Endocrine Organs & Tissues

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.

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.

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.

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 hypothalamus-hypophyseal 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).

Adrenal (Suprarenal) Glando 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.

characteristic;cell type

hormone secreted

hormonestructure

secretioncontrolled by

target controlled

(gland, process)

basophil; gonadotrope

FSH: folliclestimulatinghormone;

LH: leutinizing hormone

glycoprotein;

glycoprotein

GnRH:gonadotropin-

releasing hormone

ovarian follicles

Leydig cells (spermatogenesis)

basophil;thyrotrope

TSH:thyrotropin

glycoprotein TRH: thyrotropin-releasing hormone

thyroid

basophil; corticotrope

ACTH:corticotropin

polypeptide CRH: corticotropin-releasing hormone

adrenal cortex

acidophil;somatotrope

somatotropin simpleprotein

SRH: somatotropin releasing hormone

growth of long bones

acidophil;mammotrope

prolactin simple protein

PRH: prolactin releasing hormone

secretion of milk

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.

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 TSH-stimulated endocytosis of iodinated thyrogloblin.

Lysosomal enzymes degrade iodothyroglobulin to release T3 and T4 via amino acid channels in basolateral plasma membrane.

hormone produced

(principal one)target secretory

granuleslipid

dropletsSmooth

ERRough

ER

GLOMERULOSAmineralocorticoids

(aldosterone) kidney no yes abundant scarce

FASCICULATAglucocorticoids

(cortisol) liver no yes abundant scarce

RETICULARISgonadocorticoids

(androgens)male

sex glands no yes abundant scarce

MEDULLAepinephrine,

norepinephrinenerve endings,

tissues yes no scarce abundant

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.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.