HISTOLOGY FULL-TEXT

William A Beresford MA, D Phil ©
Professor of Anatomy
Anatomy Department, West Virginia University, Morgantown, USA

Chapter 27 ENDOCRINE SYSTEM

A HYPOPHYSIS/PITUITARY GLAND

l General morphology and development
l Linked by a stalk to the base of the brain, and lies surrounded by dural membrane (capsule) in the bony sella turcica.
2 Stalk extends through the dural diaphragma sellae. Pituitary weighs 0.5-l.0 g.
3 Divisions of the pituitary gland
     Primary                      Secondary
                     _
                    |  Pars distalis (anterior lobe)
                    |
Adenohypophysis ----|  Pars intermedia (intermediate lobe)
                    |
                    |_ Pars tuberalis*

                     _
                    |  Pars nervosa/infundibular process (posterior lobe)
                    |                   _
Neurohypophysis ----|                  | infundibular stem*
                    |                  |
                    |_ Infundibulum ---|
                                       |
                                       |_median eminence (of tuber
                                                             cinereum)
  (* together form hypophyseal stalk)

4 Embryological origins

2 Adenohypophysis (histology and function)
l Pars tuberalis - wrapped around the neural stalk are cords of basophilic cells containing gonadotrophic hormones.
2 Pars intermedia - rudimentary in man; variable in width; several colloid-filled cysts; glandular cells - chromophobe or basophil; basophilic cells may extend into the neural lobe; function - unknown in man, but in fish and amphibia the melanocyte stimulating hormone (MSH) formed varies skin pigmentation.

3 Pars distalis

3 Neurohypophysis
May be viewed as a downward extension of the hypothalamus, allowing for hormone storage and a complete breach of the blood-brain barrier for hormone release. Its structure follows:
l The neural stalk and posterior lobe consist of the unmyelinated axons (grouped as the hypothalamo-hypophyseal tract)
2 of neurosecretory neurons of the hypothalamic supraoptic and paraventricular nuclei.
3 The neurosecretion collects, and dilates some axons and their terminals into Herring bodies. Gomori staining or EM shows the presence of granules in these axons, but not in the
4 pituicytes - a neuroglial kind of cell.
5 The secretion collects in terminals arranged as a palisade around blood vessels. Its release may involve electrical discharge in the axon and chemical factors in the 'synaptic' vesicles also present.
6 Two polypeptide hormones in the secretion are:

7 The neural lobe has a direct arterial supply from the inferior hypophyseal arteries to its fenestrated capillaries.

B PINEAL GLAND/EPIPHYSIS CEREBRI

l Originates as a dorsal outgrowth at the caudal end of the diencephalon. Unlike the pituitary, it is not connected directly by nerve fibres with the CNS.
2 The capsule of pia extends in septa to lobulate the organ, and carry in extensive blood vessels.
3 There is a regulatory autonomic nerve supply via the superior cervical ganglia.
4 Constituent cells 5 Increasing in number throughout life are mineral concretions - so-called brain sand (acervuli cerebri/corpora arenacea).
6 The pineal is responsive to changes in environmental light, initially mediated via the accessory optic tract and the suprachiasmatic nucleus.
Darkness raises the production of the enzyme hydroxyindole-O-methyl transferase (HIOMT), which methylates N-acetyl-serotonin to give melatonin.
7 Melatonin is part of the internal clock, matching the rhythm of alertness, and gonadal and other endocrine functions, to external light-based circadian and seasonal cycles. (In amphibia, melatonin also reduces the dispersal of pigment within melanocytes, hence the name.)

C THYROID GLAND

l General morphology
l Develops from an endodermal downgrowth at the base of the tongue. The thyroglossal duct, connecting it with its point of origin, later disappears. Two lateral lobes, an isthmus (and sometimes a pyramidal lobe) are established.
2 The inner, true, CT capsule sends in septa to partially enclose lobules.
3 In the lobules are rounded or elongated bodies - follicles, in a loose stroma of CT, with many blood vessels.

2 Thyroid follicle
l In man, they vary between 0.02 and 0.9 mm in diameter. A gland has several million follicles.
2 Filled with viscous fluid - thyroid colloid - variably acidophil or basophil, and often shrunken and showing knife chatters.
3 Lined by basophilic cuboidal follicular cells, varying in height as a simple epithelium on
4 a basal lamina, outside which is an extensive plexus of blood capillaries, and reticular fibres and fibroblasts.
5 Follicular cells are polarized with respect to the follicle lumen; the nucleus is central, the Golgi complex supranuclear; EM shows plenty of granular ER, some luminal microvilli, endocytotic vesicles, and lysosomes.
6 Between the follicular cells and the BL, and sometimes outside the BLs, lie occasional C cells (clear/parafollicular cells), having no direct access to the lumen, and no colloid droplets, but with small argyrophil, secretory granules.

3 Thyroid histophysiology
l C Cells

2 Follicular cells

D PARATHYROID GLANDS

l General morphology
l Derived embryologically from the 3rd and 4th pharyngeal grooves.
2 Adherent to the true capsule of the thyroid.
3 Each of the four or more rounded or ovoid bodies has a fine CT capsule and delicate, incomplete septa.
4 These septa carry vessels, nerves and many fat cells.

2 Histophysiology
l Supported on fine reticular fibres are many fenestrated blood capillaries and sheets and cords of
2 glandular cells:

3 Functions
(a) Secretory granules of chief cells are the polypeptide hormone, parathormone/PTH, released in response to low blood Ca2+, and acting on osteoclasts and macrophages to increase bone resorption.
(b) In the kidney, PTH: promotes the tubular reabsorption of calcium, and the 1, activation of vitamin D; and inhibits the renal tubular reabsorption of phosphate - a phosphaturic action.
(c) Unlike most other endocrine glands, no specific pituitary trophic hormone is involved in its control.

E ADRENAL/SUPRARENAL GLAND

l General morphology and development
l Elongated glands of cocked-hat or crescentic shape.
2 Composite of medullary and cortical tissues, linked by blood supply, but embryologically and functionally distinct.
3 Mesodermal cells of coelomic mesothelium differentiate into:
(i) inner, provisional or fetal cortex (involutes at birth); and
(ii) outer, permanent cortex.
4 Neural crest ectodermal cells migrate: (i) to coeliac ganglion; and (ii) then some go beyond to invade the adrenal cortical tissue and form the medulla.
5 Mature adrenal has a thick CT capsule, bringing arteries to serve radial capillaries draining down towards the venules and central vein of the medulla. Arterioles also penetrate the cortex to serve a medullary capillary bed.
6 The medulla is a long, thin strip of basophilic cells, which can be made outstanding by the chromaffin reaction - a darkening produced by dichromate ions.
7 The supporting element throughout is the reticular fibre.

2 Cortex
l Polyhedral glandular cells, in cords usually two cells wide, run roughly radially, along with sinusoidal capillaries.
2 Three layers are visible:

3 Lipid droplets (Sudanophilic and osmiophilic) contain cholesterol and cholesterol esters, used in conjunction with the Golgi body, smooth ER and special mitochondria, to produce two kinds of
4 steroid hormones: mineralo- and gluco-corticoids. Examples: 3 Medulla
l Two cell kinds: 2 Release is controlled by a direct, 'preganglionic', sympathetic innervation, terminating synaptically on the glandular cells.
3 The hormones released are: 4 The hormones are stored in characteristic membrane-bound granules, visible in EM. The granules form in relation to the Golgi body, but a dense GER is not required. They also contain enkephalins and chromogranin.
5 Both principal hormones are catecholamines, which can be converted by oxidizing agents, e.g., dichromate or ferric salts, to brown-coloured polymers - adrenochromes: this is the chromaffin reaction.

F KIDNEY

The kidney is not only the target for hormones, but it also makes several.
l Renin is an enzyme, formed in the juxtaglomerular modified muscle cells, that acts on a blood protein to form the potentially hypertensive angiotensin l. One triggering stimulus is the chloride concentration in the distal tubule detected by the macula densa cells.
2 l,25-hydroxycholecaliferol - the active form of vitamin D, needed for the intestinal absorption of Ca2+ and some direct actions on bone cells, is made in the kidney. Vitamin D from synthesis in the skin, or from the diet, is changed to 25-HCC in the liver, but the final 1,25 step is a renal task.
3 Erythropoietin is a protein growth factor, made by predominantly medullary renal fibroblasts, that stimulates the production of erythrocytes by marrow, e.g., when the atmospheric O2 falls at high altitude.

G APUD NEUROENDOCRINE AND PEPTIDE SYSTEMS

In the 1970s, the focus was on the amine metabolism that gave a unifying aspect to rather perplexing cells, scattered in many organs, which had been noticed and considered on an individual basis as clear (empty looking), or having granules reacting with silver salts. It turned out that most of these cell types made and released non-cytokine peptide mediators, to act locally or at a distance. The peptide story has now overwhelmed the amine or APUD idea, because these peptide factors are many, and are made and used for signalling in every part of the body, including the brain. The basis of the APUD classification is outlined below, because it helps explain aspects of pathology.

l APUD Within some endocrine glands, chemoreceptors, the brain, and dispersed in epithelia, are cells that form amine compounds. After an Amine Precursor has been taken Up, the cell Decarboxylates it to form serotonin (5-HT) from 5-hydroxytryptophane, or a catecholamine from dihydroxyphenylalanine (hence APUD).
Noticing that many of these cells secrete polypeptide hormones, Professor Pearse proposed a far-flung 'APUD' neuroendocrine system, secreting peptide mediators. The amines and peptides function variously as neurotransmitters, hormones, and modulators of neural action. Some vary their role by site. Some cells come from neural crest; for others, their origin is disputed.

2 Established APUD members
Peripheral
l Pancreatic islet cells -> insulin, glucagon, and somatostatin
2 Thyroid C cells -> calcitonin
3 Parathyroid chief cells -> parathormone
4 Gastrointestinal endocrine cells -> gastrin, secretin, pancreozymin/ cholecystokinin, glucagon, motilin, somatostatin, and many other active peptides. (Cells have a designating letter, if the hormone is known).
5 Other endocrine/neuroendocrine cells in respiratory and genito-urinary tract epithelia hold granules, reacting with silver salts in the argyrophilic and argentaffin ways of the GI-tract endocrine cells, and produce a variety of peptides, e.g., vasoactive intestinal polypeptide/VIP.

Tumours of these neuroendocrine cells often draw attention because of symptoms resulting from an excess of ectopic (out of place) polypeptide hormone, e.g., ACTH from the bronchial neuroendocrine cell, and/or an excess of serotonin, resulting in the flushing, bronchoconstriction, diarrhoea, etc. of the carcinoid syndrome.

Central
5 Pituitary
.. somatotrophs -> growth howmone (GH)
.. mammotrophs -> prolactin (PRL/MTH)
.. corticotrophs -> adrenocorticotrophic hormone (ACTH)
.. melanotrophs -> melanocyte-stimulating hormone (MSH)
6 Hypothalamic large neurosecretory cells -> oxytocin, vasopressin
7 Hypothalamic small neurosecretory cells -> releasing factors/hormones, e.g., LH.RF; and somatostatin (SRIF) inhibiting GH release from pituitary somatotrophs.
8 Pinealocytes -> melatonin

3 APUD members with an uncertain peptide role
The peptide substance normally formed, if any, has not yet been identified, or its role is unclear.
l Carotid-body type l cell and similar cells in the aortic and other chemoreceptive bodies contain norepinephrine and/or dopamine.
2 Chromaffin-system cells, in the adrenal medulla and abdominal paraganglia, contain catecholamines and enkephalins.
(The GI tract cells of 2.4 above, despite their old 'enterochromaffin' name do not form catecholamines.)
4 Melanocytes of skin, and dermal and ocular CT cells using amines to form melanin, come from the neural crest.

4 Neuroendocrine cells
The granular cells of the GI tract, airway, and genitourinary system produce a variety of peptide factors, some acting locally in a paracrine mode, others maybe having more distant effects. A common denominator is the presence along with the peptide(s) of certain materials in the dense-cored granules, e.g., chromogranin A or B, which provide markers for histopathologists seeking to find these relatively rare and dispersed cells.

H HEART, PANCREATIC ISLETS, TESTIS, OVARY and PLACENTA

Chapters 15.C.7, 25.A.5; 28.A.3; and 29.G.4 respectively.
William A Beresford, Anatomy Department, School of Medicine, West Virginia University, Morgantown, WV 26506-9128, USA - - e-mail: -- wberesfo@wvu.edu -- wberesfo@hotmail.com -- beresfo@wvnvm.wvnet.edu -- fax: 304-293-8159