Neuroendocrinology of the pituitary gland

The hypophysial-portal chemotransmitter hypothesis of control of the anterior pituitary was first set forth in the 1940s on the basis of physiological studies of the effects of lesions of the hypothalamus, and of section of the pituitary stalk on pituitary function. Morphological demonstration of specific neuropeptide pathways in the hypothalamus, which project to the median eminence, and the chemical identification of releasing hormones in the hypothalamus have fully established this theory. Specific neuropeptides have been isolated which stimulate the secretion of ACTH (CRF, corticotrophin releasing hormone), TSH (TRH, thyrotropin releasing hormone), GH (GHRH, growth hormone releasing hormone), and the gonadotropins (LHRH, luteinizing hormone releasing hormone; GnRH, gonadotropin releasing hormone). Prolactin secretion is regulated by both an inhibitory hormone (dopamine), and by one or more releasing factors. A factor inhibitory to GH and TSH secretion has also been identified. All factors except for the prolactin inhibitory hormone (which is a biogenic amine) are peptides, all synthesized as part of large prohormones. These substances have all been introduced into medical and veterinary practice where they are useful for regulation of pituitary abnormalities, and study of normal physiology.     

Prolactin-derived amyloid in the aging pituitary gland.

Small amyloid deposits occur commonly in different organs in association with aging. As in other amyloids, the fibrils in the age-associated forms are built up by specific proteins, unique to every histological type. The amyloid proteins that have been identified in localized amyloid of human endocrine organs have all been of polypeptide hormone nature, and these include calcitonin, islet amyloid polypeptide (amylin), and atrial natriuretic factor. In the present study, we add prolactin to the increasing group of known amyloid proteins and show that this hormone constitutes the amyloid fibrils of pituitary glands of aging individuals.     

Embryonic development of the pituitary gland in the chick

Pituitary glands of chicken, from stages 20 (70 approximately 72 h of incubation) to 46 (20 days) of Hamburger and Hamilton (1951), were studied by immunocytochemical and histological stainings and India ink injection into blood vessels. Using the distribution pattern of 6 types of immunoreactive adenohypophyseal cells and the location of pituitary stalk as guideposts, we found how specific areas in the epithelium of Rathke's pouch differentiate into specific regions of the adenohypophysis at 20 days. In the sagittal plane, the walls of Rathke's pouch were tentatively divided into the upper part (A(1) + A(2)) and lower part (A(3)) of the anterior wall, and the posterior wall (P(1) + P(2) + P(3)). The cephalic lobe was mainly assembled by the proliferation of parenchymal cells in the areas A(2) + A(3) + P(2) of Rathke's pouch epithelia at 3 days of incubation. The caudal lobe was derived from A(1) + P(1) + P(3). The pars tuberalis was derived from A(1) + A(2). Thus, the avian adenohypophysis is established at 13 days, though the blood supply to the pars distalis is established at 20 days. Therefore, the cephalic lobe and caudal lobe of the pars distalis and the pars tuberalis of the chicken adenohypophysis are derived from specific areas of the cell cords of Rathke's pouch at 3 days of incubation.     

Incidental adenomas of the human pituitary gland

Using conventional histological technique, we investigated 44 adenomas (31 men, 13 women) incidentally found in 36 pituitaries (25 men, 11 women) obtained from 1,117 unselected autopsies. The overall incidence of adenomas was 3.2% (men, 3.8%; women, 2.4%) without any significant sex predominance. Size, age distribution, and histological appearances of these adenomas were similar to those previously reported by others. Statistical analysis showed that the adenomas had a predilection for occurrence at the anterior margin of the gland. We further investigated 33 available adenomas with immunohistochemistry using antibodies for various adenohypophyseal hormones, S-100 protein, and glial fibrillary acidic protein, of which 6 contained growth hormone, 3 contained growth hormone and prolactin, 7 contained prolactin, 6 contained follicle-stimulating hormone, 3 contained follicle-stimulating and luteinizing hormones, 2 contained thyroid-stimulating and adrenocorticotrophic hormones (separately), and 6 contained no adenohypophyseal hormones. None of adenomas revealed neoplastic proliferation of folliculostellate cells. To investigate tumor proliferation, nucleolar organizer regions were studied in 9 adenomas using the argyrophil method. The mean number per nucleus was slightly higher than that of corresponding, nontumorous adenohypophysis at a statistically significant level. No adenoma caused symptoms of adenohypophyseal hormone abnormalities.     

Nitric oxide synthase in the human pituitary gland.

Nitric oxide (NO) is generated by the NO synthase family of isozymes, which is present in many mammalian cells. The constitutive NO synthase isozymes generate NO, which acts via signal transduction mechanisms in the regulation of many functions including vascular tone and blood pressure, and the inducible isozymes mediate immunological mechanisms by cytotoxic and cytostatic effects. To determine whether NO has a role in anterior pituitary cell function, immunohistochemistry and in situ hybridization analyses were used to study NO synthase expression in normal and neoplastic human pituitary tissues. Brain NO synthase was localized in the anterior pituitary in secretory and in folliculo-stellate cells and in the posterior pituitary. Pituitary adenomas had higher levels of brain NO synthase protein and mRNA compared with normal pituitaries. Endothelial NO synthase was also present in anterior and posterior pituitary cells and in endothelial cells of the pituitary. Immunoblotting studies with brain NO synthase antibodies detected a slowly migrating approximately 155-kd band and more rapidly migrating approximately 90-kd and approximately 60-kd bands. Endothelial NO synthase, but not macrophage NO synthase, was also detected in the pituitary by immunoblotting studies, confirming the immunohistochemical observations. These findings indicate that NO synthase is expressed in normal and neoplastic human pituitary tissues with increased levels of brain NO synthase protein and mRNA in adenomas compared with non-neoplastic pituitary cells and suggest that NO may play a regulatory role in hormone secretion in anterior pituitary cells.     

Coated vesicles in the rat anterior pituitary gland.

Ultrastructural documentation of the formation of coated vesicles in prolactin cells of the rat anterior pituitary gland is presented. Coated vesicles were observed forming from the secretory granular membrane in the Golgi area and between the Golgi complex and the plasmalemma. They were also found budding off the membrane lining the exocytotic pocket. Following peroxidase reaction product could be seen forming from the membrane of the exocytotic pocket and adjacent to it. These vesicles were found in transit towards the Golgi area or within lysosomes. It is proposed that these coated vesicles are important for membrane conservation and that this is occurring in developing secretory granules near the Golgi complex, in more mature secretory granules and at the level of the plasmalemma during exocytosis.