William A Beresford MA, D Phil ©
Professor of Anatomy
Anatomy Department, West Virginia University, Morgantown, USA
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
3 Divisions of the pituitary gland
| 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
(* together form hypophyseal stalk)
4 Embryological origins
- (a) Adenohypophysis develops from the ectodermal Rathke's pouch
above the oral cavity.
- (b) Rostral wall of Rathke's pouch becomes the anterior lobe; caudal
wall gives the intermediate lobe; the cleft between the intermediate and
anterior lobes occludes to a line of cysts; and the dorsolateral corners of
the pouch give the pars tuberalis.
- (c) Neurohypophysis comes as a downgrowth of the floor of the
diencephalon. The brain connection is maintained.
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
3 Pars distalis
- (a) Thick, branching cords and plates of cells, supported on
basal laminae and reticular fibres. Between the cords run wide sinusoidal
capillaries of fenestrated endothelial cells on their own BLs.
- (b) Classical division of the cells was into acidophils (40 per
cent), basophils (l0 per cent), and chromophobes (50 per cent).
- (c) Chromophobes are sparsely granular, small, pale, and often
clustered together. They are thought to be less active forms of the five
secretory, granular, chromophil cell kinds.
- (d) Chromophils can be distinguished by various stains, since some
form peptide hormones, others glycoproteins; by EM, from the size,
density and shape of the granules; and by immunostaining, for LM
- (i) ACIDOPHILS
Somatotroph - makes growth hormone (GH)/somatotrophin
(STH); stained by orange-G
Lactotroph/Mammotroph - makes prolactin/mammotrophin
(MTH); stained by erythrosin
- (ii) BASOPHILS, staining also with PAS and aniline blue
Thyrotroph gives thyrotrophic hormone (TSH/TH)
Gonadotroph gives luteinizing hormone (LH) and follicle-stimulating
hormone (FSH)/interstitial cell-stimulating hormone (ICSH)
Corticotroph makes adrenocorticotrophin (ACTH)
by cleaving pro-opiomelanocortin (POMC) appropriately
- (e) Hypothalamic regulation of the adenohypophysis is via the
hypothalamo-hypophyseal portal circulation, and for gonadotrophins,
ACTH, and TSH, functions by negative feedback thus:
This simplification ignores the inhibitory factors, such as
hypothalamic somatostatin preventing the release of growth hormone.
- Hypothalamic neurons are specialized to be sensitive to a blood
deficiency of the target gland's hormone, e.g. thyroxine.
- From the sensitive neuron's terminal, a neurosecretory, chemical peptide
releasing factor, e.g. TH-RH/TH-RF, passes into
- blood capillaries of the median eminence, whence it drains down
- via the portal circulation to the pars distalis.
- The releasing factor passes out of the blood to activate the appropriate
- chromophil cell, which produces more trophic hormone, e.g.,
- The trophic hormone passing in the blood to the target gland,
- promotes an increased output of target gland hormone, thyroxine,
whose raised blood level
- then reduces the activity of 1. the sensitive hypothalamic neurons, i.e.,
the system uses a negative feedback.
- (f) The hypothalamus thus acts as an endocrine organ.
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
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.
- (a) oxytocin/pitocin: makes mammary gland myoepithelial cells and
uterine smooth muscle contract;
- (b) vasopressin/pitressin/antidiuretic hormone (ADH): makes the
kidney collecting tubule permeable to water, and influences vascular
and gut smooth muscle.
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
4 Constituent cells
5 Increasing in number throughout life are mineral concretions - so-called
brain sand (acervuli cerebri/corpora arenacea).
- (a) Pinealocytes: basophilic, with secretory inclusions and lipid
droplets; nuclei indented; many ribosomes and smooth ER; innervated by
sympathetic fibres; and release melatonin.
- (b) Interstitial glial cells: 5 per cent; stellate with long processes.
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
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
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,
3 Thyroid histophysiology
l C Cells
2 Follicular cells
- (a) Are APUD cells of neural crest origin,
- (b) and produce the polypeptide calcitonin for the reduction of
high plasma Ca2+ and phosphate levels.
- (c) Although diffuse, in sum they form a gland antagonistic to the
action of the parathyroids.
- (a) Are stimulated by pituitary thyrotrophic hormone (TSH) to
produce and release two iodinated amino-acid hormones - tetraiodo-thyronine
(thyroxine/T4) and 3,5,3-triodo-L-thyronine(T3),
- (b) which are stored in the colloid, as component amino acids of the
glycoprotein - thyroglobulin.
- (c) The hormones accelerate general and specific metabolic processes of
- (d) Electron radioautography has shown the sites in the sequence of
hormone production by the follicular cells:
- (i) Iodide concentration - basal part of the follicular cell.
- (ii) Iodide oxidation - throughout the cell.
- (iii) Synthesis of thyroglobulin - basal cell, granular ER, Golgi body, by
vesicle to the lumen.
- (iv) In the luminal thyroglobulin, tyrosine residues are iodinated, then
- (v) Cellular retrieval of thyroglobulin from colloid storage - cell's
apical region by endocytosis.
- (vi) Transport to lysosomes, where cathepsins degrade the large modified
- (vii) Release of freed iodothyronines - out of the base of the cells into
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.
l Supported on fine reticular fibres are many fenestrated blood capillaries
and sheets and cords of
2 glandular cells:
- (a) Chief cells: small, 7-l0 µm diameter; some dark, some
light: contain glycogen, a Golgi complex, lipofuscin pigment, and
argyrophil secretory granules; form occasional small follicles.
- (b) Oxyphil cells; larger, acidophilic, and often occur in clumps;
cytoplasm is packed with mitochondria; no secretory granules; serve
no known role. More oxyphil cells are seen in older individuals.
(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
(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
7 The supporting element throughout is the reticular fibre.
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
- (a) Zona glomerulosa - under the capsule, rounded balls or groups
of columnar cells with dark nuclei.
- (b) Zona fasciculata - long, straight cords of large cells, swollen
with lipid droplets.
- (c) Zona reticularis - network made up of cells, small and often
lipid-free; lies nearest to the medulla.
4 steroid hormones: mineralo- and gluco-corticoids.
- (a) Aldosterone (mineralo-corticoid) helps control water and electrolyte
balance, e.g., by promoting renal Na+ reabsorption, and having
repercussions on blood pressure; secreted in the Z. glomerulosa, and
released in response to angiotensin II.
- (b) Cortisol (gluco-corticoid) helps control carbohydrate metabolism,
e.g., facilitates protein catabolism and gluconeogenesis (thus
interfering with processes requiring a high rate of protein synthesis,
such as wound repair and antibody responses): formed in Z.
fasciculata and reticularis in response to pituitary ACTH, itself
released under hypothalamic control; glucocorticoids affect the cells and
ground substances of connective tissues.
- (c) Other glucocorticoids, and significant amounts of sex hormones, in
Z. Fasciculata and reticularis.
l Two cell kinds:
2 Release is controlled by a direct, 'preganglionic', sympathetic
innervation, terminating synaptically on the glandular cells.
- (a) Sparse ganglion nerve cells, probably serving vascular smooth
muscle in arterioles and the central vein.
- (b) Chromaffin cells: large, granular, and arranged around venules,
with their other pole by blood capillaries; by far the major cell type.
- (c) Schwann cells to accompany the nerve fibers.
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.
- (a) Norepinephrine (transmitter substance for sympathetic,
- (b) Epinephrine (increases cell respiration, cardiac output, and
glucose mobilization, for the great muscular effort needed in fighting
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.
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
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
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
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
.. 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
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
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.