Ghrelin localization in rat and human thyroid and parathyroid glands and tumours

Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is a 28 amino acid peptide originally isolated from rat stomach that has been primarily involved in the central neuroregulation of GH secretion and food intake. Previous studies demonstrated that ghrelin has a widespread expression in different normal cells and tissues, as well as in gastric, thyroid, testicular, breast and lung neoplasias. In the current study, we use molecular biology to detect ghrelin transcripts expression in rats, and immunohistochemical techniques to investigate the cellular distribution of this peptide in rat and human thyroid and parathyroid glands and tumours. Ghrelin was localized in thyroid C cells and in parathyroid cells. Thyroid carcinomas (medullar, follicular and papillary) and parathyroid adenomas also showed intense and diffuse immunostaining for ghrelin. These data provide direct morphological evidence that ghrelin may well be acting in a paracrine fashion in the regulation of thyroid follicular cell function. The diffuse ghrelin immunostaining found in the parathyroid gland opens up the possibility of its secretion to the bloodstream or its involvement in the regulation of the parathyroid function. Overall, expression of ghrelin in human and rat thyroid and parathyroid glands is highly suggestive of a conserved role of this molecule in the regulation of thyroid and parathyroid cell functio

Cellular distribution of growth hormone-releasing hormone receptor in human reproductive system and breast and prostate cancers

Growth hormone releasing hormone receptor (GHRH-R) mRNA and protein was first localized to the anterior pituitary gland, consequent with the action of its ligand on GH synthesis and release. Subsequent studies found GHRH-R also expressed in the hypothalamus and in systemic tissues including those of the reproductive system. In the present work, we studied the distribution of GHRH-R in human reproductive system of males and females by immunohistochemical method. GHRH-R immunostaining was localized in male reproductive system: Leydig cells, Sertoli and basal germ cells of the seminiferous tubules and prostate secretory cells. GHRH-R immunostaining was also demonstrated in the ovary: oocytes, follicular cells, granulosa, thecal and corpus luteum cells. Endometrial glands, placenta and normal mammary glands also showed GHRH-R immunostaining. Our results demonstrate the localization of GHRH-R in the reproductive system, which may mediate the direct action of GHRH in these tissues. Moreover, GHRH-R was demonstrated in prostate and breast carcinomas, opening a variety of possibilities for the use of GHRH antagonists in the treatment of prostatic and mammary tumors

Ghrelin localization in the medulla of rat and human adrenal gland and in pheochromocytomas

Objective: Ghrelin is predominantly produced by neuroendocrine cells of stomach and has been expressed in several normal and tumour endocrine tissues. It has been reported that the localization of ghrelin is exclusively in the cortex of human and rat adrenal gland and in adrenocortical tumours. This prompted us to analyze the expression of this peptide in medulla of human and rat adrenal glands and in human pheochromocytomas. Design and methods: Analysis of ghrelin mRNA expression in rat adrenal gland was conducted by means of semi-quantitative RT-PCR. Ghrelin localization was studied in medulla of human and rat adrenal gland by immunohistochemistry. In addition, we have carried out a double immunofluorescence with chromogranin A to determine the specific cell type expressing ghrelin immunoreactivity. Ghrelin expression was also analyzed in five cases of pheochromocytoma by immunohistochemistry. Finally, Western blotting analysis was performed with goat ghrelin antibody in the cortex and in the medulla of rat adrenal gland. Results: RT-PCR demonstrated expression of ghrelin mRNA in rat adrenal gland. We also detected ghrelin expression in virtually all rat pheochromocytes by immunohistochemistry and double immunofluorescence. Furthermore, we showed ghrelin immunoreactivity in the medulla of human adrenal gland and in pheochromocytomas. By Western blotting, we found the expression of ghrelin precursor, proghrelin and mature ghrelin in the medulla of rat adrenals. However, the cortex of rat adrenal gland only expressed ghrelin precursor. Conclusions: Our study is the first to demonstrate a medullar expression of ghrelin in human and rat adrenal gland; we also showed ghrelin expression in pheochromocytomas