Ghrelin as an anti-inflammatory and protective agent in ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) continue to be the most frequent cause of damaged tissues. Injured tissues resulted from the first ischemic insult, which is determined by the interruption in the blood supply, followed by subsequent impairment induced by reperfusion. In addition, ischemia-reperfusion injury is mediated by tumor necrosis factor (TNF) and other cytokines that activate complements and proteases responsible for free radical production. However, earlier studies have reported the protective roles of bioactive peptides during ischemia reperfusion injury. In fact, ghrelin is a peptide hormone discovered since 1999 as GH secretagogue and its production was identified in gastric X/A-like endocrine cells in rats and P/D1 type cells in humans. To date, this peptide receives growing attention due to its pleiotropic action in the organism and its role in maintaining energy homeostasis. Ghrelin is also involved in stress responses, assuming a modulatory action on immune pathways. Previous studies have identified many other functions related to an anti-inflammatory role in ischemia reperfusion injury. Under these challenging conditions, studies described acylated and unacylated ghrelin in activation and/or inhibition processes related to ischemia-reperfusion injury. The aim of this article is to provide a minireview about ghrelin mechanisms involved in the proinflammatory response of I/R injury. However, the regulatory processes of ghrelin in this pathologic event are still very limited and warrant further investigation.

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.

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.

Regulation of peroxisome proliferator activated receptor-gamma in rat pituitary.

Peroxisome proliferator activated-receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily and, in addition to its relation with obesity and insulin sensitivity, it has recently been localized in human and mice pituitary, indicating a functional significance of PPARgamma in adenopituitary tumours. In the present study, we localized the PPARgamma mRNA and protein in different cell types of rat pituitary. Moreover, using the real-time polymerase chain reaction, we assessed the mRNA expression of PPARgamma in different physiological and pathological settings known to be associated with alterations in anterior pituitary cell proliferation and/or function. Our experiments have shown that PPARgamma mRNA levels were repressed by oestrogen through an oestrogen receptor-alpha effect. However, PPARgamma protein levels were only modified in males but not in females. On the other hand, PPARgamma mRNA expression was increased in dwarf rats in comparison with Lewis rats. Finally, nutritional, thyroid status or pregnancy did not change PPARgamma expression. Taken together, we provide new data regarding the regulation of pituitary PPARgamma mRNA by hormonal and metabolic status.