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Structure and Function of Endocrine Organs and Cells
Endocrine Organs
The endocrine system is part of the cellular communication between different cell types and organs. There are
four different pathways of secretion of these messengers to the corresponding target cell.
1. Autocrine secretion: cell secretes messenger that binds to receptors on the same cell, leading to changes in
the cell. An example is local control of cell growth by substance such as interleukin-1.
2. Paracrine secretion: cell secrets messenger that act on adjacent cell. An example is the diffuse
neuroendocrine cells, in intestine and in the respiratory systems.
3. Endocrine secretion: cell secrets messenger to the blood that acts on a distant tissue.
4. Synaptic secretion is when the communication done by direct targeting from one cell to other via synapses.
The endocrine system consists of several endocrine organs as well individual endocrine cells that are located in
various tissues. The endocrine cells are found in three distinct anatomic distributions.
1. They form specialized endocrine organs such as adrenal, aortic and carotid bodies, pituitary, pineal body
parathyroid and thyroid.
2. They form discrete clusters in specialized organs such as pancreas, ovary, and testis.
3. They are dispersed singly among other cells in the intestinal and respiratory systems.
Endocrine cells produce and secret messengers (hormones) into blood to regulate the activity of various cells,
tissues and organs. They are classified into 2 systems, neuroendocrine and endocrine systems that are partially
interconnected and belong to four different classes of molecules. The following list includes examples of some
messengers and the sites of their secretion:
1. Amino acid derivatives adrenalin (epinephrine) and noradrenalin (norepinephrine) secreted by the adrenal
medulla, and thyroxin that is secreted by the thyroid.
2. Small peptides include encephalin of the hypothalamus, thalamus and spinal cord, vasopressin of the
hypothalamus and posterior pituitary.
3. Proteins include nerve growth factor and epidermal growth factor secreted by various cell types and
insulin secreted by Beta-cells of pancreatic islets.
4. Steroids include aldosterone secreted by the adrenal cortex, progesterone and estradiol secreted by the
ovary, and testosterone secreted by the testicles.
Pituitary
Multifunctional organ that consists of 3 different parts: pars nervosa (posterior pituitary), pars intermedia and
pars distalis (anterior pituitary). It is attached to the brain and located beneath the hypothalamus, which controls
hormone production in the anterior pituitary.
Pars distalis (anterior pituitary) contains three cell types that can be identified by H&E staining characteristics.
They are acidophilic, basophilic and chromophobe cells. Functionally, it contains five different cell types
identified through immunohistochemistry:
1. 50% are acidophilic cells that secret GH (somatostain), which acts by stimulating hepatocytes to produce
IGF-1 (insulin-like growth factor-1).
2. 15-20% are acidophilic cells that secret prolactin (PRL), whose major role is to stimulate and maintain post
partum lactation.
3. 15-20% are basophilic cells that secrete ACTH (adrenocorticotrophic hormone), whose primary role is to
stimulate synthesis of GH and steroids in the zona fascicularis and zona reticularis of the adrenal cortex.
4. 10% are basophilic cells that secret FSH (follicular-stimulating hormone) and LH (leuteinzing hormone).
In females, FSH stimulates the development of the ovarian follicles. In males, it stimulates androgen
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synthesis by the sertoli cells. In females, LH stimulates the synthesis of steroids in the ovarian follicles and
the CL. In males, it stimulates the synthesis of testosterone by Leydig cells.
5. ~5% are basophilic cells that secret TSH.
The Pars Intermedia is located between the anterior and posterior pituitary and varies in size and patterning
with species. It is poorly developed and it consists of acini-like glands lined by cuboidal epithelium.
The Pars nervosa (posterior pituitary) contains three components: 1. Neuronal processes with extended axons
from neuroendocrine cells in the hypothalamus. 2. Pituicytes, astrocyte-like cells that support the axons and
fenestrated endothelial cell. The terminal portion of the axons contains secretory vesicles that form dilated axons
(herring bodies) that contain oxytocin or ADH (antidiuretic hormone)/vasopressin. The oxytocin activates the
uterine contraction and milk secretion by the mammary gland. ADH increases the permeability of the renal
collecting tubules to water (produces concentrated urine), as well as arteriolar constriction.
Hypothalamus
Located at the base of the brain and contains several clusters of neurons that secrete 8 different hormones, 2 of
which, oxytocin and ADH, are secreted through its extension in the pars nervosa. The other 6 stimulate or
inhibit the release of hormones by the pars distalis: 1. Thyrotropin-releasing hormone (TRH) 2. Gonadotropinreleasing hormone (GnRH) 3. Growth hormone-releasing hormone (GHRH) 4. Corticotropin-releasing
hormone (CRH) 5. Growth hormone-inhibiting hormone (GIH) 6. Prolactin release-inhibiting hormone (PIH)
.
Pineal Gland
In mammals, it is located in the brain just below the posterior end of the corpus callosum and above the superior
colliculi brain. In reptiles, it is just beneath the skin at the middle of the scull, and therefore called “third eye”. It
contains 2 major cell types: pinealocytes and glial cells. In some species (horses, sheep, goats) they also contain
melanocytes. The pinealocytes are neuron-like cells that secret melatonin (this process is stimulated by
darkness), which induce rhythmic changes in secretion by the hypothalamus, pituitary and gonads, and induce
sleepiness.
Adrenal Glands
There are 2 adrenal glands that are located cranial to the kidney. They consist of two distinct structural and
functional components, adrenal cortex and medulla. The adrenal cortex is yellowish and occupies 80%-90% of
the adrenal gland. It is of mesodermal origin and produces steroid hormones that contribute to its grossly
yellowish color. The medulla is smaller then the cortex, grossly dark in color, and produces catecholamines.
The adrenal cortex consists of 3 concentric zones: 1. Zona glomerulosa is the outer zone (in horse, zona
arcuata), where cells of this zone secret mineralocorticoid hormone and aldosterone that act on the renal distal
tubules. The secretion of aldosterone is under the controls of angiotensin II. 2. Zona fasciculata is the middle
zone that occupies the majority of the cortex. The cells here are large and pale. Like all steroid-secreting cells,
they are rich in sER and contain mitochondria. The cells in this zone secret glucocorticoids that regulate
gluconeogenesis and glycogenesis in different organs (liver, adipose tissue) as well as suppress immune and
inflammatory responses. ACTH controls the production and secretion of glucocorticoids. 3. Zona reticularis is a
thinner zone that contains smaller cells that secret weak androgens (sex hormones).
The adrenal medulla consists of two populations of chromaffin cells (neuroendocrine cells that stain bluish
with H&E) that produce catecholamines. The catecholamines are secreted into the blood and target receptors in
blood vessels walls. On gross section the medulla is intensely brown because of its higher concentration of
catecholamines. In addition, the medulla has myelinated and unmyelinated nerve fibers, ganglion cells, and
vascular channels. The majority the chromaffin cells secrete epinephrine (have an enzyme PNMT that allows
this). Fewer secrete norepinephrine (NE). Species variance account for differences in the ratio between these
two cells populations (alpaca and llama have more NE). One could use immunohistochemistry and electron
microscopy to distinguish between these cell types. Like in other neuroendocrine cells, the ultrastructure of the
secretory vesicles contains electron-dense material.
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Thyroids glands
There are 2 thyroid lobes (in some species, they are connected by an isthmus) that are located on either side of
the upper trachea. The thyroid has 2 different endocrine cell types, one secreting thyroxin (tetraiodothyronin T4,
triodothyronin T3) and one secreting calcitonin. Thyroxin plays a major role in the regulation of the basal
metabolic rate, while calcitonin is involved in calcium homeostasis.
The thyroxin-secreting cells form thyroid follicles. They are columnar cells with large apical pseudopodia and
microvilli that are attached to basal lamina that surrounded the follicles. The follicle space is filled with
eosinophilic material, colloid that consists of T4 and T3. These hormones are assembled from thyroglobulin and
iodine. Low blood level of thyroxin stimulates the hypothalamus to produce and secret thyrotropin-releasing
hormone (TRH), which stimulates the anterior pituitary to secrete thyroid-stimulating-hormone (TSH), which
stimulates synthesis of thyroglobulin by the thyroid gland and secretion of T4 and T3 to the blood.
The parafollicular cells (C-cells) are located in the periphery of the follicular cells. They represent about 0.1% of
the mass of the thyroid tissue and produce calcitonin. The main function of calcitonin is to antagonize the effect
of parathyroid hormone by suppressing calcium mobilization from osteoclasts. Thus, calcitonin secretion is
stimulated by an increase in blood calcium (hypercalcemia).
Parathyroid glands
There are 4 small parathyroid glands that are closely associated with the thyroid gland and arranged in pairs.
They consists of 2 cell populations, principle cells and oxyphil cells. Principle cells (chief cells) are the majority
and are responsible for the secretion of parathyroid hormone (PTH), which regulates the levels of calcium and
phosphate by influencing activities of the bones, kidneys, and intestines. Low levels of blood calcium stimulate
the secretion of PTH. PTH stimulates bone resorption by activating osteoclasts, which leads to osteolysis and
release of calcium and phosphate to the extracellular fluid. It stimulates the kidneys to activate vitamin D3,
which increases the intestinal absorption of calcium. PTH stimulates the renal tubules to reabsorb calcium and
increase urinary excretion of phosphate. Oxyphil cells are fewer, larger and currently not known to have a
secretory role. The cytoplasm of oxyphil cells is eosinophilic and contains large numbers of mitochondria.
Paraganglia
The paraganglia are specialized neuroendocrine glands that are associated with the autonomic nervous system.
The aortic and carotid bodies are the largest paraganglia. They are clusters of neuroendocrine cells in the thorax
and neck that are associated with sympathetic nerves. They act as chemoreceptors monitoring the arterial
oxygen tension and the pH of the blood. They secrete many catecholamines (NE, neurotensin, seratonin, DA).
Clusters of endocrine cells in specialized organs
Pancreas
The pancreas contains islets, islets of Langerhans, which account for 2% of the pancreatic mass. They consist of
4 different endocrine cells: alpha, beta, delta and F cells that each secret a single hormone. Alpha cells (1520%) produce glucagon. Beta cells (70-80%) produce insulin. Delta cells (5-10%) secrete gastrin and
somatostatin. F-cells (2%) produce pancreatic polypeptide. An increase in blood glucose stimulates the secretion
of insulin by beta cells, a process required for the transport of glucose to various cell types (hepatocytes, skeletal
and cardiac muscle, fibroblasts and adipocytes). Glucagon stored in granules is secreted when there is decrease
in plasma glucose levels. Islets also contain both sympathetic and parasympathetic nerves. Parasympathetic
(cholinergic) nerves increase the secretion of both insulin and glucagon. Sympathetic (adrenergic) nerves
stimulate glucagon secretion and inhibit insulin secretion. (In old cats, the replacement of pancreatic islets with
extracellular amyloid leads to an insulin deficiency resulting in diabetes mellitus).
Testicles
The testicles contain large polygonal interstitial cells, Leydig cells, which synthesize testosterone and are
located between the seminiferous tubules. Like all steroid-secreting cells, they are rich in sER and mitochondria.
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Leydig cell function is regulated by two hormones, prolactin and leuteinzing hormone (LH), which are
secreted from the anterior pituitary. Prolactin induces the expression of LH receptors on Leydig cells, which
stimulates the production of testosterone. In embryo, testosterone regulates the differentiation of male internal
and external genitalia. In puberty, testosterone initiates the production of sperm. In the adult, testosterone is
essential for the maintenance of spermatogenesis and the secretory function of sex glands.
Ovaries
The follicular cells of the ovaries contain receptors for two gonadotropin hormones: FSH and LH. During
maturation of the follicle, LH stimulates granulosa cells to secret androgens that are estrogen precursors. FSH
stimulates granulosa cells to convert androgens to estrogen, which stimulates to proliferation of the granulosa
cells. The surge in the release of both FSH and LH in the anterior pituitary occurs ~24 hours before ovulation. In
the absence of fertilization, levels of FSH and LH decreased. If fertilization and implantation occur, the CL of
pregnancy develops, whose function is regulated by FSH and LH. FSH stimulates the production of
progesterone while LH stimulates the production of progesterone and androstenedione (estradiol precursor).
Singly dispersed endocrine cells in the gastrointestinal, respiratory systems, and skin.
Immunohistochemical, histochemical staining and electron microscopy are required for visualization of these
cells. The ultrastructure in these systems contains electron-dense secretory neuroendocrine granules.
Gastroenteroendocrine
The function of the GI tract is regulated by peptide hormones produced by gastroenteroendocrine cells and
neuroendocrine mediators produced by neurons. Gastroenteroendocrine cells have the following functions:
1. Regulate water/electrolyte metabolism and enzyme secretion
2. Regulate the GI motility
3. Stimulate secretion of other peptide hormones.
a. Ghrelin is a hormone produced mainly in the stomach and stimulates appetite.
b. Secretin is secreted in the duodenum and released when pH is <4.5. It stimulates pancreatic
bicarbonate and fluid secretion, and with acetylcholine stimulates chief cells to secrete pepsinogen.
c. G cells located in the pyloric antrum and duodenum produce gastrin. Gastrin stimulates the
production of HCL by gastric parietal cells and initiates gall bladder contraction. A neuroendocrine
mediator gastrin-releasing peptide regulates the release of gastrin, while somatostatin produced by
pancreatic delta cells inhibits its release.
d. Cholecystokinin (CCK) is produced in the duodenum/jejunum; stimulates gall bladder contraction.
e. Gastric inhibitory peptide (GIP) is produced in the duodenum/ jejunum. GIP inhibits gastric
secretion and stimulates insulin secretion when serum glucose levels are high.
f. Motilin is produced in the upper small intestine. It stimulates GI motility. During fasting, it is
released every 90 minutes.
g. Glucagon-like peptide-1 (GLP-1) is produced by cells of the upper small intestine.
Respiratory endocrine
The respiratory endocrine cells are known as bronchial cells of Kultchitsky, which secret hormones and active
peptides including bombesin (gastrin-releasing peptide), calcinon and serotonin. They are present as single
cells as well as small aggregates of neuroendocrine cells called “neuroepithelial bodies”. These bodies are
thought to regulate the airway and vascular caliber.
Skin endocrine
The epidermis, oral mucosa and the buldge region of the hair follicles contain sensory neuroendocrine cells
called Merkel cells. Their distribution over the body surface varies, but they are most abundant in the skin
where sensory perception is acute (fingertips). They are located at the stratum basale and are closely associated
with the terminal bulb of afferent myelinated axons. There are indications that they act as mechanoreceptors,
transducing sensory touch information to associated primary afferent nerve endings.
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