Microvessel density and VEGF expression in pituitaries of pregnant women.

OBJECTIVE: In pregnant women, the pituitary is enlarged and the prolactin (PRL) secreting cells increase in size and number. This PRL cell hyperplasia is associated with hyperprolactinemia. The aim of the present work was to investigate adenohypophysial vascularization and immunoexpression of vascular endothelial growth factor (VEGF) in pituitaries of pregnant and post-partum women and compare the results with age-matched adenohypophyses of nonpregnant women who had no endocrine diseases. DESIGN: Pituitaries (n=18) obtained by autopsy from female patients of reproductive age who had died during pregnancy, after abortion or during post-partum were immunostained for CD-34 and VEGF using the streptavidinbiotin- peroxidase complex method. RESULTS: The results showed that microvessel densities and VEGF immunoexpression in the adenohypophyses of pregnant and post-partum women were similar to those found in the control pituitaries. CONCLUSION: It can be concluded that pituitary enlargement and PRL cell hyperplasia in pregnant women may occur without neovascularization and increased VEGF immunoexpression.

Ghrelin immunoexpression in the human hypophysis.

The aim of this study was to immunohistochemically localize ghrelin in autopsy-obtained, nontumoral human pituitaries. Double immunostaining was also undertaken to determine the pituitary cell type expressing both adenohypophysial hormones and ghrelin. Results showed that ghrelin is present in the adenohypophysis, its immunoexpression being cytoplasmic, weak-to-moderate, and localized to a subset of cells. Double immunostaining showed that ghrelin is present in 51% to 90% of growth hormone-producing, luteinizing-producing, and α-subunit-producing cells. Ghrelin immunoexpression was less frequently observed in other adenohypophysial cell types, being seen in 30% of adrenocorticotropin and follicle-stimulating hormones, 15% of thyrotropin, and 10% of prolactin-immunoreactive cells. Ghrelin immunopositivity was also seen in nerve fibers and Herring bodies of the neurohypophysis and pituitary stalk. More work is needed to elucidate the role of ghrelin in adenohypophysial and neurohypophysial endocrine activity. It may well be that ghrelin exerts an autocrine/paracrine effect and can modulate hormone synthesis and release.

Pituitary immunoexpression of ghrelin in anorexia nervosa.

Ghrelin, an orexigenic hormone, is known to occur in the normal anterior pituitary where its physiologic role is uncertain but may include promotion of appetite. We sought to investigate anticipated differences in adenohypophysial and neurohypophysial ghrelin immunoexpression between normal subjects and patients with anorexia nervosa who had succumbed to complications of the disease. We hypothesized that the glands of anorexia nervosa patients would show relative diminished action in ghrelin content. The study included 12 autopsy-derived pituitaries of anorexia nervosa and 10 control glands. The streptavidin-biotin-peroxidase complex method and double immunohistochemical staining method were used to determine which cell types expressed both ghrelin and adenohypophysial hormones. Nontumorous control pituitaries were also obtained at autopsy. In anorexia nervosa and control adenohypophyses, ghrelin was mainly localized in somatotrophs and to a lesser extent in corticotrophs and gonadotrophs. Ghrelin accumulated within nerve fibers and Herring bodies in the neurohypophysis and pituitary stalk. In the controls, ghrelin expression was apparent in only a few cases. It was mild and only along few nerve fibers. In the adenohypophyses of anorexia nervosa patients, ghrelin was not depleted. It appears that in these patients, ghrelin is transported in excess from the hypothalamic neurohypophysial tract to the neurohypophysis.

Ghrelin immunoexpression in pituitary adenomas.

Ghrelin, an orexigenic hormone, is normally produced mainly in stomach. In addition, it has been demonstrated in gastric carcinoid tumors and less often in other neuroendocrine tumors. We investigated ghrelin expression by immunohistochemistry (streptavidin-biotin-peroxidase complex method) in the full spectrum of resected pituitary adenoma subtypes. Quantification of staining considered both the frequency of ghrelin-reactive tumor cells as well as their staining intensity. Cytoplasmic ghrelin immunopositivity was identified in several adenoma subtypes. Cellular staining varied considerably. In addition, the intensity of cell staining differed within the same tumor and between adenoma subtypes. The highest scores were noted in GH producing adenomas exposed to long-acting somatostatin analogs. In decreasing order, lower scores were encountered in ACTH adenomas in Cushing disease, silent subtype 3 adenomas, untreated GH adenomas, silent corticotroph adenomas of subtypes 1 and 2, dopamine agonist-treated PRL adenomas, ACTH adenomas in Nelson syndrome, and gonadotroph adenomas. No significant immunoreactivity was noted in TSH, untreated PRL, and null cell adenomas. The high immunoexpression of ghrelin in GH adenomas exposed to long-acting somatostatin analogs remains unexplained, but may be due to either increased ghrelin production or to suppression of its release. Based on our findings, it appears that ghrelin immunopositivity does not serve as a biomarker of biologic behavior, prognosis and therapeutic responsiveness in pituitary adenomas.