Windsor . CO 80550

CHAPTER 19. The Endocrine System

The microscopic study of animal tissues and cells

Plate 19-1. The Thyroid Gland 
Plate 19-2. The Adrenal Cortex 
Plate 19-3. Cells Of The Adrenal Gland 
Plate 19-4. The Pituitary Gland 
Plate 19-5. Cells Of The Pituitary Gland

This atlas began with a discussion of Entropy, the notion that everything tends toward disorder; here, we will consider the effects of Entropy at a different level of organization. In Chapter 1, Cells, we discussed the enormous entropic possibilities inherent in a “typical” human cell possessed of some 10 billion individual protein molecules. This chapter deals with the even greater entropic possibilities inherent in a whole human being made up of some 50 trillion individual cells, each of which contains 10 billion protein molecules.

The human organism, composed of 50 trillion cells, copes with the tremendous inherent possibilities for disorder by superb mechanisms for intercellular communication in the nervous system and the endocrine system.

Given that humans are large, watery cellular aggregates, intercellular communication is arranged in two ways. For cells to communicate, they must make contact with one another, either directly, by physical cell-to-cell contact, as in the nervous system, or indirectly, through the common solution in which they all bathe, as in the endocrine system. The nervous system can readily be envisioned as a communication network with myriad branching processes and synaptic contacts all carrying information from place to place in the body. The endocrine system, however, is harder to envision as a communication system because the fluid-borne molecules that carry information in solution from cell to cell are too small to be seen. In the endocrine system, an endocrine organ – basically a “ductless gland” – secretes a chemical messenger, or hormone, directly into the bloodstream. The hormone, rapidly carried through the circulatory system to all parts of the body, has specific effects on cells that have specific receptor molecules on their cell membranes that bind the hormone. The hormone, then, exerts its effect at some distance from the organ that secreted it. Consequently, the endocrine system has all the virtues of a communication system. Its bits of information, whose effects are far-flung, are blood-borne.

These two communications systems are tied together both anatomically and physiologically; the endocrine system and nervous system have profound effects on one another. Much of their interaction occurs in a part of the brain called the Hypothalamus, in which neurons monitor specific body functions. When a deficit or imbalance of some sort is detected, the Hypothalamus secretes releasing factors into blood vessels, which carry them immediately to the pituitary gland. The pituitary will in turn secrete a Trophic Hormone that will stimulate one of the many glands of the endocrine system to secrete a hormone that will affect the appropriate target cells. Thus, the endocrine system corrects the imbalance originally detected by the nervous system. An example of this sort of cells of the anterior pituitary sit in front of the hypothalamic regulation of endocrine function is described in detail in the text of Plate 19-4.

The interrelationship between the nervous system and the endocrine system is manifest in the very structure of several endocrine organs themselves, where nerve cells and endocrine cells exist side by side in the same organ. In the adrenal gland, for example, the endocrine cells of the cortex are wrapped around a Medulla made of nervous tissue. In the adrenal gland, cells of the endocrine system and the Autonomic Nervous System live within the same endocrine gland. In the pituitary, the endocrine posterior pituitary, which is made of nervous tissue. In the pituitary, then, cells of the central nervous system and the endocrine system meet and live as near neighbors.

The endocrine system is highly complex, and its organs are many and varied. Some endocrine organs, such as the Ovary and Testis, have already been discussed. In this chapter, several of the major endocrine organs are illustrated by light and electron microscopy – the thyroid gland, the adrenal gland, and the pituitary gland.

The first endocrine organ to be described in this chapter is the thyroid gland – a small, butterfly-shaped organ, weighing less than 45 g, that is essential for the control of the body’s metabolic rate. Without the thyroid gland, one would become sluggish, weak, and slow of thought. Fortunately, loss of the thyroid can largely be compensated by administration of its major endocrine product, Thyroid Hormone.

Located in the neck in front of the larynx, the thyroid gland consists of a series of functional units called follicles that range from small to large (nearly 1 mm in diameter). The follicles are filled with a dense, viscous Colloid that contains Thyroglobulin, a large, complex protein to which molecules of Thyroid Hormoneare attached. When the epithelial cells of the follicles of the thyroid gland elaborate Thyroid Hormone, they link the hormone to Thyroglobulin molecules. The Thyroglobulin is then stored in the Colloid in the lumen of the follicles. When the hormone is needed by the body, the epithelial cells begin a series of complicated biochemical maneuvers. First, Thyroglobulin is taken up from the lumen of the Follicle by Pinocytosis; the cells drink the Colloid they have made and stored. Next, the Thyroglobulin taken into the cells is broken down by lysosomes, and the Thyroid Hormone is set free. Finally, the Thyroid Hormone is released from the base of the epithelial cells into nearby blood or lymph capillaries, from whence it is distributed to the tissues of the body.

Just as the thyroid gland has a unique function in the endocrine system, so does it have a unique structure. The thyroid gland is quite easy to identify in sectioned material. In Figure A, a light micrograph, the organization of thyroid tissue into follicles is apparent. The follicles vary in size and being nearly spherical, present a series of circular profiles.

Each Follicle consists of a simple Cuboidal Epithelium (E) that surrounds a lumen filled with Colloid (C). The follicles are separated from one another by delicate strands of loose connective tissue that emanate from the capsule that surrounds the gland. The majority of the epithelial cells, called principal cells, are concerned with the elaboration and secretion of Thyroid Hormone. Their structural appearance can change dramatically with their state of function; whereas inactive thyroid glands may have a squamous follicular epithelium, active follicles may have a cuboidal or low Columnar Epithelium. The principal cells can proliferate (*) by undergoing cell division.

Several follicles of the same thyroid gland are illustrated by electron microscopy in Figure B. The Follicle in the center of the field (F1) has been sectioned across its center and displays the typical circular profile of a simple Cuboidal Epitheliumthat surrounds a Colloid-filled lumen (C). The Follicle at the upper left (F2), however, has been cut tangentially; only a small portion of the lumen and Colloidare visible. The Follicle in the upper right (F3) has been cut tangentially as well; in this case, the knife passed through the epithelium alone and missed the Colloidcompletely, presenting the somewhat misleading appearance of a Follicle without a lumen that looks like a solid ball of cells. Although most of the epithelium consists of principal cells, an occasional parafollicular cell (P) is evident. Parafollicular Cells are neurosecretory cells that release the hormone Calcitonin, which inhibits bone resorption by osteoclasts and has the effect of lowering blood calcium levels. Parafollicular Cells, also called clear cells and C cells, do not reach the lumen of the Follicle; instead, they are associated with the many blood and lymph capillaries that are present in the highly vascular thyroid gland.

Plate 19-1
Plate 19-1, Figure A. A light micrograph of the thyroid glancd. C, colloid in luman of follicle; Ca, capillary; E, follicular epithelium; P, parafollicular cell; *, dividing cell. 1,600 X

Figure B. Electron micrograph of the same thyroid gland in Figure A. C, collid; Ca, blood capillary; E, Epithelium; F1, F2, and F3, follicles cut in diferent planes of section; L, lymph capillary; P, parafollicular cell. 2,800 X


Figure A is a light micrograph of a cross section through half of the monkey adrenal gland. All the major histologic subdivisions of the gland are evident at low magnification. Working from the outside in (from the top to the bottom of the micrograph), the gland is covered by a connective tissue capsule (C) that serves to contain the soft underlying endocrine tissues. Beneath the capsule lies the outermost “layer” of the adrenal cortex, called the Zona Glomerulosa (ZG). The zona glomerulosa is concerned with the elaboration and secretion of a class of Steroid hormones that, taken together, are called Mineralocorticoids – hormones concerned with salt balance in the blood. Chief among the hormones secreted by the Zona Glomerulosa is AldosteroneAldosterone promotes resorption of sodium from the Glomerular Filtrate by the proximal tubules of the kidney. Beneath the Zona Glomerulosa lies the zona fasciculata (ZF), a lightly stained region of the adrenal cortex that secretes glucocorticoids, a class of Steroid hormones concerned with Glycogen metabolism. The major glucocorticoids secreted by the Zona Fasciculata of the Adrenal Cortex include Cortisol and Cortisone. Beneath the Zona Fasciculata lies the Zona Reticularis, which produces adrenal androgens. The entire adrenal cortex surrounds the Adrenal Medulla (M). The Medulla is quite different in structure from the cortex. It consists of a cluster of sympathetic nerve cells, modified to secrete catecholamines, that produce Norepinephrine and Epinephrine.

As is the case in all endocrine organs, the adrenal gland releases its hormones into the bloodstream, which distributes them to the various target organs throughout the body. Consequently, the adrenal gland, like all endocrine organs, is highly vascular. The capillaries (Ca) in the adrenal gland are not only extremely numerous, they are also quite large. In addition to being vessels of large caliber, the capillaries in the adrenal are fenestrated capillaries: their walls are perforated by holes that readily permit the passage of large molecules.

Plate 19-2
Plate 19-2, Figure A. Light micrograph of a cross section through the adrenal gland of the squirrel monkey. C, capsule; Ca, Fenestrated Capillary; M, Adrenal Medulla; ZF, Zona Fasciculata; ZG, Zona Glomerulosa; ZR, Zona Reticularis. 170 X Figure B. Electron micrograph through the outer region of the Adrenal Cortex of the squirrel monkey. C, capsule; Ca, Fenestrated Capillary; ZF, zona fasciculate; ZG, zona glomerulosa. 850 X Figure C. Electron micrograph through the inner region of the Adrenal Cortex of the squirrel monkey. Ca, Fenestrated Capillary; ZR, Zona Reticularis. 1,000 X

Figure B shows part of the capsule (C), the zona glomerulosa (ZG), and the Zona Fasciculata (ZF) by electron microscopy. Here, the ovoid, or glomerular, arrangement of cells in the Zona Glomerulosa is evident. Similarly, the arrangement of cells in the zona fasciculata into parallel cords, or fascicles, is obvious. Both of these regions stand in sharp contrast to the zona reticularis, shown in

Figure C. Here, the cells are grouped into thin, interconnecting strands, conferring an open, reticular appearance to the region. In all regions of the cortex, the microanatomy of the cells betrays their functional organization as Steroid-secreting cells. They have a high content of lipid droplets – membrane-limited vesicles filled with fatty Steroid hormones – and they have unique Mitochondria with tubular Cristae. These and other features of the adrenal gland will be described in more detail on the following plate.


In addition to these features, the endocrine cell of the Zona Glomerulosa possesses large numbers of Mitochondria (M) with tubular Cristae. Many Steroid-producing cells, such as the cells of the adrenal cortex and the Interstitial Cells of the Testis, contain Mitochondria with Cristae arranged in a tubular configuration. The functional significance of this highly ordered arrangement of Cristae is presently unknown.

Figure B is an electron micrograph of a cell from the Zona Fasciculata of the Adrenal Cortex. In having Mitochondria (M) with tubular Cristae and a large population of lipid droplets (L), it shares features with the cells of the overlying Zona Glomerulosa. Fine differences exist, however. The lipid droplets, large and dense in the cells shown in Figure A, are small, less dense, and more numerous in the cells in Figure B, perhaps reflecting differences in the quantity and quality of hormone produced by each cell type. The cells of the Zona Fasciculata produce glucocorticoids such as Cortisone, whereas those of the Zona Glomerulosaproduce Mineralocorticoids such as Aldosterone.

Figure C depicts a portion of the Adrenal Medulla as viewed by electron microscopy. The Adrenal Medulla, markedly different in structure from the cortex, actually represents a Ganglion of the Sympathetic Nervous System whose neurons have largely become specialized as neurosecretory cells. The vast majority of cells within the Medulla, called Chromaffin Cells (C), are specialized to produce the catecholamines Epinephrine and Norepinephrine. These cells are filled with tiny, electron-dense, Catecholamine-containing granules. Like the Adrenal Cortex, the Adrenal Medulla is highly vascular, containing many large fenestrated capillaries (Ca). Occasional Ganglion cells (G), large nerve cells not filled with neurosecretory granules, are present. The Medulla is held together by fine strands of connective tissue (CT) rich in reticular fibers. Capillaries are often found in association with these wispy strands of connective tissue.

The adrenal gland, then, is really two endocrine glands in one, in that it has an epithelial component (the cortex) and a neural component (the Medulla). The pituitary gland, too, as we shall see in the next plate, has an epithelial component (the anterior pituitary) and a neural component (the posterior pituitary).

Plate 19-3

Plate 19-3, Figure A. Electron micrograph of cells of the Zona Glomerulosa of the Adrenal Cortex of the squirrel monkey. Ca, Fenestrated Capillary; E, Erythrocyte; L, lipid droplet; Ly, Lymphocyte; M, mitochondrion; N, Nucleus; *, Microvilli; arrow, fenestration in capillary. 5,300 X

Figure B. Electron micrograph of the Zona Fasciculata from the same Adrenal Cortex photographed in Figure A. L, lipid droplet; M, mitochondrion; N, Nucleus. 5,600 X Figure C. Electron micrograph of the Medulla of the same adrenal gland photographed in Figures A and B. C, chromaffin cell; Ca, Fenestrated Capillary; CT, connective tissue strands; G, Ganglion cell. 2,300 X 2


An example of the pituitary gland as an interface is the feedback loop involving Thyrotropin-releasing factor (TRF), Thyrotropin, and Thyroid Hormone. Because Thyroid Hormone serves to control the body’s metabolic rate, levels of Thyroid Hormone circulating in the blood are critical and must be carefully controlled. When blood levels of Thyroid Hormone fall, nerve cells in the central nervous system-specific neurosecretory cells in the Hypothalamus of the brain-become stimulated to secrete TRF. TRF is released into the bloodstream and travels directly to the pituitary gland through a special system of blood vessels called the hypothalamic-hypophyseal portal system. TRF stimulates special cells in the pituitary called thyrotropes to secrete the hormone Thyrotropin. When released into the bloodstream, Thyrotropin travels to the thyroid gland and promotes the secretion of Thyroid Hormone, which raises the titer of that hormone in the blood to appropriate physiologic levels.

In addition to serving as an interface between the nervous and endocrine systems, the pituitary gland has a dual histologic nature: it has an epithelial component, the Adenohypophysis, and a neural component, the Neurohypophysis. Areas of both components are shown in the figure at right, a low-magnification light micrograph of a sagittal section through the monkey pituitary gland. Here, the nervous component of the gland, the Pars Nervosa (PN), is connected directly with the Hypothalamus of the brain by axons that, taken together, form the Infundibulum(I) – a slender stalk of nerve tissue that suspends the pituitary gland from the base of the brain. Anterior to the Pars Nervosa is the pars distalis (PD), the largest subdivision of the pituitary gland, commonly referred to as the anterior lobe of the pituitary. In man and primates, the Pars Intermedia (PI) is a thin strip of tissue that lies between the Pars Distalis and the Pars Nervosa. Above the Pars Distalis, a collar of cells of unknown function called the Pars Tuberalis (PT) surrounds the Infundibulum (I).

The microanatomic appearance of the Pars Nervosa is radically different from that of the Pars Distalis. The pars nervosa consists of axons and their terminals. The cell-bodies of those axons are all in the brain’s Hypothalamus. These hypothalamic neurons are specialized for neurosecretion, and their neurosecretory products are two hormones – Oxytocin, which stimulates milk let-down and uterine Smooth Muscle contraction in females, and Vasopressin, which promotes water retention by the kidneys. These hormones collect in swollen Axon terminals within the Pars Nervosa. The pars distalis, on the other hand, consists of glandular epithelial cells specialized for the elaboration and secretion of many hormones, including ThyrotropinGrowth Hormone (GH), ProlactinLuteinizing Hormone (LH), Follicle-stimulating hormone (FSH), and Adrenocorticotropic Hormone (ACTH). Specific cell types, identified by immunohistochemistry and often distinguishable by electron microscopy, are responsible for the secretion of specific hormones.

Plate 19-4
Plate 19-4, Low-magnification light micrograph of a sagittal section through the pituitary gland of the squirrel monkey. BV blood vessels of the Hypothalamic-Hypophyseal Portal System; I, Infundibulum; PD, Pars Distalis (anterior lobe); PI, Pars Intermedia (intermediate lobe); PN, Pars Nervosa; PT, Pars Tuberalis. 120 X

As the previous plate clearly illustrates, the Adenohypophysis and Neurohypophysis look quite different from one another when viewed with the light microscope. The vast structural differences between the two major regions of the pituitary gland are even more striking when examined by electron microscopy.

Figure A is a low-magnification electron micrograph of the Pars Distalis of the Adenohypophysis. The pars distalis secretes six major hormones, including Thyrotropin, GH, Prolactin, LH, FSH, and ACTH. It is now widely accepted that each hormone is secreted by a single type of cell identifiable by immunohistochemical markers. Standard histologic sections, stained with hematoxylin-eosin, reveal three classes of morphologically distinct cells: acidophils, basophils, and Chromophobes, all named for their staining characteristics. Thin sections, viewed under the electron microscope, reveal several cell types distinguishable by the types of electron-dense Secretory Granules they contain.

The acidophils of the Adenohypophysis contain large (300-nm) granules that stain with eosin; acidophils include cells that secrete Growth Hormone or Prolactin. Basophils, which have small (150-nm) granules that stain with hematoxylin, include cells that secrete either Thyrotropin, FSH, LH, or ACTH. Chromophobesare believed to represent acidophils or basophils that have become degranulated after secretion of hormone. In Figure A, several cells (S) contain large, electron-dense granules. Although it is impossible to make a positive identification of these cells, they are in all likelihood Somatotropes – cells that secrete GH. Of the two cell types that contain large granules, Somatotropes are the more numerous. Other endocrine cells (B) have markedly smaller electron-dense granules. These cells correspond to the basophils seen under the light microscope; it is impossible to tell what kind of hormone they elaborate without resorting to Antibody-labeling techniques. All of the cells have the ultrastructural characteristics of protein-secreting cells; that is, they have an extensive rough Endoplasmic Reticulum(RER), a well-developed Golgi Apparatus, and numerous electron-dense granules that are actually membrane-limited secretory vesicles filled with the proteinaceous hormone produced by the cell. Many large, fenestrated capillaries (Ca), large enough to be called sinusoids, course between the endocrine cells of the Adenohypophysis. The fenestrations in the capillaries facilitate rapid passage of large molecules to and from the endocrine cells.

Figure B is a low-magnification electron micrograph of the Neurohypophysis of the same pituitary gland. There is almost no ultrastructural similarity between the Adenohypophysis and the Neurohypophysis. There are, for example, very few cell bodies in the Pars Nervosa, because the cell bodies of the Neurohypophysis lie in the Hypothalamus of the brain. The Neurohypophysis, then, is actually a direct extension of the brain itself. Most of its substance consists of axons (A) and swollen Axon terminals (AT) (also called Herring bodies) of neurosecretory cells that produce the octapeptide hormones Oxytocin and Vasopressin. Consequently, the Neurohypophysis functions largely as an organ of storage that releases Oxytocin and Vasopressin into the bloodstream when they are required by the body. Nuclei of several cell bodies, however, are present. These nuclei (N) belong to specialized cells called PituicytesPituicytes are not endocrine cells; instead, they are similar to glial cells and seem to play a role in the maintenance of the axons of the Neurohypophysis.

Pituitary Gland

Plate 19-4
Plate 19-4, Figure A. Electron micrograph of the Pars Distalis of the Adenohypophysis. B, basophils with small granules; Ca, fenestrated capillaries; RER, rough encloplasmic reticulum; N, Nucleus of somatotrope; S, somatotrope; arrow, large granules in Cytoplasm of somatrotrope. 2,600 X

Figure B. Electron micrograph of the Pars Nervosa of the Neurohypophysisfrom the same pituitary gland shown in Figure A. A, Axon; AT, Axon terminals filled with neurosecretory vesicles; N, Nucleus of pituicyte; P, pituicyte. 5,200 X