THE ENDOCRINE
SYSTEM
• The endocrine system consists of all structures of the secretory and hormonal systems.
• Secreted hormones provide the medium for the exchange of information between systems.
• This is accomplished by ensuring the regulation of physiologic functions in conjunction with the
nervous system. That is; the hormonal system
functions in harmony with the nervous system
•This system takes its origin from glands that have lost their
relationship with their epithelial
precursors
These ductless glands secrete their hormones directly into the
bloodstream or lymphatic system;
hence their being referred to as
ductless or internal secretory
glands.
This system is comprised of,
•organs that function as internal secretors,
•cell groups that produce internal secretions
from other systems.
Other endocrine cell groups found in other organs include;
• Islets of Langerhans in pancreas
• Leydig cells in
testis
• Follicles, corpus luteum and interstitial cells of the ovaries,
• The chorionic epithelium in the placenta,
• The enteroendocrine cells of the mucosa and submucosa of the
stomach and bowels.
• Whether they originate from an organ or group of cells, endocrine glands secrete special substances referred to as hormones.
• Hormones secreted from endocrine glands enter directly into the bloodstream or lymphatic system within which they are transported to distant target cells where they exert their effects by adhering to their surfaces.
• Until secreted hormones remain within the glands or cells
that produce them.
The thyroid and ovaries differ in that they store their hormones in special follicles.
Some tissue hormones of peptide or amine structure (parathormone), in addition to
being secreted directly into the bloodstream, can also be secreted into the tissue spaces
found in connective tissues where they
directly (paracrine secretion) affect adjacent
cells.
•Eg; gastrin, secretin, and somatostatin are synthesized in special cells with
paracrine actions on adjacent local cells by way of local diffusion.
•Somatostatin is synthesized by the D cells of the pancreas. It has a
suppressive effect on the enzyme
secretion of the pancreas. They have
been reported to also secrete Gastrin.
•Gastrin secreted from the G cells of the
stomach leads to the release of HCl from
the parietal cells and pepsinogen from the
principal cells.
Also, some cells contain receptors for the hormones they produce.
This hormonal action known as
autocrine control is the means by which these cells regulate their secretory
functions.
Eg; effect of Somatostatin on the cells
that produce it.
•There is also an INTERACRINE EFFECT.
This is the process where the hormone produced exerts its effect within the cell without having to be excreted. Eg;
various growth factors like the growth hormone are also referred to as
interacrine due to their intracellular
effects.
•Hormones exert their effects by
interacting with the receptors found
within or on the target cells. The response elicited depends upon the genetic
program. Accordingly, the same hormone may have different effects on various
tissues.
•To exert its effect only little amounts of
hormone is required.
•Epithelial cells form the functional units of endocrine or secretory glands. These cells have no direct or indirect
relationship with the superficial epithelial
cells.
THE HYPOPHYSIS
(THE PITUITARY GLAND)
• Only a few organs in the body are as small yet important.
• It functions as a regulator of the entire endocrine system.
As a result of the effects of hormones on the sexual organs important events such as
• Sexual maturation,
• Cyclic genital changes,
• Pregnancy and lactation take place.
The hypophysis is also of prime importance in the growth and metabolism of the individual.
• The hypophysis consists of two distinct parts according to its structure and origin:
• adenohypophysis
• neurohypophysis
ADENOHYPOPHYSIS: Rich in cellularity and made up of heterochromatic cells
• Has three parts:
• pars anterior (p. distalis)
• pars tuberalis
• pars intermedia
1- Pars anterior (pars distalis)
• This is the largest part of the adenohypophysis. It is made up of round and cord-like cell groups with abundantly wide capillaries (sinusoids).
Cells belonging to the mononuclear phagocytic system are found in the walls of the sinusoids. The main function of this mononuclear phagocytic system is phagocytosis of antigens, foreign particles microorganisms and macromolecules.
The capsule surrounding the organ sends prolongations into the internal parts.
There are very thin reticular connective tissue surrounding the secretory cells.
• Cells of the pars anterior have varying types and their secretions are different properties.
• Special hormones that regulate the secretion of other endocrine glands (glandotropic hormones) are secreted from here.
Thyrotropic hormone (thyroid stimulating hormone-TSH) stimulates the synthesis and secretion of thyroid hormones.
Thyroid hormone level up to a certain limit when present in the blood leads to suppression of the production of TSH from the hypophysis.
By this, the level of hormone present in the
circulation is held at a stable level. This
mechanism known as negative feedback
bears similarity with the thermostat.
•Adrenocorticotropic hormone (ACTH) is
responsible for development and secretion
from the adrenal cortex.
Follicle Stimulating Hormone (FSH) is
responsible for the development of ovarian follicles, and the seminiferous tubules in the testis as well as the initiation of
spermatogenesis. Together with LH, this
hormone is referred to as gonadotropins
because they control gonadal functions.
•Luteinizing hormone (LH) has as its target organs;
The Leydig cells of testis in males and ovarian
cells in females
The Leydig cells in the testis induce the secretion of testosterone which controls the development of secondary sexual characters (libido, deepening of the voice, and the growth of horns, and growth of the beard) as well as the maturation of the
sperms.
In females, it induces ovulation and formation of
the corpus luteum.
• Apart from its effect on other endocrine glands, the frontal lobe of the hypophysis also acts as an incretoric organ.
• By this, it secretes hormones that directly affect non- endocrine tissues.
• Example:
• Somatotropic hormone (STH) that influence the development and growth of the body,
• Prolactin (LTH or luteomammatropic hormone) is control milk production.
• Cells of the frontal hypophyseal lobe are divided into two groups based on their staining properties:
• Chromophobic cells
• Chromophilic cells
a) Chromophobic cells:
• These, due to their neutrophilic properties fail to absorb dyes and therefore appear as cells with clear cytoplasm under the light microscope.
• Most of these are
considered stem cells that will later differentiate into various cell types.
• A quarter of the stem cells being G cells secrete the adrenocorticotropic
hormone (ACTH).
b) Chromophilic cells:
• These;
• Acidophilic cells that stain with acidic dyes as (A and E cells),
• basophilic cells that stain with basic dyes as (B and D cells).
Acidophilic cells far outnumber their basophilic counterparts.
Both types of cells are round and acidophilic cells appearing to have bigger granules.
The acidophilic and basophilic cells are in close contact with the
walls of the sinusoids; only the basal membrane lies between them.
•The walls of capillaries are especially fenestrated to allow for secreted
materials to easily overcome the
basal membrane barrier to enter the
blood.
• Hormones secreted by the acidophilic cells are in the protein structure.
• Growth hormone-producing (somatotropic hormone -
STH) cells, prolactin or luteomammotropic hormone (LTH) producing cells, and basophilic cells secrete hormones
with glycoprotein structure.
• Thyrotropic hormone (TSH), and gonadotropic hormones (FSH, LH) are also in the protein structure.
2- Pars tuberalis :
• Occupies a very narrow area.
• Its cells contain abundant amounts of glycoprotein which more or less resembles the chromophobic cells but generally do not contain granules. The function of these cells is not known yet.
3- Pars intermedia :
• This is the part of the adenohypophysis that rests on the neurohypophysis as a cord-like narrow segment. In humans, it is generally rudimentary. It is, however, more prominent in domestic animals.
Unlike the pars distalis, this has no acidophilic staining cells. However, it does have numerous basophilic staining cells.
Within the connective tissue are fenestrated capillary vessels.
Cells from this part secrete the hormone (MSH) responsible for the production of melanin in the pigment cells.
•Between the pars intermedia and pars anterior (distalis) lies a
longitudinal space the hypophyseal
cleft; this space, filled with colloid, is
not found in humans and equines.
B- Neurohypophysis: Part rich in nerve fibers
• Neurosecretions produced from the neurons of the hypothalamus are carried along the entire axons where they are stored, to be released when needed.
• This part consists of non-myelinated nerve fibers from the hypothalamus and modified glial cells (Pituicytes).
• Abundant fenestrated capillary vessels can be found between these structures.
Pars infundibularis (infundibulum) the narrow part of the
components of the neurohypophysis and the broader pars proximalis (pars posterior), all represent the same structure.
• The non-myelinated nerve fibers arise from nuclei of the giant cells of the hypothalamus (Nucleus supraopticus and Nucleus paraventricularis).
• Granules secreted from these nuclei (neurosecretory granules), binds to the transporter protein, where they get carried through the neuronal axoplasm (intraxonally) into the proximity of the fenestrated capillary vessels in the neurohypophysis
(neurosecretion).
• Between the fenestrated capillaries and the axonal ends are cells found called pituicytes.
• They cover the axons filled with neurosecretions and bind in a special manner to the fenestrated capillaries
• Neurosecretions are released into the bloodstream by these pituicytes.
•The hormones, oxytocin, and vasopressin are the hormones found in these neurosecretions.
•Oxytocin induces the contraction of the uterine
muscles (during delivery) and that of the alveolar
epithelial cells (Myoepithelial cells) of the mammary
glands (for milk production).
Vasopressin (antidiuretic hormone-ADH) is
responsible for the contraction of muscles within the vessel wall, and together with aldosterone acts especially in the reabsorption of water from the
distal tubules of the kidneys leading to
concentrated urine.
•In situations in which the fluid content of the blood is reduced such as in coma and dehydration, secretion of ADH is
increased.
•In the deficiency of ADH (diabetes
insipitus) develops in which very-low-
density urine is excreted; leading to
drying up of the internal milieu.
•The hypothalamus is connected with the neurohypohysis through the non- myelinated nerve fibers and also with the frontal lobe through the blood vessels.
•The hypophysis together with the hypothalamus are known together as the hypothalamo-hypophyseal system
due to their functional
interrelationship.
The required substances for the release of several releasing and inhibitory hormones from the frontal lobe comes from the
neurons of the hypothalamus:
• Releasing (releasing hormone-RH)
• Inhibitor for Releasing (Releasing inhibiting hormone-RIH
• RH and RIH are formed in the nucleus arcuatus, nucleus ventromedialis and nucleus infundibularis of the
hypothalamus.
• For every glandotrop, there is a special "releasing hormone (RH)" and
• An antagonistic effect eliciting "releasing inhibiting hormone (RIH)".
• Eg; Secretion of TSH is under the control of thyrotropin- releasing hormone (TRH) from the hypothalamus.
•Production and secretion of the hypophyseal hormones is
controlled not only by the RH and
RIH but also by various centers of
the nervous system.
THE EPIPHYSIS
•it is also called corpus pineale.
•It has a neuronal origin with
endocrine activity differing
from other endocrine organs
in that it is dependent on
neuronal innervation.
Its stalk referred to as the Habenula is the means by which the epiphysis is connected to the midbrain (diencephalon); myelinated nerve fibers (sympathetic fibers) enter the organs from here and thereafter lose their myelin sheaths and proceed into the parenchyma where they synapse with pinealocytes. By this, they control the release of melatonin.
They enter the pia mater in layers as an integrated thin connective tissue.
• The pineal gland as an endocrine organ in mammals has two types of cells in the parenchyme.
1.Modified glial cells
2.Pineal cells or pinealocytes
• Modified glial cells are cells of fibrous astrocytic type. The pores that lie between the cellular extensions are filled by pinealocytes.
• Pineal cells or pinealocytes account for approximately 95% of the cellular content of the gland.
• They are irregularly shaped with peripheral processes, and lightly staining large round nuclei.
• Pineal cells make up 95%
• Modified glial cells (astrocytes) 5%
Pineal cells secrete melatonin which regulates sexual behavior in humans and various animal
species. Melatonin is an important hormone of the body. It is required for the functioning of all organs of the endocrine system.
Melatonin inhibits pigment formation in contrast to
the stimulatory effect of (MSH) secreted from the
pars intermedia of the hypophysis
.This organ functions as a biological clock showing a circadian rhythm. Light and
darkness have specific implications on the
release of melatonin from the pineal gland. In general, light suppresses the production of
melatonin while darkness stimulates it.
The amount of light reaching the eye
throughout the day are converted to nervous
impulses by the optic nerves. These are then
relayed to the pineal body.
• The epiphysis which demonstrates an active metabolic function delays sexual development until puberty. In other words, melatonin synthesized in the epiphysis shows an anti- gonadotropic property.
• In young animals with their epiphysis removed early puberty is observed; which is reversed after administration of the epiphyseal extract.
• It regulates the seasonal changes observed in animals that show seasonal reproductive activity.
• In fall and winter months the shorter days and longer nights serve to increase melatonin production. This is reversed in the spring and summer months. With the
decrease in the synthesis of melatonin comes a rise in the gonadotropin-releasing factor secretion. This, in turn,
stimulates further gonadal hormone production leading to
an increase in sexual behaviors.
It also regulates some periodic states of the body;
example it regulates sleep.
It is thought to have a role in determining the sense of direction and activating the immune system.
The Pineal gland is known to contain hydroxyapatite crystals of glial and
stromal origin, which have been
demonstrated to accumulate in the brain as it ages referred to as the
brain sand.
THE THYROID GLAND GLANDULA THYROIDEA
Originates from the pharyngeal endoderm.
It is an organ that both synthesizes and stores as well.
• Unlike other endocrine glands, the thyroid gland resembles exocrine glands in structure.
• It is surrounded by a fibrous capsule.
Thin connective tissue extensions from the capsule continues into the gland and divides it into incomplete lobules.
Inside these lobules that are in contact with each other are follicles of varying sizes (thyroid follicles).
These follicles which are round, oval or cornered due to pressure from the sides have walls lined with a single layer of epithelial cells.
The luminal side of the follicle epithelial cells is microvilli.
Since epithelial cells synthesize hormones, they have abundant rough ER, free ribosomes and well developed Golgi complex. In addition, numerous vesicles, lysosomes, and mitochondria are found.
• The parenchyma of the thyroid is composed of millions of rounded epithelial structures called thyroid follicles.
• Each follicle consists of a simple epithelium and a central lumen filled with a gelatinous substance called colloid.
The thyroid is the only endocrine gland in which a large quantity of secretory product is stored.
Moreover, the accumulation is outside the cells, in the colloid of the follicles, which is also unusual.
There is sufficient hormone in follicles to supply the body for up to three months with no additional synthesis.
Thyroid colloid contains the large glycoprotein thyroglobulin (660 kDa), the precursor for the active thyroid hormones.
• Between the apical surface of the follicle epithelium and the colloid, vacuoles are seen on a light microscope.
• These are unnatural structures that are formed by shrinkage of the colloid when preparing thyroid tissue for light microscopy. These structures are called marginal vacuoles.
• Colloid, is a homogenous or thin granular structure with affinity more to acidic and less so to basic dyes. It shows different colors based on its degree of maturation.
Iodine found in the extracellular space is bound to the free thyroxin groups in the forms of tri-iodothyronine(T3) and tetra-
iodothyronine(T4) (thyroxine).
When required, the contents of the follicular lumen through the activity of proteolytic enzymes (protease) is hydrolyzed and by pinocytosis re-enters the cells.
• Hormones released into the interstitium from the cell base by exocytosis are carried into the capillaries.
• The capillaries here have a rather large lumen and fenestrated endothelial cells.
As seen here, thyroid follicles have different functions:
-Release of the secretion into the follicular space (extrusion).
-Deposition of colloid or the secretion, and its maturation.
-Reabsorption of the matured colloid, re-processing and release through the basal membrane into the blood.
All these are undertaken, to a large extent, under the effect of TSH released from the hypophysis.
Changes in the general conditions associated with life (temperature
changes, hunger, pregnancy, aging, etc..)
leads to important structural changes in
the thyroids as a result of the changes in
metabolism.
The connective tissue between the thyroid follicles contains larger cells, either individually or in groups. These arise from the crista neuralis and differentiate into larger cells with light-colored cytoplasms.
• These cells generally found outside of the follicular epithelia are referred to as parafollicular cells or C cells.
• Parafollicular cells secrete the calcitonin hormone, which plays a role in calcium metabolism.
• This hormone activates osteoblasts by reducing the amount of calcium in the blood and thus affects bone formation.
THE PARATHYROID GLAND
(GLANDULA PARATHYREOIDEA)
• This organ embedded within the thyroid capsule is made up of several parts.
• The parathyroid also originates from the pharyngeal endoderm.
• A thin layer of connective tissue separetes from capsule, and protrudes into the organ.
• This connective tissue contains blood and lymph vessels as well as nerve fibers.
• Epithelial cells that form the parenchyme are in the form of heaps with the periphery surrounded by reticulum fibers as thin webs.
• The epithelial cells here are of two types:
• Principal (chief) cells
• Oxyphyl cells
•Both types of cells are polygonal.
•Principal (chief) cells are much smaller but larger in number; have small
mitochondria within their cytoplasm,
endoplasmic reticulum, Golgi vesicles, lipid
and glycogen.
•Principal cells (Chief cells) have two types based on staining properties of cytoplasm as pale and dark staining.
•Pale cells are rich in glycogen. These
cells are thought to show different
functional state of dark cells.
Dark staining principal cells secrete the parathormone.
This hormone demonstrates a regulatory effect on calcium metabolism.
With an antagonistic action against Calcitonin, parathormone
increases osteoclast activity leading to increased bone resorption.
Calcium mobilized from increased bone lysis leads to elevation of the serum calcium concentration; concomitantly an increase in phosphate excretion by the kidneys.
• The larger but less number of oxyphyl cells have acidic staining cytoplasm; are seen in very old individuals.
• Oxyphyl cells with small mitochondria and glycogen granules in their cytoplasm have functions still unknown.
ADRENAL GLAND
GLANDULA SUPRARENALIS
• The Adrenal gland is a gland formed by two
tissues of mesodermal and neuroectodermal origin.
• The Cortex develops from the coeliac epithelia
(mesodermal).
• The Medulla develops from the sympathetic aspect of the crista neuralis (ectodermal).
• The organ is surrounded by a fibroelastic capsule externally.
• Connective tissue divisions that extend into the organ from the capsule; are narrow in the cortex but a bit wider in the medulla.
The connective tissue containing large amounts of reticulum fibers are seen as wide lumen and fenestrated capillary
vessels in both the cortex and medulla.
Macrophages are also encountered in these
capillaries.
•Cells that make up the parenchyma constitute as cords or groups in the cortex and medulla.
•In the cortex cellular cords show radial
distribution giving rise to different regions.
In the cortex immediately underneath the capsule is found a very thin area of young cells called the subcapsular blastema.
Formation and regeneration of the cellular cords are done here.
• After birth, with the cessation of the maternal hormonal influence, the adrenal cortex undergoes degradation in the offspring and entire cortex is restructured with originates from the subcapsular blastema.
• The surrounding of the medulla by the cord cells of the cortex in a radial manner has to do with functionality.
• More than fifty hormones from the Adrenal cortex, all without a steroid structure, have been analyzed.
• Cholesterol is required by the cells for hormone synthesis.
• This material is stored in large fat droplets.
• Enzymes required for synthesis are found in smooth ER and mitochondria.
• The mitochondria here are of the tubulous
type. Rough ER and ribosomes are not found
because there is no protein synthesis.
Hormones from the cortex are grouped into three main groups as:
• Glucocorticoids
• Mineralocorticoids
• Androgens
Glucocorticoids:
• Glucocorticoids are required for metabolism of carbohydrate, protein and fat.
• Stimulates gluconeogenesis (synthesis of glucose from non- carbohydrate substrates in the liver).
• Increases protein biosynthesis and burning of fats.
• Glucocorticoids thought to be secreted from all parts of the cortex include;
• cortisone
• hydrocortisone
• Di-hydrocorticosterone
Mineralocorticoids:
• The most prominent of the hormones in this group include aldosterone and desoxycorticosterone.
• Aldosterone is a hormone required for water and electrolyte balance. Its principal effect is demonstrated on sodium. It induces the reabsorption of sodium from the renal tubules
while increasing the excretion of potassium and hydrogen ions in urine. With an increase in the sodium content, there is an increase in the osmotic pressure and consequent increase in water resorption. Thus, water and electrolyte balance is
maintained.
• Desoxycorticosterone affects healing by increasing connective tissue growth in inflammations.
• In situations of inadequate secretion of aldosterone a decrease in sodium, water and chloride reabsorption ensues. A decrease in blood volume and heart beat follows and consequently shock
develops. In excess of aldosterone, an increase in the excretion of potassium from the body ensues leading to a fall in potassium level with the consequence of muscle weakness.
Androgenic Hormones :
•They act on reproductive
organs.
• According to the arrangement of the cords, the cortex is divided into three areas:
• Zona arcuata
• Zona fasiculata
• Zona reticularis
Zona arcuata:
• It is the narrow area immediately underneath the subcapsular blastema.
• This part is so named due to the fact that, except in humans and ruminants, the cellular cord alignment resembles a belt.
In humans and ruminants, however, this cellular cords form a coil and hence the name zona glomerulosa or zona multiformis.
Zona fasiculata:
Is the widest area.
Cellular cords here extending parallel to one another, as columns.
• Cells that form these columns are polygonal; are cells with the most abundant fat
deposits in their cytoplasm compared to all areas of the cortex and appear foamy or honeycombed.
Zona fasiculata:
This is the area with the highest secretion of the Glucocorticoid type of hormones.
However, the same type of hormone are thought to be secreted in other parts of the adrenal
cortex, albeit, in smaller amounts.
Zona fasiculata
:When the hormonal
synthesis is increased (as under stress and times of need) the zona
fasiculata, expands to the disadvantage of its adjacent layers
(progressive change).
In situations of
decreased function, however, the same region regresses (regressive change).
Zona fasiculata:
Zona reticularis:
• It is the region of the cortex adjacent to the medulla.
The cellular arrangement has irregular and they network (reticulum).
The cytoplasm of the cells is stained darker than the
others.
Zona reticularis:
• Cells here contain large amounts of lysosome and phagolysosome lipofuscin and several other pigment materials.
• Cells of the zona reticularis secrete the adrenal
androgen known as
dehydroepiandrosterone.
• This substance, like
testosterone and estradiol, is metabolized to other sex hormones.
• The cortex and medulla border are not regular.
Zona reticularis:
Adrenal medulla
• Chromaffin cells are the main cells here.
• They are of two types based on the size of the chromaffin granules they contain:
• Adrenaline cells
• Noradrenaline cells
Adrenaline containing
cells account for 80% and noradrenaline containing cells account for the
remaining 20%.
Adrenaline containing granules are large and few in number.
Noradrenaline containing granules, on the other hand, are small but numerous.
Between these two types of chromaffin cells lies a single sympathetic
ganglion cell.
• Also, in the medulla, small dark appearing cell
populations that resemble lymphocytic cells under light microscopy are seen.
• These are the undifferentiated
sympatheticoblasts that can differentiate into
paraganglionic cells.
• Chromaffin cells are seen yellow-brown in reaction with chromium salts.
• These cells are round, or web-like and form inter- connecting cords with one another.
• There are enlarged capillaries in the connective tissue between the cords.
• These capillaries open to the large central vein inside the organ.
• The rotation of the central vena is in the capsule direction.
• In the intimal walls of these central veins are found
longitudinal muscle pads.
• Blood flow is regulated by this pads.
• Controlling of the blood flow is functionally very
important.
• Even in very low amounts
adrenaline and noradrenaline is very effective.
THE PARAGANGLION
• Paraganglions are the groups of cells that, originate from the crista neuralis during embryonic development and adopts a glandular character.
• Paraganglial cells turn into gland cells that lose their neural properties and lose their extension.
• These cells synthesize effective substances like adrenaline, noradrenaline, and acetylcholine.
THE PARAGANGLION
• Since all paraganglia cells receive innervation from the
central nervous system, they are kept under control of the vegetative nervous system.
• However, after a certain period of life, they regress or become extinct.
• Adrenal medulla is the largest and most important organ of the paraganglia and remains throughout life.
• Cells in paraganglia secrete substances that are either sympathetic or parasympathetic.
• For this reason, they are also referred to as the sympathetic and parasympathetic paraganglia.
• Cells that secrete substances with adrenergic activity like adrenaline and noradrenaline when dyed after fixation with chrome salts can be demonstrated under light microscopy;
hence they are referred to as chromaffin cells. These belong to the sympathetic group.
• In contrast, cells that do not show chromaffin properties can not be demonstrated by this method of dyeing; these cells containing acetylcholine belong to the parasympathetic group.
THE PARAGANGLION
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