Figure 206

This specimen of the pars distalis is stained with brilliant crystal scarlet, aniline blue, and Martius yellow to distinguish the various cell types and connective tissue stroma. The cords of cells are surrounded by a delicate connective tissue stroma stained blue. The sinusoidal capillaries are seen in close association with the parenchyma and contain erythrocytes stained yellow. In the region shown here, the acidophils (Ac) are the most numerous cell type present. Their cytoplasm stains cherry red. The basophils (Bas) stain blue. The chromophobes (Ch), though few in number in this particular region, are virtually unstained. x640.

• Somatotropes (GH cells) are most commonly found within the pars distalis and constitute approximately 50% of the parenchymal cells in the anterior lobe of the pituitary gland. These medium-sized, oval cells exhibit round, centrally located nuclei and produce GH (somatotropin). The presence of eosinophilic vesicles in their cytoplasm classifies them into the acidophil cell type. Two hypothalamic hormones regulate the release of GH from somatotropes: growth hormone-releasing hormone (GHRH) and somatostatin, which inhibits GH release from the somatotropes. Hormonally active tumors that originate from somatotropes are associated with hypersecretion of GH and cause gigantism in children and acromegaly in adults.

• Lactotropes (PRL cells, mammotropes) constitute 15 to 20% of the parenchymal cells in the anterior lobe of the pituitary gland. These are large, polygonal cells with oval nuclei. They produce PRL. In their storage phase, lactotropes exhibit numerous acidophilic vesicles (the histologic feature of an acidophil). When the content of these vesicles is released, the cytoplasm of the lactotrope does not stain (the histologic feature of a chromophobe). Secretion of PRL is under inhibitory control by dopamine, the catecholamine produced by the hypothalamus. However, thyrotropin-releasing hormone (TRH) and vasoactive inhibitory peptide (VIP) are known to stimulate synthesis and secretion of PRL. During pregnancy and lactation these cells undergo hypertrophy and hyperplasia, causing the pituitary gland to increase in size. These processes account for the larger size of the pituitary gland in the multiparous female.

table 20.3. Electron Microscopic Characteristics of Cells Found in the Anterior Lobe of the Pituitary Gland

Cell Type

Somatotrope Lactotrope

Corticotrope

Gonadotrope Thyrotrope

Size/Shape

Medium/oval

Large/polygonal

Medium/polygonal

Small/oval

Large/polygonal

Nucleus/Location

Round/central, with prominent nucleoli

Oval/central

Round/eccentric

Round/eccentric Round/eccentric

Secretory Vesicle Size/ Characteristics

Other Cytoplasmic Characteristics

Dense: 350 nm, closely packed

Inactive: 200 nm, sparse Active: dense, pleomorphic, 600 nm, sparse

100-300 nm

Dense: 200-250 nm

Dense: <150 nm

None

Lysosomes increase after lactation

Lipid droplets, large lysosomes, perinuclear bundles of intermediate filaments

Prominent Golgi apparatus, distended rER cysternae

Prominent Golgi apparatus with numerous vesicles

• Corticotropes (ACTHcells) also constitute 15 to 20% of the parenchymal cells in the anterior lobe of the pituitary gland. These polygonal, medium-sized cells with round and eccentric nuclei produce a precursor molecule of ACTH, known as proopiomelanocortin (POMC). These cells stain as basophils and also exhibit a strong positive reaction with PAS reagent, because of the carbohydrate moieties associated with POMC. POMC is further cleaved by proteolytic enzymes within the corticotrope into several fragments, namely ACTH, lipotrophic hormone (fi-LPH), melanocyte-stimulating hormone (MSH), ¡3-endorphin, and enkephalin. ACTH release is regulated by corticotropin-releasing hormone (CRH) produced by the hypothalamus.

• Gonadotropes (FSH and LH cells) constitute about 10% of the parenchymal cells in the anterior lobe of the pituitary gland. These small, oval cells with round and eccentric nuclei produce both LH and FSH. They are scattered throughout the pars distalis and stain intensely with both basic stains (thus classifying them as the basophil cell type) and PAS reagent. Many gonadotropes are capable of producing both FSH and LH. However, immunocyto-chemical studies indicate that some gonadotropes may produce only one hormone or the other. The release of FSH and LFI is regulated by gonadotropin-releasing hormone (GnRH) produced by the hypothalamus. Both FSH and LH play an important role in male and female reproduction, which is discussed in Chapters 21 and 22.

• Thyrotropes (TSH cells) constitute about 5% of the parenchymal cells in the anterior lobe of the pituitary gland. These large, polygonal cells with round and eccentric nuclei produce TSH (thyrotropic hormone, thyrotropin). They exhibit cytoplasmic basophilia (basophils) and stain positively with PAS reagent. Release of TSH is also under the hypothalamic control of TRH, which also stimulates secretion of PRL. TSFI acts on the follicular cells of the thyroid gland and stimulates production of thyroglobulin and thyroid hormones.

Pars Intermedia

The pars intermedia surrounds a series of small cystic cavities that represent the residual lumen of Rathke's pouch. The parenchymal cells of the pars intermedia surround colloid-filled follicles. The cells lining these follicles appear to be derived from various secretory cells. Transmission electron microscopy reveals that these cells form apical junctional complexes and have vesicles larger than those found in the pars distalis. The nature of this follicular colloid is yet to be determined; however, often, cell debris is found within it. The pars intermedia contains basophils and chromophobes (Fig. 20.7). Frequently, the basophils and cysts extend into the pars nervosa.

The function of the pars intermedia cells in humans remains unclear. From studies of other species, however, it is known that basophils have scattered vesicles in their cytoplasm that contain either a- or /3-endorphin (a morphine-related compound). In frogs, the basophils produce MSH, which stimulates pigment production in melanocytes and pigment dispersion in melanophores. In humans, MSH is not a distinct, functional hormone but is a byproduct of /3-LPH posttranslational processing. Because MSH is found in the human pars intermedia in small amounts, the basophils of the pars intermedia are assumed to be corticotropes.

Pars Tuheralis

The pars tuheralis is an extension of the anterior lobe along the pituitary stalk. It is a highly vascular region containing veins of the hypothalamohypophyseal system. The parenchymal cells are arranged in small clusters or cords in association with the blood vessels. Nests of squamous cells and small follicles lined with cuboidal cells are scattered in this region. These cells often show immunoreactivity for ACTH, FSH, and LH.

6 50 chapter 20 I Endocrine Organs BOX 20.1

Functional Considerations: Pituitary Secretion and Hypothalamic Regulating Hormones

The release of hormones from the anterior lobe of the pituitary gland is under significant control by the hypothalamus, which regulates release of hypothalamic regulating hormones into the hypophyseal portal veins. These hypothalamic regulating hormones can stimulate or inhibit secretion of pituitary hormones. The hypothalamic regulating hormones are produced in the cells of the hypothalamus in response to circulating levels of hormones. Thus, the cells of the anterior lobe of the pituitary gland can be selectively inhibited or stimulated. A simple negative feedback system controls the synthesis and discharge of the releasing hormones. Consider the production of thyroid hormone (see Fig. 20.5). If blood levels of thyroid hormone are high, TRH is not produced or released. If blood levels of thyroid hormone are low, the hypothalamus discharges TRH into the hypothalamohypophyseal portal system. Release of TRH stimulates specific cells within the anterior lobe of the pituitary gland to produce TSH, which, in turn, stimulates the thyroid to produce and release more thyroid hormone. As the thyroid hormone level rises, the negative feedback system stops the hypothalamus from discharging TRH. Most of the tropic hormones produced by the anterior lobe of the pituitary gland are regulated by releasing hormones. PRL production is primarily regulated by the inhibitory effect of dopamine; i.e., PRL secretion is tonically inhibited by the release of dopamine by the hypothalamus.

POSTERIOR LOBE OF THE PITUITARY GLAND (NEUROHYPOPHYSIS)

The posterior lobe of the pituitary gland is an extension of the central nervous system (CNS) that stores and releases secretory products from the hypothalamus

The posterior lobe of the pituitary gland, also known as the neurohypophysis, consists of the pars nervosa and the infundibulum that connects it to the hypothalamus. The pars nervosa, the neural lobe of the pituitary, contains nonmyelinated axons and their nerve endings of approximately 100,000 neurosecretory neurons whose cell bodies lie in the supraoptic and paraventricular nuclei of the hypothalamus. The axons form the hypothalamohypophyseal tract and are unique in two respects. First, they do not terminate on other neurons or target cells but end in close proximity to the fenestrated capillary network of the pars nervosa. Second, they contain secretory vesicles in all parts of the cells, i.e., the cell body, axon, and axon terminal. These vesicles may be specifically stained with the aldehyde-fuchsin, aldehyde-thionine, and chrome-hematoxylin methods; by specific procedures for the disulfide groups of cystine; and more specifically by immunochemical reactions. Because of their intense secretory activity, the neurons have well-

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