Endocrine Histology

General Features of Endocrine Glands

Endocrine glands can be part of discrete organs (pituitary, thyroid, etc.) or part of another organ (pancreas)

gland cells originate from invaginations of embryonic epithelium into connective tissue

exocrine and endocrine glands form in the same way, but endocrine glands have no ducts

hormone diffuses directly into extracellular space and enters capillaries

Two cell types:

(1) Parenchymal Cells – synthesize and release hormone into bloodstream (in direct contact with capillaries)

polarized polyhedral cells arranged in cords, clumps, or follicles – ER directly abuts basement membrane

peptide-secreting cells have abundant rough ER, Golgi bodies, and secretory vesicles

steroid-secreting cells have abundant smooth ER and mitochondria with tubular cisternae

(2) Stromal Cells – sparse reticular tissue, richly supplied with fenestrated capillaries

Pituitary Gland (a.k.a. Hypophysis = "under brain")

Function – integrates nervous system and endocrine system

receives input from hypothalamus and regulates other endocrine glands

Gross Anatomy –below 3^rd ventricle, median eminence, hypothalamus; over nasopharynx

located in sella turcica (="turkish saddle"), a depression of sphenoid bone

separated from intracranial cavity by a fibrous tissue called diaphragma sellae, a diaphragmatic extension of the dura mater

hypophyseal stalk (infundibular stalk, pituitary stalk) extends through this
the stalk is essential for normal pituitary function

Origin – anterior and posterior pituitary have different lineages

anterior pituitary arises from Rathke’s Pouch (roof of future oral cavity – stomodeal ectoderm)
posterior pituitary arises from floor of diencephalon (neural ectoderm)

Blood Supply – via 2 anastamostic branches of the internal carotid arteries:

(1) Superior Hypophyseal Artery – supplies pars tuberalis, median eminence and infundibular stem

(2) Inferior hypophyseal Artery – primarily supplies the posterior pituitary

unique Portal Blood System within the pituitary – blood from SHA forms a primary plexus of capillaries in the median eminence and stalk of hypothalamus Þ forms loops, the tubular infundibular tract (TIT) Þ drain into hypophyseal portal veins that run along the hypophyseal stalk Þ drain into a secondary capillary plexus in the adenohypophysis Þ thus hypothalamic releasing and inhibiting factors are transported directly to the adenohypophysis and regulate its secretion of hormones Þ blood containing these hormones leaves via hypophyseal veins

blood containing hormones from the entire pituitary leaves via hypophyseal veins into the cavernous sinus

The Pituitary consists of two histologically and functionally distinct parts, Anterior and Posterior.

(I) The Anterior Pituitary = Adenohypophysis – larger than posterior; has a secretory function

The anterior pituitary can be divided into three parts:

(1) pars tuberalis – surrounds pituitary stalk

(2) pars intermedia – separates posterior pituitary (pars nervosa) from anterior pituitary (pars distalis)

of little importance in humans (produces melanocyte stimulating hormone in reptiles and amphibians)
absent in adult except for cysts and undifferentiated colloid-filled cells (not true remnants but landmarks)
has chromophobes and basophils (see below); basophils preferentially invade the pars nervosa of the posterior pituitary

(3) pars distalis – largest and most cellular part, responsible for most of the anterior pituitary’s function

Dense collagenous capsule from which sparse collagen trabeculae that penetrate the gland with blood vessels

Cells are closely associated with vascular sinusoids and are arranged in irregular cords without much connective tissue

Half of the cells in pars distalis are chromophobes (smaller, do not stain well); half are chromophils (secretory cells)

each chromophil cell type secretes its own peptide hormone responsible for regulating another gland
all cell types exist throughout the pars distalis, but proportions vary from region to region – very complicated
chromophil regulation occurs through negative feedback by target organ’s secretion, so removal of target organ leads to hypertrophy of the cells that produce hormone stimulating that organ

Chromophils of the pars distalis (distinguished by staining properties, EM appearance, and immunostaining):

(1) acidophils – 70% of chromophils – smaller than basophils (14-19m m) but larger, coarse granules; significant Golgi

acidophils secrete peptides rather than glycopeptides, so these cells stain PAS negative

acidophils consist of two cell types:

(a) somatotrophs – small cells that secrete somatotropin (growth hormone, GH): (+)GHRH; (-)somatostatin

(b) lactotrophs – widely scattered cells that secrete prolactin (PRL; a.k.a. lactogenic hormone, LTH): (+)PRF’s; (-) dopamine

memory key for acidophils: GPA = Growth hormone and Prolactin are from Acidophils

(2) basophils – 30% of chromophils – larger (15-25m m), finer granules, Golgi further from nucleus

basophils have glycoprotein and stain PAS positive – all hormones they secrete (except ACTH) are glycopeptides
basophils consist of three cell types:

(a) thyrotrophs – large cells that secrete thyroid stimulating hormone (TSH): (+)TRH; (-)somatostatin

(b) gonadotrophs – smaller, secrete follicular stimulating hormone (FSH) and Leutenizing Hormone (LH): (+)GnRH

(c) corticotrophs – most common basophil, secretes adrenocorticotrophic hormone (ACTH): (+)CRF

memory key for basophils: B-FLAT = Basophils produce FSH, LH, ACTH, and TSH

(II) The Posterior Pituitary = Neurohypophysis –stores and releases hormones from the hypothalamus

The posterior pituitary is a nerve tract that stores and releases two octapeptide secretory products:

(1) Oxytocin – stimulates smooth muscle contraction of the uterus and myoepithelial mammary gland cells

(2) Vasopressin (Anti-Diuretic Hormone, ADH) – Ý permeability of distal nephron to increase H₂O reabsorption

These hormones are made in the neuron cell bodies in the hypothalamus (supraoptic and paraventricular nuclei) Þ travel by axoplasmic flow to the neurohypophysis and remain as granules within the axon Þ granules produce axonal swellings called Herring Bodies (the Secretory granules contain hormone, ATP, and hormone-binding/transport protein called neurophysin) Þ released in response to electrical activity of the neurons in the hypothalamus

since it does not produce its own secretions, the posterior pituitary is not a true endocrine gland

there is no blood brain barrier in the pars nervosa

Connective tissue is similar to pars distalis but with few cells; contains true fenestrated capillaries instead of sinusoids

The posterior pituitary can be divided into two parts:

(1) infundibulum = pituitary stalk – connects the pars nervosa to the hypothalamus

Consists of unmyelinated axons of 10⁵ neurosecretory neurons that run parallel to stalk and terminate in pars nervosa

Contains hypothalamo-hypophyseal tract (Tubular Infundibulum Tract, TIT; see Blood Supply, above)

(2) pars nervosa – base of pituitary lobe – major site of hormone release; 3 components to pars nervosa:

(a) unmyelinated nerve fibers

(b) Pituicytes are irregularly shaped glial like cells that are associated with capillaries and may have astrocyte-like function

(c) Herring bodies

Thyroid Gland

Function – produce and secrete thyroid hormone (triiodothyronine- T₃; thyroxine- T₄), and Calcitonin

Gross Anatomy – two lobes (left and right) adherent to sides of trachea; joined by narrow isthmus over anterior trachea

rich blood supply via superior and inferior thyroid arteries; mostly vasomotor innervation

Origin – follicular cells from migration of cells from endodermal floor of pharynx at 2^nd pharyngeal pouch

parafollicular cells from 5^th pharyngeal pouch (a.k.a. ultimobranchial body), mainly to upper thyroid
remnants of connection to oral cavity (thyroglossal duct) may pathologically exist in adult

Histology – vascular connective tissue capsule loosely attached to fibrous connective tissue adherent to the gland

loose connective tissue penetrates as trabeculae dividing the gland into lobes and lobules
reticular network carries rich supply of blood/lymphatic vessels (these collapse during fixation)
the functional unit of the thyroid is the follicle, a spherical cyst-like structure of simple epithelium surrounding colloid

TSH: Ý blood flow to the thyroid, Ý oxygen use by the thyroid, and Ý synthetic activity by the thyroid

There are two cell types in the follicular epithelium:

(1) follicular cells (a.k.a. principal cells) – produce and resorb thyroid hormone

basophilic with central or basal nuclei, many apical mitochondria, and well developed Golgi
fine basement membrane, luminal microvilli, secretory and colloid inclusions within the cell

columnar when actively secreting and squamous when inactive

(2) parafollicular cells (a.k.a. Clear cells or C cells) – lower blood [Ca⁺⁺] via calcitonin (ß osteoclast resorption)

in follicular basal lamina (never reach lumen) with processes to capillaries; stain lightly, vary in shape and size
may be involved in biogenic amine metabolism since secretory granules also contain catecholamines and MAO

Parathyroid Gland – 4 lobes located on posterior surface of thyroid gland

Function – to increase blood [Ca⁺⁺] via parathyroid hormone (parathormone, PTH) which Ý osteoclast activity; Ý Ca absorption from gut; and decreases clearance of Ca while increasing the excretion of PO₄

Structure – separated from thyroid by a thin CT capsule; closely opposed plates of cells – two cell types:

(1) chief cells – smaller but more common of the two, produce PTH (regulated by Ca plasma conc)

(2) oxyphil cells – stain lighter and pinker, have clear walls; unknown function

Adrenal Gland – consists of cortex and medulla

Gross Anatomy – located above kidneys, varies in size with age and health

supplied by three branches of inferior, middle, and superior suprarenal arteries:

(1) capsular arteries – surround the entire gland and drain into capsular veins

(2) terminal branches (cortical arteries) – pass through cortex as sinusoids emptying into medullary veins

glucocorticoid released into these arteries from cortex induces medulla to release epi. rather than norepi.

(3) non-terminal branch (medullary arteries) – penetrates cortex to supply medulla with fresh blood; medulla thus has 2 sources of blood

each of these branches drains into one central vein that runs the length of the gland and emerges at the hilus

muscle at hilus can contract to restrict blood flow and Ý exposure time of ACTH to adrenal cells

preganglionic sympathetic fibers supply the adrenal medulla via greater and lesser splanchnic nerves

(I) Adrenal Cortex – 90% of the adrenal gland, produces steroid hormones

Origin – develops under control of ACTH from the pituitary (ACTH is required to maintain the organ in adulthood too)

fetal cortex forms from mesodermal lining of coelom near cranial end of the mesonephros and root dorsal mesentery
a second invasion of epithelial cells surrounds the fetal cortex and eventually differentiates into adult cortex
in 3^rd and 4^th months of gestation, the fetal adrenal cortex is larger than the kidneys

Histology – covered by dense CT capsule that sends trabeculae with blood vessels into gland parallel to cellular pattern

cells have lipid droplets of steroid precursors (cholesterol) and abundant smooth endoplasmic reticulum

mitochondria are tubular with alveolar branches containing most enzymes for steroid synthesis

The adrenal cortex can be divided into three regions:

(1) zona glomerulosa – acidophilic, dark, small, columnar cells arranged in balls or arcade clusters, some lipid

mineralocorticoids (aldosterone, deoxycorticosterone) – Ý Na⁺ and H₂O resorption in distal convoluted tubule

under negative feedback control by renin-angiotensin system to maintain blood pressure and Na⁺ homeostasis

(2) zona fasciculata – largest zone, also largest cells with large nuclei and polyhedral shape; rich in lipid (spongy)

form parallel cords 1-2 cells thick at right angle to surface surrounded by fenestrated capillaries

glucocorticoids (cortisol, corticosterone) – Ý gluconeogenesis, depress inflammation, alter transcription

(3) zona reticularis – acidophilic cytoplasm with few or no lipid droplets in small polyhedral cells filled with lipofuscin

arranged in irregularly anastamosing cords
2 cell types:

(a) lighter cells (look like zona fasciculata)
(b) darker, more acidophilic with dark shrunken nucleus

sex steroids – act in development and maintenance of sexual organs

(II) Adrenal Medulla – 10% of adrenal gland, produces catecholamines

Origin – from neural crest cells that invade the fetal cortex as it is developing

these are the only neural crest cells that form endocrine tissue – the rest form spinal and sympathetic ganglia
cells receive preganglionic sympathetic innervation via the greater and lesser splanchnic nerves

Histology – characteristic lack of organization; more basophilic than cortex; ganglion cells may be present
There are two cell types in the adrenal medulla:

(1) Chromaffin cell – primary cell type: large, irregular, watery cells arranged in irregular cords close to blood vessels

found wherever sympathetic tissue is located (e.g. paraganglionic masses along the wall of the aorta)
Golgi produces secretory granules that are separated from dense material in the cristernae by a lucent gap
these granules are filled with catacholamines: norepinephrine (more e^- dense) and epinephrine

epinephrine is made from cytoplasmic methylation of norepinephrine that has leaked out of granules
granules (in addition to NE and E), also contain ATP, lipid and protein (e.g. enkephalins)
sympathetic preganglionic nerve stimulation leads to exocytosis of granules and recycling of the vesicle

(2) Ganglion cells – typical large nerve cell: Nissl granules, clear nuclei, distinct nucleoli-satellite and mantle cells;

function is unknown

Pancreas – primarily exocrine organ but has endocrine Islets of Langerhans

Islets of Langerhans – pale staining areas larger than the acini of exocrine pancreas – do not contain ducts

not encapsulated but bound by thin reticular tissue whose fibers penetrate between Islet cells
2 x 10⁵ Islet cells in adult, mostly in tail region

Three distinct cell types are known (no characteristic color or staining):

(1) a cells – secrete glucagon and are located near periphery of Islet

contain large number of red, spherical, membrane-bound glucagon granules that are insoluble in EtOH
granules are more dense in the center of the cell than at the membrane
have many mitochondria and few cisternal profiles of ER; moderately well developed juxtanuclear Golgi

(2) b cells – secrete insulin and are located in the center of the Islet – more numberous than a cells

contain brownish-orange membrane-bound insulin granules that are soluble in EtOH and crystalline in center
large mitochondria and prominent Golgi

(3) d cells – secrete somatostatin – may represent a stage of other Islet cells or transition from acinar to islet cell

contain blue membrane-bound somatostatin granules that resemble zymogen granules of acinar cells