf-like cristae.
○​ Zona fasciculata
■​ synthesizes and secretes glucocorticoids, namely cortisol and corticosterone. Hormone production is
stimulated by ACTH
■​ is composed of columns of cells and sinusoidal capillaries oriented perpendicularly to the capsule.
■​ cells contain many lipid droplets and (in tissue sections) appear so vacuolated that they are called
spongiocytes
■​ These cells also possess spherical mitochondria with tubular and vesicular cristae, SER, RER,
lysosomes, and lipofuscin pigment granules.
○​ Zona reticularis
■​ synthesizes and secretes weak androgens (mostly dehydroepiandrosterone and some
androstenedione) and perhaps small amounts of glucocorticoids. Hormone production is stimulated
by ACTH.
 ■​ composed of cells, arranged in anastomosing cords. Many large lipofuscin pigment granules are
common in these cells and are believed to represent lipid-containing residues of lysosomal digestion.
●​ The adrenal medulla is completely invested by the adrenal cortex. It contains two populations of parenchymal cells,
called chromaffin cells, which synthesize, store, and secrete the catecholamines epinephrine (approximately 80% of
chromaffin cells) and norepinephrine (approximately 20% of chromaffin cells). It also contains scattered sympathetic
ganglion cells.
○​ Chromaffin cells are large, polyhedral cells containing secretory granules that stain intensely with chromium
salts (chromaffin reaction).
■​ Chromaffin cells are arranged in short, irregular cords surrounded by an extensive capillary network.
■​ They are innervated by preganglionic sympathetic (cholinergic) fibers, making these cells analogous
in function to postganglionic sympathetic neurons.
■​ They possess a well-developed Golgi complex, isolated regions of RER, and numerous mitochondria.
■​ They also contain large numbers of membrane-bound granules containing one of the
catecholamines, ATP, enkephalins, and chromogranins, which may function as binding proteins for
epinephrine and norepinephrine.
■​ Catecholamine release occurs in response to intense emotional stimuli and is mediated by the
preganglionic sympathetic fibers that innervate the chromaffin cells.