Lecture by Prof.

Marina Kapitonova for the year 2 UiTM Dental Students

OBJECTIVES:
1. Define and provide endocrine glands. classification of the

2. Describe microscopic anatomy of the pituitary as the central endocrine gland. 3. To describe microscopic anatomy of the adrenal glands, thyroid and parathyroid glands as peripheral endocrine glands.

General provisions.

1. Endocrine system in collaboration with the nervous system, orchestrates homeostasis by influencing, coordinating, and integrating the physiological functions of the body. 2. Whereas the nervous system responds rapidly with a response of short duration, the endocrine system responds slowly, and the response is of longer duration. 3. Endocrine glands are responsible for the synthesis and secretion of chemical messengers known as hormones which are disseminated throughout the body by bloodstream where they act on specific target organs. Therefore endocrine glands possess an extensive vascular supply that is particularly rich in fenestrated capillaries. They have no excretory ducts as they discharge their product directly in blood. 4. Endocrine glands function by a regulatory system known as negative feedback in which production of a hormone affects a target organ to initiate a response that eventually reduces secretion of that hormone. 5. The endocrine system consists of several glands, composed of islands of secretory cells of epithelial origin, as well as of isolated groups of cells within certain organs, and individual cells scattered among parenchymal cells of the body.

Classification of the Endocrine System 1.Endocrine glands (pituitary, epiphysis, thyroid gland, parathyroid glands, adrenal glands). 2. Mixed glands (testes, ovaries, pancreas). 3. Paracrine system (APUD). Endocrine glands: 1. Central (pituitary hypothalamo-hypophyseal system; pineal gland epithalamo-epiphyseal system). 2. Peripheral (thyroid, parathyroid and adrenal glands, sex glands, pancreas). Peripheral endocrine glands: 1.Pituitary-dependent (thyroid gland, adrenal cortex, sex glands). 2.Pituitary independent (adrenal medulla, parathyroid glands, pancreas).

The hypophysis is a master endocrine gland connected to the hypothalamus at the base of the brain, with which is has important anatomic and functional relationship and formes hypothalamo-hypophyseal system providing the highest level of control of the endocrine functions. Similar relations exist between pineal gland and epithalamus forming epithalamoepiphyseal system. Other endocrine glands (thyroid, parathyroid, adrenal glands) are considered to be peripheral endocrine glands (purely endocrine ones). Pancreas, ovaries, testes combine functions of the endocrine and exocrine glands.

Pituitary Gland and its hormones

cavity of the 3rd ventricle optic chiasm pars tuberalis diaphragm sella mammil body median eminence

pituitary stalk
post. pituitary

dura mater

anterior pituitary

neural lobe

sphenoid bone sella turcica pituitary fossa

pars intermedia
fibrocollagenous setum with cysts

The pituitary or hypophysis is divided into adenohypophysis and neurohypophysis having different embryonic origin. Adenohypophysis includes pars distalis (or pars anterior), pars tuberalis and pars intermedia. Neurohypophysis is formed by the posterior lobe of the gland.

Scheme of pituitary

Pituitary gland, H&E

The pituitary is suspended from the hypothalamus (H) by the infundibulum which is composed of ther neural portion (infundibular stem, IS) and the surrounding pars tuberalis (PT). The 3rd ventricle of the brain is continuous with the infundibular recess (IR). Pars anterior (PA) is the largest portion of the pituitary which is glandular and secretes numerous hormones. Pars nervosa (PN) does not manufacture hormones but stores and releases them. Pars intermedia (PI) is located between pars anterior and pars nervosa, it frequently presents intraglandular cleft (colloid-filled cyst) which is a remnant of Rathkes pouch.

Anterior lobe of the hypophysis, toluidine blue staining Endocrine cells (E) of the adenohypophysis are arranged in groups and surrounded by capillaries (C). The capillaries are wide, endothelially lined vessels known as sinusoids.

E
C E

Pars distalis of the pituitary, H & E

Lobus anterior (or pars distalis) comprises 80% of the pituitary, while pars intermedia in humans is less developed. Pars distalis is composed of large cords of cells that branch and anastomose with each other. Traditionally cells of the anterior lobe of the pituitary have been classified into three types: acidophils (A), (cytoplasm staining by acidic dyes), basophils (B) (cytoplasm staining by basic dyes and PAS-method) and chromophobes (CO) which do not stain.

Pars Distalis of the Pituitary, H & E.

The chromophobes do not take up the stain well and only their nuclei are demonstrable. They make about 50% of cells of pars distalis. These cells are small, therefore chromophobes are easily recognizable since their nuclei appear to be clumped together. They represent either nonspecific stem cells or partially degranulated chromophils.

Adenohypophysis, PAS-Orage G.
On the picture acidophils (A) are stained bright, basophils (B) are stained dark while chromophobes (C) are not stained.

It is now customary to classify cells according to their hormone content which is demonstrable by modern immunohistochemocal methods of staing using antibodies to each hormone type. It was shown that acidophils are cells secreteing growth hormone and prolactine (i.e. somatotrophs and lactotrophs), and basophils (PAS+) are gonadotrophs, thyrotrophs or corticotrophs. Basophils stain well with hematoxylin and PAS which detect glycosil groups, as luteinizing hormone (LH), follicle stimulating hormone (FSG) and thyrocyte stimulating hormone (TSH) are glycoproteins, and the ACTH precursor protein is glycosylated.

Anterior lobe of the pituitary, immunohistochemical staining for somatotropin.

Most of the chromophil cells in the pituitary (40%) are acydophils, and among them the majority are somatotrophs (arrows). Besides the granules, there are mant parallel cysterns of the RER in the cytoplasm. In the malignant cells thick bundles of the intermediate filaments may be discovered. Most of the granules measure 350-450 nm in diameter, though the range is between 300 and 600 nm.

Anterior pituitary, immunohistochemical staining for prolactin.

Lactotrophs make up to 25% of the anterior pituitary. While some are rounded and polygonal (arrows), most are compressed by adjacent cells into narrow angular profiles). They increase in size and number during pregnancy and lactation. Ultrastructurally they have a prominent Golgi compared to all other anterior pituitary cells and their granules measure 200-350 nm in diameter. Interesingly, exocytosis may be seen at their lateral borders (misplaced exocytosis) as well as in the usual site adjacent to capillary basement membrane. This feature can be used in diagnostic assessments as it is limited to lactotrophderived tumors.

Anterior pituitary, immunohistochemical staining for ACTH.

Accounting for 15-20% of the anterior pituitary, corticotrophs (arrow) are large and polygonal in shape, as shown in this micrograph stained to show ACTH by immunoperoxidase technique. Many corticotrophs possess an unstained perinuclear vacuole called the enigmatic body, which is derived from secondary lysosomes. Granules in corticotrophs are large band typically measure 250-700 nm in diameter. Large perinuclear bundles of intermediate cytokeratin filaments are prominent ultrastructurally and these become even more prominen in glucocorticoid excess, when they are visible under the light microscope as pink-staining inclusions (Crookes hyalin).

Anterior pituitary, immunohistochemical staining for FSH.

Constituting around 10% of anterior pituitary cells, gonadotrophs (arrow) are scattered as single cells or small groups throughout the gland as seen in this section stained for the beta-subunit of FSG by immunoperoxidease technique. Both FSH and LH may be evident within the same cell. Ultrastructurally the granules are 150-400 njm in diameter. Following ablation of the ovaries or testes, gonadotrophs develop extensive cytoplasmic vacuolation. This is due to dilation of the endoplasmatic reticulum by stored product and caused by the loss of feedback inhibition by gonadal steroids. Such cells, large rounded and vacuolated on light microscopy, are called castration cells.

Anterior lobe of the pituitary, E, 12,000

It is also possible to distinguish cells of the anterior pituitary by elecron microscopy. The electron microphotograph reveals the presence of the dence core granules in the cytoplasms of adonocytes. Chromophobes fail to stain because they contain very few granules, and may be lactotrophs, somatotrophs, gonadotrophs, thyrotrophs or corticotrophs by nature.

Posterior pituitary, H & E.

Posterior pituitary is composed of axons which originate from cells in the hypothalamus and possess numerous neurosecretory granules containing either oxytocin or vasopressin together with a carrier protein termed neurophysin, and ATP. Where axons are adjacent to capillaries they form fusiform swellings filled with neurosecretory granules (Hering bodies). The posterior pituitary also contains specialized stellate-shaped glial cells called pituicytes. In the micrograph the axons are seen a pale fibrillary background in which the nuclei of pituicytes (P) and small capillary vessels are present.

Hypothalamic neurons secrete releasing/inhibiting factors in response to chemoreceptive and neural inputs. These hormones diffuse into capillaries at the median eminence and are carried to the anterior pituitary in the portal vessels. Astrocyte foot processes surrounding the cappilaries form part of their diffusion barrier.

capillary

neural synapse hypothalamic neuron releasing/ Inhibiting factor

astrocyte
astrocyte foot process

capillary at median eminence portal vessel basement membrane endothelial cell

anterior pituitary cells Hypothalamic control of anterior pituitary hormone production.

Summary of Histology of Pituitary and Hypophysis

Loca- Gene- Speral cell cific tion

type cell type

Hormone

Target tissue/ organ especially muscle and bone

Nature Gra- Stain- Funcof hor- nule ing tions mone size protein 300- Orange stimulates growth, 400 G promotes nm

pars acido- somadista- phils tolis of trophs the pituitary

somatotrophin or growth hormone (GH)

protein synthesis in bones and muscles, influences carbohydrate and lipid metabolism.

acido phil

mammotroph

prolactine

breast

protein

550- Orange initiates & regulates 700 G lactation, nm promotes

mammary development

Loca Gene- SpeHor-tion ral cell cific cell mone

type type

Target tissue/ organ

Nature Gra- Stain- Funcof hor- nule ing tions mone size 150- PAS 200 nm
stimulates development of follicles in the ovary & seminiferous tubules in the testes stimulates corpus luteum development & progesteron secretion: necessary for ovulation and estrogen secretion

pars basop gonadista hil do-lis trophs of follithe culopitui trophs -tary basop luteohil trophs

follicle ovary & glycotestis prostimutein lating hormone

luteiovary Glyco- 150- PAS nizing (corpus pro200 hormo luteum) tein nm ne

Loca- Gene- Speral cell cific tion

type cell type

Hormone intersticial cell stimulating hormone, probably same as LH adrenocorticotropin (ACTH)

TarNature Gra- Stain- Funcget of hor- nule ing tions organ mone size testis glycoprotein 150- PAS & 200 aldenm hydestimulates Leidig fuchsin cells to PAS produce testosterone
stimulates synthesis of adrenocortical steroid hormones controls thyroxine production & release

pars baso- gonadista- phil dolis of troph the pituitary

baso- cortiphil cotroph

adre- Polynal pepcortex tide

200- PAS 250 nm

baso- thyro- thyroidthyphil troph stimularoid ting hormone-TSH

glycop 130rotein 150 nm

Location

Gene- Speral cific

Hormone

Tar-get Natu- Gra- Stain- Funcorgan re of nule ing tions horsize mone 200- PAS 300 nm stimulates melanocyte expansion
storage and release of neurohormones of hypothalamus: vasopressin, oxytocin
smooth polymuscle, pepespeci- tide ally uterus

pars basointer- phil media

melanotroph APUD

melano- skin of polycyte sti- lower pepmulating animals tide hormone (MSH)

pars neuro pituinervo- -glia cyte sa of the pituitary

hypothala mus
neurosecretory neurons

none

neurons oxyin para- tocin ventricular nuclei

100- Gomori stimulates contraction 300 of the utenm

rine wall during parturition.

Loca- Gene- Spetion ral cific hypo- neuro- neuthala secre- rons in mus tory supraneuopticalrons nuclei

Hor- Target mone organ vaso pressin (antidiuretic hormone - ADH renal collecting tubules, arterioles

Nature Gra- Stain- Funcof hor- nule ing tions mone size polypeptide 100- Gomori increases water 300 absorption nm

of renal collecting tubules, constricts arterioles to incease pressure causes release of the anterior pituitary hormones; inhibits release of the anterior pituitary hormones

neurosecretory neurons

neurons in tuberal nuclei

six re- pars leasing distalis factors (RF);

peptide

pars two known distalis inhibiting factors

peptide

corpus callosum

3rd ventricle

pineal gland

tentorium cerebelli light

eye
nervus opticus

n.suprachiasmaticus
central sympathetic pathways

pituitary gland optic chiasm

superior cervical ganglion cerebellum

Diagram shows the location of the pineal gland. Output of pineal melatonin is modulated by light through nervous pathways which input as sympathetic innervation to the gland. It is also thought to influence gonadal activity (suppression). The parenchyma is composed of pinealocytes and interstitial cells. Pinealocytes are resposible for secretion of serotonin and melatonin, while the interstisial cells are believed to astroglia-like cells.

Pineal Gland

Thyroid possesses three features of special significance:

1) it is unique among the endocrine glands in that it manufactures hormones, stores them extracellularly and releases for use as required,

2) it is the only endocrine gland that depends on the external environment for raw materials of its hormones, 3) it possesses one of the richest blood flow compared to adrenal and other glands,

4) thyroid hormones are the only among amino-acid-derived hormones which being lipid-soluble, diffuse through the cell membrane and binds to intracellular hormone receptor proteins in the target cells (other amino acid-derived hormones receptors are present in the cell membrane of the target cells).

I. General Morphology
1. The thyroid gland consists of right and left lobes connected across the middle line by a narrow portion, the isthmus (and sometime pyramidal lobe). 2. Its weight is somewhat variable, but is usually about 30 grams. 3. It is slightly heavier in the female, in whom it becomes enlarged during menstruation and pregnancy.

4. Parenchyma of thyroid gland: follicles + interfollicular clusters of calcitoninocytes.

Human Thyroid Gland, H. & E., 162 x.

follicles colloid blood vessels

100 m
Stroma: the inner, true, connective tissue (CT) capsule sends in septa to partially enclose lobules separated by a loose CT, with many blood vessels. Follicles are the structural units of the thyroid gland. Note variations in shape (rounded or tubular) and size (0.05 to 0.5 mm in diameter). Close packing with a thin reticular network between adjacent follicles.

Human Thyroid Gland, H. & E.

follicle

colloid

Lined by basophilic cuboidal follicular cells, varying in height from squamous to low columnar as a simple epithelium on a basal lamina, outside which is an extensive plexus of blood capillaries, and reticular fibres and fibroblasts. Follicular cells are polarized with respect to the follicle lumen. Nucleus is placed centrally or basally. Colloid is found in the lumen of follicles. It is variably acidophil or basophil, and often shrunken and showing knife chatters.

Thyroid follicles:
1. In man they vary markedly between 0.02 and 0.9 mm in diameter.
2. Larger follicles filled with colloid have a squamous or cuboidal epithelium. 3. Glands with follicles that have predominantly squamous epithelial cells are considered to be hypoactive. 4. When the gland is stimulated to synthesize thyroid hormone, the follicular epithelial cells become columnar and the amount of colloid is reduced. 5. Each follicle can store several weeks supply of hormone within colloid. 6. A gland has several million follicles. 7. Chemical composition of colloid is a glycoprotein-iodine complex (thyroglobulin). The follicles release about 100 mg of hormone daily. Of the several iodinated compounds found in the gland the 3, 5, 3-triiodothyronine is hormonally the most active.

Human Thyroid Gland A. H. & E.; B. periodic acid-Schiff and hematoxylin.

Follicle cell nuclei Follicles Thyroglobulin Thyroglobulin B 20 m

In A, the colloid in the lumen of the follicle is not stained. In B, the colloid is specifically stained red with the periodic acidSchiff method because of the chemical composition of colloid, which is a glyco-protein-iodine complex (thyroglobulin).

Thyroid Physiology:

Follicular cells: (a) Are stimulated by pituitary thyrotrophic hormone (TSH) to produce and release two iodinated amino-acid hormones tetraiodothyronine (thyroxine/T4) and 3,5,3-triiodoL-thyronine(T3), (b) which are stored in the colloid, as component amino acids of the glycoprotein - thyroglobulin. (c) The hormones accelerate general specific metabolic processes of the body. and

(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. iii. iv. v. vi. Iodide oxidation - throughout the cell. (ii) Synthesis of thyroglobulin - basal cell, granular ER, Golgi body, by vesicle to the lumen. In the luminal thyroglobulin, tyrosine residues are iodinated, then pairs condense. Cellular retrieval of thyroglobulin from colloid storage cell's apical region by endocytosis. Transport to lysosomes, where cathepsins degrade the large modified molecule.

vii. Release of freed iodothyronines - out of the base of the cells into the blood.
viii. Binding to intracellular proteins after entering cytoplasm and slow use over a period of several days to weeks (both T3 and T4 bind to nuclear thyroid hormone receptor proteins, but T3 binds with a much greater affinity than does T4, which accounts for the greater biological activity of T3).

Diagram of the synthesis and iodination of thyroglobulin (A) and release of thyroid hormone (B).

Biological Effects of Triiodothyronine and Thyroxine.

1) Normal thyroid function is essential for the normal growth, development, and tissue metabolism of the body.

2) T3 and T4: stimulate transcription of many genes that encode various types of proteins, resulting in a generalized increase in cellular metabolism that may be as great as twice resting rate; a) stimulate carbohydrate metabolism,

b)

decrease synthesis of cholesterol, phospholipids, and triglycerides but increase synthesis of fatty acids and the uptake of various vitamins,
T3 and T4 also increase the growth rate in the young, facilitate mental processes, and stimulate endocrine gland activity.

c)

CLINICAL CORRELATES:
Increased thyroid hormone production: a) decreases body weight, b) increases heart rate, c) increases metabolism, muscle function, and appetite. respiration,

d) hormone production increases from 5 to 15 times normal.

Excessive amounts of thyroid hormone (hyperthyroidism) cause:

a) muscle tremor and weakness, b) tiredness, c) impotence in men, d) frequent menstrual bleeding in women. e) excessive appetite and thirst, f) weight loss, g) rapid respiration, sweating, heat intolerance (due to an increase d basal metabolic rate),

h) increase in heart rate (tachycardia)

i) emotional disturbance and nervousness k) bulging (protrusion) of the eyes (exophthalmos) - occurs due to an increase in orbital support tissue. l) increases of the size of the thyroid gland two to three times above normal

Thyroid Gland, Hyperplasia, Diffuse

colloid in lumen of follicle

papillary infoldings

In thyroxic hyperplasia a number of follicular cells increases, papillary folds of acinar epithelium develop. In addition each epithelial cell is large columnar and the edges of colloid are scalloped, indicating active removal of stored colloid for processing into thyroxine.

CLINICAL CORRELATIONS: Overactivity of the thyroid (hyperthyroidism) may be due to a number of factors. In Graves disease, the thyroid is overactive even with low levels of THS, due to an immunologic disturbance in which an immunoglobulin has an effect similar to that of TSH (autoimmune IgG antibodies bind to TSH receptors which stimulate thyroid follicular cells).

Deficiency of thyroid hormone:

a)

from the time of birth results in:

1a) a dwarf child who is mentally retarded (cretinism). 2a) slow heart rate, muscular weakness, and gastrointestinal disturbances. Thyroid hormone given to infants at an early stage of cretinism can alleviate the symptoms.

b) in adults:

1b) mental slowing, 2b) cold intolerance, 3b) reflex changes, 4b) skin changes 5b) fatigue, sleeping for up to 16 hours per day, 6b) muscular sluggishness, 7b) slowed heart rate, decreased cardiac output and blood volume 8b) failure of body functions, 9b) constipation, 10b) loss of hair growth.
Patients with severe hypothyroidism may develop myxedema, which is characterized by bagginess under the eyes and swollen face that is due to nonpitting edema of the skin, infiltration of excess glycosaminoglycans, and proteoglycans into the extracellular matix.

PARAFOLLICULAR CELLS OF THE THYROID GLAND

In thyroid between the follicular cells and the basal lamina (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.

Histophysiology of C-cells:
(a) they are APUD cells of neural crest origin, (b) and produce the polypeptide calcitonin for the reduction of high plasma Ca2+ and phosphate levels by inhibiting bone resorption by osteoclasts and decreasing calcium and phosphate reabsorbtion by renal tubules. It may increase the rate of osteoid mineralization. (c) although diffuse, in sum they form a gland antagonistic to the action of the parathyroids. (d) the secretion of calcitonin results from elevation of blood calcium concentration above normal levels.

PARAFOLLICULAR CELLS (C CELLS) Thyroid gland, H. & E.

C

Parafollicular cells are located between follicular cells or in the interstitial connective tissue.

General Morphology and Microstructure of C-cells.

1. Although C-cells are 2 to 3 times larger than follicular cells, they account for only about 0.1% of the epithelium. 2. Parafollicular cells may be found intimately associated with thyroid follicles or as isolated or interstitial clusters of cells (the latter location, which is less common for human thyroid, explains the archaic name parafollicular cells). They are not readily found in routine thicker sections of the thyroid gland. The photomicrographs above are from 1.5 m plastic sections. 3. Although parafollicular cells appear, at the light microscopic level, to be in intimate contact with thyroid colloid, they are, in fact, separated from colloid by thin intervening processes of adjacent thyroid follicular cells. 4. Ultrastructurally they contain dense-core neurosecretory granules that are characteristic of neuroendocrine cells.

PARAFOLLICULAR CELLS (C CELLS)

Thyroid gland
Parathyroid gland Thyroid follicular cells Colloid parafollicular cells

A
Thyroid follicles

Follicle filled with colloid Parafollicular cells Mast cells

B
Parafollicular cells

H. & E., A. 119 x; B. & C. 169 x.

Interstitial aggregation of parafollicular cells

C
A 100 m

B & C 50 m

Parathyroid gland, Human, H. & E.

Adherent to the true capsule of the thyroid, the small parathyroid glands (4 to 5 mm in diameter) and are usually found on the posterior surface of the thyroid gland.

C A

C
Stroma: Each of the four (may range from 2 to 12) rounded or ovoid bodies has a fine connective tissue capsule and delicate, incomplete septa which divide the gland in lobules. . These septa carry vessels, nerves and many fat cells. Parenchyma: supported on fine reticular fibres are many fenestrated blood capillaries and sheets and cords or plates of chief cells (small, 7-10 m diameter; some dark, some light: contain glycogen, lipofuscin pigment, and argyrophil secretory granules; form occasional small follicles.) and oxyphil cells (larger, acidophilic, and often occur in clumps; no secretory granules). The most abundant type is the chief (or principal) cell, which is functionally important.

Parathyroid, Human, H. & E.

C

Chief cells: with prominent nucleus, round and centrally located, and cytoplasm that stains variably and may be light or dark depending upon its secretory activity. The second type, oxyphilic (acidophilic or eosinophilic) cells, occurs in fewer numbers in small clumps or nests among chief cells. Larger than chief cells. Oxyphilic cells usually arise after puberty and increase in number beyond the age of 40 but their specific function is unknown. May be derived from chief cells. Oxyphil cells: occurs in small clumps and in fewer numbers. These cells usually have small densely staining heterochromatin and an oxyphilic cytoplasm whose perimeter is usually well defined.

3.Functions
(a) Secretory granules of chief cells are the polypeptide hormone, parathormone/PTH, which is important in calcium and phosphate metabolism acting mainly on bone and the kidney: 1a) it is released in response to low blood Ca2+, 2a) acts on osteoclasts and macrophages to increase bone resorption, 3a) it also removes calcium phosphate directly from bone matrix, and, via intermediary factors, from osteoblasts;. (b) in the kidney: 1b) PTH: promotes the tubular reabsorption of calcium 2b) inhibits the renal tubular reabsorption of phosphate - a phosphaturic action; (c) promotes conversion of 25-hydroxyvitamin D to 1,25 dihydroxyvitamin D (this metabolite increases calcium absorbtion by the gut);

(d) unlike most other endocrine glands, no specific pituitary trophic hormone is involved in its control.

Clinical Correlates:
Parathyroid glands are essential for life whereas calcitonin of the thyroid appears to provide a complementary mechanism for fine adjustment of blood calcium level and is not essential for life. In the absence of parathyroid hormone, there is a pronounced decrease in blood calcium resulting in tetany, abnormal twitching, the intense, involuntary spasm of skeletal muscle. caused by changes in excitability at the neuromuscular junction, and death. Dietary addition of calcium and especially administration of parathyroid hormone relieves the abnormal spasms, preventing death of the organism. Abnormal levels of calcium may result in abnormal deposition of calcium in the kidneys and muscle. Abnormally increased blood levels of calcium occur at the expense of bone, which may fracture as a result.

Adrenal Gland
Cortex: Zona glomerulosa (narrow subcapsular zone of cortex) secretes mineralocorticoids, mainly aldosterone. Zona fasciculata (broad, yellow mid-zone of cortex) secretes glucocorticoids, mainly cortisol and corticosterone. Zona reticularis (narrow inner zone of cortex) secretes mainly androgenic steroids.

medulla

cortex

z.reticularis

z.fasciculata

Adrenal medulla (central, enclosed by cortex, brown) is neuroendocrine and secretes epinephrine and norepinephrine (noradrenaline).

z.glomerulosa

capsule

Adrenal Cortex, H & E.

The zona glomerulosa is composed of small compact cells (C) arranged in clumps and separated by stroma composed largely of thin-walled capillaries. The cells contain scanty lipid droplets associated with well developed SER and comparatively little RER.

Adrenal Cortex, H & E.

Zona fasciculata contains cells arranged in vertical columns, which are usually 2-3 cells wide, the columns being separated by capillaries (Cap).

Adrenal Cortex, Zona Reticularis. H & E.

The inner zona reticularis produces androgenic steroids and some glucocorticoids, but normally only in small amounts. The inner zone of adrenal cortex is thinner than the zona fasciculata, but thicker than the zona glomerulosa. It is composed of cells with eosinophylic cytoplasm arranged in an anastomosing network of clumps and columns with a capillary network closely apposed to the cell membranes. A characteristic feature of this layer when stained with H & E is the present of brown pigment (lipofuscin). To the naked eye the layer appears pale brown, whereas the zona fasciculata is bright yellow.

Adrenal Medulla, H&E

Because of their high catecholamine content, adrenal medullary cells develop an intensive brown color when exposed to air or to a strong oxidizing agent, such as potassium dichromate, due to the formation of brown pigment when the amines are oxydized. This is the basis of their antiquated name chromaffin cells. Adrenal medullary cells (E- and N-cells) show their large nuclei and finely granular cytoplasm.

Adrenal Medulla, TEM, x20,000

Large dense-core granules corresponding to norepinephrine (N) and epinephrine (E) granules.