Endocrine Organs & Tissues
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Exocrine glands – secrete onto surfaces continuous with body’s exterior.
Endocrine glands – secrete locally or directly into circulatory system.
o May be incorporated into epithelia – represent diffuse endocrine system (neuroendocrine cels of
lung and enteroendocrine cells of gut).
Pituitary – 2-part gland derived embryologically from 2 different tissues: nervous tissue (neurohypophysis)
and epithelium (adenohypophysis).
o Neurohypophysis is downward outgrowth of brain, while adenohypophysis forms from upwardly
directed pouch of oral ectoderm.
o Neurohypophysis remains attached to brain (hypothalamus) and adenohypophysis loses its
attachment to roof of oral cavity and becomes attached to anterior surface of neurohypophysis.
o Neurohypophysis – stringy-appearing blue tissue.
 Lumen of median eminence is continuous with ventral portion of brain’s 3rd ventricle.
 Median eminence leads to infundibulum of neurohypophysis.
 Narrow extension of infundibulum is stalk of infundibulum, which leads to expanded
terminal swelling, which is pars nervosa of pituitary.
 Pars nervosa – nonglandular appearance.
 No secretory cells and secretory elements are herring bodies, which are enlarged
ends of axons arising from neurons whose cell bodes reside in hypothalamus.
 Supporting cells of posterior pituitary are pituicytes, with oval euchromatic nuclei.
 PAS stain - increased staining surrounding blood vessels that reflects concentration of
hormones near blood vessels which carry away product.
o Adenohypophysis – large more darkly-staining reddish-blue structure, glandular part of pituitary.
 Highly vascularized nature – all of capillaries are sinusoidal capillaries.
 Pars distalis – large very glandular portion.
 PAS stain – cells with PAS-positive granules adjacent t walls of sinusoids ar
gonadotropes and thyrotropes, two of basophils whose hormones are glycoproteins
and stain with PAS.
 Corticotropes represent third types o basophils and compromise about 10% of cells in
pars distalis.
 Between pars distalis and neurohypophysis is pars intermedia, second portion of
adenohypophysis.
 Third portion is pars tuberalis and it is applied to surface of infundibular stalk.
 Branching cords of secretory cells in pars distalis.
 Chromophobes constitute majority of anterior pituitary cells but are not conspicuous
because of their small size and lack of cytoplasmic staining.
 About 30% of chromophils are basophils, and 70% are acidophils.
 Among acidophils, somatotrophs are more numerous (around 50% of all chromatophils).
 Pars intermedia – relatively narrow band of adenohypophysis lcated between pars distalis
and pars nervosa.
 Contains scattered cords of basophilic cells whose secretions appear to be of minor
importance in humans.
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 Cells are more uniformly dark staining than those of pars distalis.
Adrenal gland (Suprarenal gland)
o Two adrenal glands – above R and L kidneys.
o Only a single vein, suprarenal vein, drains each adrenal gland.
o Cortex – consists of 3 layers.
 Outermost zona glomerulosa – thin subcapsular zone composed of small compact cells
arranged in clumps.
 Linear zona fasciculata – composed of large cells (spongiocytes) with finely vacuolated
cytoplasm attributed to accumulated lipid droplets.
 Innermost zona reticularis – composed of cells with eosinophilic cytoplasm arranged in
anastomosing network of cellular cords.
 Prominent capillary network surrounds cells of all 3 zones.
o Medulla – has clear profiles of perfused medullary veins.
 Adrenal medullary cells (chromaffin cells) are larger than cells in adjacent cortex and have
round, pale-staining nuclei and their cytoplasm is usually finely granular and relatively
basophilic.
 One type produces epi ad other type produces norepi.
 These cells usually arranged in clumps r irregular cords and surrounded by rich
network of capillaries.
 Parenchyma cells of medulla are modified sympathetic ganglionic neurons.
 Ach stimulates release of epi/norepi – enter capillaries that drain into large medullary
veins, which are drained by suprarenal veins.
o Relatively thick dense connective tissue capsule envelops the gland.
o Adrenal gland is retroperitoneal – capsule is continuous with subperiosteal adventitia, no serosal
envelope.
Thyroid gland – regulate overall rate of body metabolism.
o Two lobes of thyroid gland are connected across anterior aspect of trachea.
o Parathyroid glands are embedded in thyroid, two per lobe.
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o Has several indistinct lobes, each consisting of many ovoid-to-spheroid multicellular structures of
nonuniform size – thyroid follicles.
o Wall of each follicle consists of follicular cells whose apical surface faces inward and basal surface
faces outward, resting on encircling basement membrane.
 Tight junctions connect these cells.
 In active thyroid gland, follicular cells are low-to tall-cuboidal.
 Inactive thyroid – follicular cells re nearly squamous.
o PAS positive material within follicles – thyroid colloid.
 Consists of thyroglobulin that is produced by thyroid follicular cells and stored within
follicle.
 Bright magenta-stained colloid is not only within follicles proper but also is present in small
phagosomes within apical portions of follicular cells.
 Follicular cells endocytose thyroglobulin that is stored in colloid and produce thyroid
hormone following intracellular lysosomal modification of thyroglobulin.
o Single and grouped parafollicular cells (C-cells) are in walls of follicles and interfollicular spaces.
 Enclosed within basement membrane of follicular epithelium, but do not contact lumen of
follicle.
 Recognized by basally localized granules that stain dark grey with lead-hematoxylin stain.
Parathyroid gland – participates in regulation of calcium and phosphorus metabolism in body.
o Usually 4 parathyroid glands, 2 per lobe of thyroid.
o Reside between posterior surface of posterior surface of thyroid gland and its capsule.
o Morphologically similar to pars distalis of pituitary with its cords of cells intermixed with rich
capillary bed.
o Chief cells (principal cells) predominate in gland and characterized by relatively large nucleus and
by nearly agranular cytoplasm that is notably not especially ample.
o Oxyphil cells – less numerous and typically occur singly or in groups scattered throughout gland.
 Larger than chief cells and have small, dark nuclei with highly eosinophilic cytoplasm
attributable to many mitochondria.
o Delicate parathyroid capsule and reticular interstitial stroma support parathyroid cells.
o Arterial vessels enter gland and then break up into network of fenestrated capillaries that encircle
cells.
Islets of Langherhans – poorly stained endocrine tissue of pancreas.
o Granule-free.
o Each islet is compact mass of epithelial cells supported by fine reticular network containing
numerous fenesterated capillaries.
o Endocrine cells of islets principally secrete insulin, glucagon, and somatostatin.
o α-cells – produce glucagon; 20% of all islet cells.
Enteroendocrine Cells (EEC) – throughout gut, single endocrine cells are scattered among columnar cells
of mucosal epithelium.
o Often known as argentaffin cells or enterochrmaffin cells because of natural affinity for silver or
chromium salts.
o Traditional staining methods permit recognition of several categories of EEC but reveal nothing of
chemical nature of their granules or physiological significance of secretions.
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o Basally located granules are stained with silver stain and so the granules appear black.
o Typically pyramidal in shape with broad base contacting basement membrane.
o Granules are typically clustered in base of cell because that is surface from which they are released.
Parenchyma of gland corresponds to secretory cells; stroma corresponds to connective tissue that
surrounds the secretory cells of gland – contains vessels, capillaries, lymphatics, nerves.
o Fenestrated blood capillaries or sinusoids are very typical in endocrine tissues where they facilitate
access of secreted hormones into blood.
Secretory activity.
o Protein or peptide-based hormones (non-steroid based) are synthesized within RER → hormones are
packaged in secretory vesicles from trans Golgi network and secreted by exocytosis → proteolyric
processing of hormone can continue in vesicle.
 Cells that produce/release non-steroid hormones – extensive RER network, secretory
vesicles.
o Steroid-based hormones are synthesized in mitochondria and SER → freely cross plasma membrane.
 Cells producing steroids don’t contain secretory vesicles, but contain lipid droplets in
cytoplasm.
o Thyroid hormones are synthesized via complex pathway involving biosynthesis of thyroglobulin that
is temporarily stored and subsequently broken down by lysosomal enzymes – hormone is product of
lysosomal digestion.
 Freely crosses plasma membrane (lipophilic).
 Thyroid-producing cells exhibit relatively elaborate RER network and lysosomes, but no
vesicles.
Mode of action of hormones.
o Hormones bind to membrane-bound or intracelullar receptor protein.
o Insulin, GH, prolactin bind to enzyme-linked cell-surface receptor.
 Insulin receptor is transmembrane tyrosine-specific protein kinase → phosphorylation of
IRS-1 → activation of intracellular proteins.
 GH and prolactin bind to enzyme-linked surface receptor associated with a tyrosine kinase.
o TSH, ACTH, LH, PTH, ADH, glucagon, melatonin bind to G-protein coupled receptors → cAMP
→ PKA → phosphorylation of proteins in cell.
o Steroid and thyroid hormones are small hydrophobic molecules that diffuse directly across plasma
membrane f target cells and bind to intracellular receptor protein.
 Water insoluble, persist in blood for hours or days.
Pituitary Gland (hypophysis).
o Pars distalis – composed of cords of parenchymal cells that surround large sinusoidal capillaries
into which they deliver their hormones.
 Chromophils – have affinity for dyes.
 Basophils – granules that stain with basic dyes.
o Corticotrope is most common basophil – produces ACTH; cells have small
clathrin-coated granules that contain precursor POMC.
 Acidophils – granules that stain with acid dyes.
o Most abundant chromophils in pars distalis, and tend to be concentrated
laterally.
 Chromophobes – no affinity for dyes.
 Include nonspecific stem cells of adenohypophysis and degranulated acidophils and
basophils.
o Pars intermedia – basophils synthesize hormones a and b-melanocyte-stimulating hormone (MSH).
o Pars nervosa – no hormones are synthesized within cells.
 Hormones synthesized in neuronal cell bodies in hypothalamus and are transported in
vesicles along axons to reach their final destination in pars nervosa.
 Neuronal processes originating from cell bodies located in hypothalamus travel through
infundibular stalk and terminate on fenestrated capillaries in pars nervosa where hormones
are released.
 Neuroglial cells in neurohypophysis – pituicytes.
 When there’s increased secretion, processes of pituicytes retract, to allow release of
hormone into blood.
 ADH and oxytocin are produced in supraoptic and paraventricular nuclei of hypothalamus –
hormones are nonapeptides bound to carrier glycoproteins and stain with PAS.
 Aggregations of secretory granules – Herring bodies.
o Blood supply – cells of adenohypophysis are activated by releasing factors produced in
hypothalamus and carried to them in blood.
 Blood supply arises from paired arteries originating from internal carotid arteries – branches
of bilateral superior hypophyseal arteries anastomose around median eminence of
hypothalamus and send branches into it to form primary capillary plexus → branches of this
plexus coalesce to form venules that course downward around infundibular process to join
extensive network of sinusoids within pars distalis, secondary capillary plexus.
 Venules connecting primary plexus with secondary plexus constitute hypothalamushypophyseal portal system.
 Additional blood supply is derived from small branches of bilateral inferior hypophyseal
arteries and middle hypophyseal arteries (branches from this ring descend and penetrate pars
nervosa and pars distalis).
staining
characteristic;
cell type
basophil;
gonadotrope
basophil;
thyrotrope
basophil;
corticotrope
acidophil;
somatotrope
acidophil;
mammotrope
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hormone
secreted
hormone
structure
secretion
controlled by
FSH: follicle
stimulating
hormone;
LH: leutinizing
hormone
TSH:
thyrotropin
ACTH:
corticotropin
somatotropin
glycoprotein;
GnRH:
gonadotropinreleasing hormone
prolactin
glycoprotein
glycoprotein
polypeptide
simple
protein
simple
protein
TRH: thyrotropinreleasing hormone
CRH: corticotropinreleasing hormone
SRH: somatotropin
releasing hormone
PRH: prolactin
releasing hormone
target
controlled
(gland, process)
ovarian follicles
Leydig cells
(spermatogenesis)
thyroid
adrenal cortex
growth of long
bones
secretion of milk
Adrenal (Suprarenal) Gland
o Blood supply – adrenals have very high rate of blood flow.
 Medulla has dual blood supply – indirectly via cortical sinusoids and directly via medullary
arteries.
 Medulla receives some blood that has passed through cortex and some that has bypassed
cortical cells.
o Cellular structure and function.
 Gland divided into cortex and medulla, with capsule of connective tissue surrounding it.
 Adrenal cortex is divided into 3 distinct zones:
 Zona glomerulosa – produces aldosterone, which stimulates resorption of Na by
kidney.
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o Release positively regulated by rennin-angiotensin system and negatively by
ANP.
o Atrin opposes contractions of muscle in walls of arteries and inhibits synthesis
and secretion of aldosterone, and inhibits release of rennin from
juxtaglomerular cells, and acts directly on kidney to increase secretin of NA.
o Dopamine is powerful suppressor of aldosterone secretion and serotonin has
stimulating effect.
 Zona fasciculate – cells are vacuolated and referred to as spongiocytes.
o Vacuoles are lipid droplets that contain ester of cholesterol.
o Cholesterol extracted from lipid droplets b cholesterol diesterase and
transported to mitochondria where it’s transformed into pregnenolong.
o Pregnenolone is precursor of aldosterone, cortisol, androgens produced in
adrenal cortex, and it’s produced in cells of zona glomerulosa, fasciculate,
reticularis.
o Mitochondria of steroid-producing cells has internal mitochondrial membrane
in form of tubular cristae.
 Zona reticularis – cells contain lysosomes and lipofuscin (final product of oxidative
degradation of unsaturated membranous FA).
o Cells produce weak androgens (DHEA) that contribute to growth of axillary
and pubic hair in pubertal female but have no significant function in normal
adult individuals.
 Adrenal medulla – modified sympathetic ganglion made up of postganglionic
neurons that lack dendrites and axons.
o Chromaffin cells – arranged in cords closely investing medullary sinusoids
into which they secrete.
 Contain secretory granules containing epi/norepi – epi synthesized
from norepi by PNMT.
Control of adrenal secretion – zona glomeruolsa is mainly under control of rennin
angiotensin system and ANP; zona fasciculate and zona reticularis are under control of
anterior pituitary and ACTH; cells of adrenal medulla under control of sympathetic nervous
system.
hormone
produced
(principal one)
target
secretory
granules
lipid
droplets
Smooth
ER
Rough
ER
GLOMERULOSA
mineralocorticoids
(aldosterone)
kidney
no
yes
abundant
scarce
FASCICULATA
glucocorticoids
(cortisol)
liver
no
yes
abundant
scarce
RETICULARIS
gonadocorticoids
(androgens)
male
sex glands
no
yes
abundant
scarce
MEDULLA
epinephrine,
norepinephrine
nerve endings,
tissues
yes
no
scarce
abundant
Zone
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Thyroid gland.
o Has 2 capsules – external one blending in with visceral and pretracheal layers of deep cervical
fascia, and internal one of connective tissue which penetrates gland and divides it incompletely into
lobules.
o Secretory cells are uniquely arranged into follicles, which include the follicular cells surrounding a
reservoir of colloid, which contains thyroglobulin which, following breakdown in thyroid follicular
cells, becomes thyroid hormones T3 and T4.
o Follicles are separated from one another by loose and highly vascular connective tissue.
o Follicular epithelium is simple epithelium, composed of squamous, low cuboidal or columnar cells.
o Production of thyroid hormones depends on storage of prohormone thyroglobulin in colloid that is
stored within follicles.
 Production of thyroid hormone requires both exocrine and endocrine phases – exocrine
phases involves active uptake of inorganic iodine from blood, synthesis of thyglobulin, and
incorporation of iodine into tyrosyl residues of thyroglobulin by thyroid peroxidase
(iodination of thyroglobulin occurs within follicle); endocrine phase begins with TSHstimulated endocytosis of iodinated thyrogloblin.
 Lysosomal enzymes degrade iodothyroglobulin to release T3 and T4 via amino acid channels
in basolateral plasma membrane.
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o Cellular structure and function of follicular epithelial cells:
 Rest on continuous basement membrane, which separates them from highly vascularized
perivascular spaces.
 Bear short microvilli on free, apical surface.
 Joined to adjacent follicular cells by junctional complexes and gap junctions.
 Extensive RER.
 Golgi apparatus, where product is modified and packaged.
 3 principal types of inclusions: colloid droplets (phagosomes) pinocytosed from luminal
colloid; primary lysosomes; secondary lysosomes (phagolysosomes).
o Thyroid hormomes are derived from tyrosine – TSH produced by basophils in anterior pituitary
regulates production and secretion.
o T3 and T4 provide negative feedback for secretion of TSH by pituitary and secretion of TRH by
hypothalamus.
o Graves disease – autoimmune disease in which antibodies are produced by plasma cells against
TSH receptors on basal surface of thyroid follicular cells – mimic effect of TSH → thyroid gland
hyperfunctional → goiter + exophthalmos.
o Hypothyrodism – can result from autoimmune disease in which antibodies target thyroid peroxidase
and thyroglobulin → destruction of thyroid follicles.
o Parafollicular (C cells) – derived from neural crest cells.
 Usually located in follicular walls, within confines of follicular basement lamia, but are
excluded from contact with follicular lumen by cytoplasmic extensions.
 Large cells, lightly stained by ordinary hematoxylin and eosin but heavily stained by lead
hematoxylin.
 Produce calcitonin, which antagonizes effects of parathyroid hormones – suppresses release
of calcium from bone by osteoclasts and acts to lower serum calcium by causing calcium
uptake by cells and increased calcium deposition in bone.
 Secretion is stimulated by increase in blood levels of calcium.
Parathyroid gland – each posses thin, intrinsic capsule of connective tissue, which separates it from
adjoining thyroid gland; capsule sends trabeculae into parathyroid gland, carrying nerves, vessesl and
lymphatics.
o Cellular structure and function – parenchyma consists of secretory cells arranged in cords, plates and
occasionally follciles, set in loose, highly vascular stroma of reticular connective tissue.
 Principal (chief) cells – central pale nucleus; slightly eosinophilic cytoplasm containing
lipofuscin pigment grains and moderate amounts of glycogen; most numerous cells.
 Oxyphil cells – larger than principal cells with very eosinophilic cytoplasm.
 Appear in gland at about time of puberty and increase in number with age; may
represent transitional chief cells but do not secrete PTH.
o Principal cells produce PTH, which acts in response to low serum calcium levels.
o PTH acts at three target sites: bone (increases bone resorption), kidneys (increases phosphate
exretion and calcium reabsorption), intestine (increases calcium absorption).
Islets of Langerhans – spherical masses of endocrine cells scattered throughout pancreas.
o Separated from rest of pancreatic tissue by reticular fibers.
o Islet composed of cords of cells separate by extensive capillary network.
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o Alpha cells – secrete glucagon, which stimulates glycogenolysis in liver by inducing activation of
liver phosphorylase.
o Beta cells – secrete insulin, stain with aldehyde-fuchsin technique.
 Also contain glutamate decarboxylase.
 Insulin promotes storage of glucose in liver, skeletal muscle, and adipose tissue and promotes
uptake of amino acids by skeletal muscle; increases protein synthesis, accelerates lipid
synthesis, inhibits lypolysis and gluconeogenesis.
o Delta cells – secrete somatostatin; stain with Hellerstrom-Hellman silver technique.
 Somatostatin inhibits somatotropin, thyrotropin, corticotrophin by adenohypophysis.
 Suppresses islet alpha and beta cells.
o F cells – secrete pancreatic polypeptide; recognized with immunocytochemistry and electron
microscopy.
 Pancreatic polypeptide inhibits pancreatic exocrine secretion and causes gall bladder
relaxation and decreased bile secretion.
Diffuse endocrine system – morphological similarities characterize Amine-Precursor Uptake and
Decarboxylation (APUD) cells of thyroid, adrenal medulla, pancreatic islets, lungs, GI.
o APUD cells release amine serotonin and number of peptides such as endorphin, somatostatin, gastin,
secretin, CCK, insulin, glucagon, bombesin.
o Diffuse endocrine cells in lugs are neuroendocrine cells/small granule cells – form aggregates
neuroepithelial bodies.
o Cells in GI – enteroendocrine cells.