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ENDOCRINE SYSTEM HISTOLOGY

Endocrine histology
Remote communication between cells is mediated by secretion of chemical messengers which activate cells b hi h ti t ll by interacting with specific receptors. Four types of secretion: - paracrine - autocrine - endocrine - synaptic

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Four types of secretion

Four types of secretion for local control of cell growth

Autocrine: cells secrete chemical which acts on its own receptors Paracrine: secretion of chemicals which act on adjacent cells Endocrine secretion: secretion of chemical messengers (hormones) into blood to act on distant tissues Synaptic secretion: direct communication via synapses in nervous system

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Chemical messengers: four main molecule classes

Aminoacid derivatives - ex: epinephrin/adrenalin thyroxine epinephrin/adrenalin, Small peptides - ex: vasopressin, thyroid releasing hormone Proteins - ex: GH, PTH, TSH, EGF, insulin Steroids - ex: cortisol, progesterone, estradiol, testoterone

Endocrine cells
Main role: secrete messenger substances Three distinct anatomic distributions: Gathered together in one specialized organ (ex: adrenal, pituitary and pineal glands) Form discrete clusters in other specialized organs (ex: pancreas, ovary and testis) Dispersed singly among other epithelial tissues esp. gut and respiratory system forming the diffuse neuroendocrine system

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Endocrine cell special characteristics: secretory function

Membrane-bound vesicles: granules containing chemical messenger Secretion by exocytosis Endocrine tissues vascular (rich capillary network): facilitate rapid dissemination of secretions into blood E d i messengers act slowly b Endocrine t l l because th they have to diffuse into bloodstream, circulate to a target organ and enter target cell

Endocrine cell special characteristics: secretory function

Neuroendocrine NE cells secrete amines or peptides p p Metabolic features involving uptake of amines which undergo decarboxylation in the process of hormone synthesis = APUD cells Amine Precursor Uptake and Decarboxylation (term falling into disuse) Chromogranin & synaptophysin: components of granule in NE cells IHC detection: marker of NE differentiation

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Endocrine glands
Pituitary gland or hypophysis - anterior pituitary - posterior pituitary Hypothalamus Pineal gland Thyroid gland Parathyroid glands

Endocrine glands
Adrenal glands - adrenal cortex - adrenal medulla Pancreas Ovary and testis Diffuse endocrine system Paraganglia

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Pituitary gland:
Multifunctional
Secretion of multiple hormones: action on many peripheral endocrine cells Bean-shaped 12x10x9mm gland 0.4-0.9 gm in adult Beneath brain Linked to brain by pituitary stalk Surrounded by bone of base of skull in depression of sphenoid bone: sella turcica

Anterior and posterior pituitary

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Two anatomic parts of pituitary

Anterior pituitary or adenohypophysis - distal lobe: major part - intermediate lobe - tuberal lobe: in pituitary stalk Posterior pituitary or neurohypophysis - neural lobe behind anterior pituitary - pituitary stalk: axons run from brain - median eminence: funnel-shaped extension of hypothalamus

Vascular supply
Blood vessels (pituitary portal system) carries bl d f i blood from h hypothalamus of b i th l f brain, containing both stimulatory and inhibitory hormones, to stimulate or inhibit the hormone secretion of the anterior pituitary Hormone secretions of anterior pituitary diffuse back into capillary network pituitary vein systemic circulation

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Vascular supply of anterior pituitary

Hypothalamic control of anterior pituitary hormone production

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Anterior pituitary:
5 types of endocrine cells
Somatotrophs 50%: secrete growth hormone GH Lactotrophs 25%: secrete prolactin PRL Coricotrophs 15-20%: secrete adrenocorticotropic hormone (ACTH), lipotrophin (-LPH), li t hi ( LPH) -melanocyte l t stimulating hormone (-MSH), and endorphin

Anterior pituitary: 5 types of endocrine cells

Thyrotrophs 5% : secrete thyroid stimulating hormone (TSH) Gonadotrophs 5% : secrete gonadotropic hormones, follicle stimulating hormone (FSH), and luteinizing hormone (LH) EM: difference in size, shape and electron-density of the core granules

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Distribution of anterior pituitary cells: PRL, FSH, LH scattered thru gland

Methods for demonstrating cells of the anterior pituitary

Traditional method: histochemical staining pattern Electron microscopy EM: electron-dense granules in cytoplasm Immunohistochemical classification IHC according to hormone content using antibodies to each hormone type (nowadays used; best method)

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Traditional method: three types of cells

Chromophils - Acidophils - Basophils Chromophobes

Traditional method: types of cells

Acidophils: cytoplasm staining with acidic dyes (GH PRL) d (GH, Basophils: cytoplasm staining with basic dyes and PAS (TSH, ACTH, FSH, LH) Chromophobes: cells with no cytoplasmic staining because few granules (may be PRL, GH, TSH or ACTH)

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Anterior pituitary H&E

Modified Azan: Basophil and Acidophil and Chromophobe

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EM: hormone-containing electrondense granules

IHC/ ant. pituitary: ACTH cells

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Ant. Pituitary: IHC FSH cells

Posterior pituitary
Continuation of the hypothalamic region of brain: Extends down into pituitary stalk and sella turcica Secretion of oxytocin and antidiuretic hormone (ADH or vasopressin) Composed of axons of neuronal cells lying in l i i supraoptic and paraventricular ti d ti l nuclei of hypothalamus + supporting glial cells = pituicytes

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Posterior pituitary: axons of neurons & pituicytes(stellate specialized glial cells)

Post. pituitary: nonmyelinated axons of neurosecretory cells & pituicytes

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IHC neurofilament + axons

Hypothalamic control of pituitary

Connection to anterior pituitary by pituitary portal vessels ( d i h t l l (endocrine hormones) ) Connection to posterior pituitary by pituitary stalk

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Pineal gland
Below posterior end of corpus callosum Cone-like 6-10mm long and 5-6mm wide Covered by leptomeninges Composed of lobules of specialized cells, separated by septa containing unmyelinated nerves and blood vessels

Pineal gland

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Pineal gland: two cell types

Pinealocytes: neuron-like cells producing melatonin l t i rythmic changes i th i h in secretions of hypothalamus, pituitary and gonads Rosettes of cells with pink staining cytoplasm surrounding fibrillary processes Glial cells : bipolar elongated cells between nests of pinealocytes

Pineal gland: pinealocytes/ clusters of modified neurons + neuroglial cells + capillaries + pineal sand

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Pinealocyte cell bodies + background pink-staining cell processes

Thyroid gland
Two lateral lobes: on anterior portion of neck, on either side of th id cartilage k ith id f thyroid til and upper trachea Isthmus joining both lobes Weight = 15 20 gm 15-20 Thin capsule septa separating the lobules

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Thyroid gland
Two hormones Thyroxine: regulation of basal metabolic rate Calcitonin: calcium homeostasis

Thyroid gland
Acini: single layer of specialized thyroid follicular ith li l ll forming ti htl f lli l epithelial cells f i tightly packed spherical units Lumen filled with colloid = pink-staining homogeneous proteinaceous material rich in thyroglobulin Basement membrane

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Thyroid acini and colloid

Thyroid acini and thyroid epithelium

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Thyroid hormones: thyroxine

Two thyroid hormones: iodinated derivatives of tyrosine ft i T3 triiodothyronine T4 tetraiodothyronine or thyroxine: main form produced by thyroid follicular cells Thyroglobulin: storage form of thyroxine Thyroglobulin: iodinated glycoprotein

Thyroid gland
Low blood thyroxine stimulate hypothalamus t produce th t i h th l to d thyrotropin releasing hormone (TRH) stimulation of anterior pituitary to produce TSH stimulation of synthesis and breakdown of thyroglobulin increase thyroxine level in circulation

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Thyroid gland
Thyroid gland unique: large amount of hormone stored i th extracellular h t d in the t ll l compartment While in other glands, small amount stored intracellular compartment

Thyroid hormones: calcitonin

Calcitonin-producing cells (C cells): scattered between the thyroid follicle cells + small interstitial clusters Pale cells difficult to see on routine stains Visualized either by EM or immunohistochemistry

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Thyroid hormones: calcitonin

If high blood calcium level C cells secrete calcitonin Inhibits calcium resorption from bones by osteoclasts: antagonizing the action of parathormone lowering blood calcium levels

Thyroid C cells: routine H&E

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Thyroid C cells: IHC

Parathyroid gland
Secretion of parathormone involved in calcium homeostasis At least four; In some people, up to eight Small, coffee-colored ovoid glands 5mm long, 3mm wide, 1-2mm thick 130 mg in adults In neck, thyroid region Rarely, intrathyroid or in mediastinum

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Parathyroid gland; thyroid region

Parathyroid: 3 cell types

Adipocytes: increase in number from puberty to adult age b t t d lt background ti b k d tissue Chief cells or parietal cells producing parathormone Oxyphil cells arranged in nests and cords close to a network of capillary vessels

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Nests of parathyroid oxyphil & chief cells + background adipose tissue

Chief cells and oxyphil cells

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Parathyroid chief cells

Diameter = 8-10 m Spherical Small , round, central nuclei Pale, pinkish-purple cytoplasm If serum calcium low, chief cell increase in number hyperplasia

Parathyroid oxyphil cells

Larger than chief cells Abundant eosinophilic granular cytoplasm: abundance of mitochondria Increase in number in elderly patients

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Parathyroid chief cell & oxyphil cell

ADRENAL GLAND
Located on the upper poles of the kidneys Two distinct endocrine systems within one T di ti t d i t ithi organ: Adrenal cortex or outer layer: secretion of steroid hormones from cholesterol Adrenal medulla or central part of gland: neuroendocrine component synthesizing and secreting vasoactive amines: epinephrine and norepinephrine

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Adrenal cortex and medulla Outer capsule

Adrenal cortex: 3 distinct zones

Zona glomerulosa (narrow outer, subcapsular zone): synthesis and secretion of mineralocorticosteroids; mainly aldosterone and deoxycorticosterone Zona fasciculata (midzone widest zone): glucocorticoids; mainly cortisol Zona reticularis (innermost; thickness intermediate between both): androgenic steroids and glucocorticoids

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Adrenal cortex: 3 zones

Adrenal cortex zona glomerulosa: small compact cells

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Adrenal cortex: zona fasciculata; columns of lipid-rich cells + cap

Adrenal cortex: zona reticularis

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Adrenal medulla
Center of adrenal gland Part of neuroendocrine system: secretion of epinephrine and norepinephrine Clumps, cords and columns of large cells separated by a rich network of capillaries EM: neuroendocrine granules impart the basophilic cytoplasmic granularity on light microscope

Adrenal medulla

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Adrenal medulla; large nucleus & finely granular cytoplasm

Adrenal medulla EM: dense-core granules

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Adrenal gland
Adrenal cortex - aldosterone secretion is controlled by renin-angiotensin system - cortisol secretion under the control of pituitary hormone ACTH Adrenal medulla: controlled by sympathetic nervous system

PANCREAS
Three forms of neuroendocrine component of pancreas: f Islets of Langerhans distinct structures: most of hormone-producing cells Isolated nests of neuroendocrine cells forming small groups Single cells scattered within exocrine and ductular component of pancreas

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Pancreas: islet of Langerhans

Spherical clusters of pancreatic endocrine cells embedded i exocrine component ll b dd d in i t Islets smaller and paler than exocrine component Capillary network in contact with each cell: fenestrated endothelium Each cell type identified by its main hormone

Pancreas: islet of Langerhans

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Pancreas: islet of Langerhans

Pancreatic islet
Each islet contains a number of different neuroendocrine cells d i ll Each cell type is identified by its main hormone Four main cell types and at least two minor types

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Four main types of pancreatic endocrine cells

Insulin-secreting cells (B or cells) 70% Glucagon-secreting cells (A or cells) 20% Somatostatin-secreting cells (D or cells) 5-10% Pancreatic polypeptide secreting cells (PP cells) 1-2 %

Insulin-secreting cells : IHC

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Glucagon-secreting cells : IHC

Minor cell types

Vasoactive-intestinal peptide (VIP)secreting cells ti ll Mixed secretion cells (EC or enterochromaffin cells)

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Diffuse neuroendocrine system

Extensive system of scattered neuroendocrine cells producing hormones Action on local environment, but also distant systemic APUD cells : amine precursor uptake and ll i t k d decarboxylation & characteristic cytoplasmic organelles known as densecore granules or neurosecretory vesicles

Diffuse neuroendocrine system

Gut-associated endocrine cells seen throughout the intestinal t t th h t th i t ti l tract Respiratory-associated endocrine cells seen throughout the respiratory tract

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Gut-associated endocrine cells

Enteroendocrine cells concentrated in stomach and small i t ti t h d ll intestine Small, spherical cells, pale staining cytoplasm, difficult to see by routine Best demonstrated by IHC Lying on basement membrane Many not in contact with lumen

GI NE cell vs Paneth cell

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EM enteroendocrine cell

IHC synaptophysin: glycoprotein specific to NE vesicle membrane

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Respiratory-associated endocrine cells

Individual cells or small aggregates scattered in trachea, intrapulmonary tt d i t h i t l airways and occasionally in alveolar wall Lie on basement membrane Pale staining, difficult to see by H&E Need special techniques to visualize: EM & IHC

Paraganglia
Specialized neuroendocrine glands associated with th autonomic nervous i t d ith the t i system Prominent NE cells containing neurosecretory vesicles Precise function mechanism of action and function, nature of secretions is not clear

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Extra-adrenal portion of paraganglion system

Paraganglia
Large paraganglia in thorax and neck ex: aortic body (aortic pulmonary paraganglia at aortic arch) and carotid body (bifurcation of external and internal carotid arteries) chemoreceptors: monitor O2 tension p and pH of blood

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Paraganglia
Vary in size from clumps a few cells associated with nerves, visible only under i t d ith i ibl l d the microscope, to anatomically distinct structures up to 3mm in diameter

Paraganglia
Chief cells: NE cells with neurosecretory vesicles arranged i nests ( ll b ll ) i l d in t (zellerballen) / pale or dark cells Sustentacular cells: occasional flattened support cells at periphery of clumps of NE cells with cytoplasmic processes Blood vessels: network of capillaries with fenestrated endothelium

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Paraganglion: clumps of chief cells

Small aortic paraganglion: NE cells

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