Montserrat Blanco

Ghrelin, A Novel Placental-Derived Hormone1

Ghrelin, a GH-releasing acylated peptide, has been recently identified from the rat stomach. The purified peptide consists of 28 amino acids in which the serine 3 residue is n-octanoylated. Here we show that ghrelin messenger RNA and ghrelin peptide are present in the human as well as in rat placentae. In human placenta, ghrelin was detected by PCR at both first trimester and after delivery. While ghrelin was not detected by immunohistochemistry in human placenta at term, it was easily identified by immunohistochemistry at first trimester being mainly expressed in cytotrophoblast cells and scarcely in syncytiotrophoblast ones. Ghrelin was also identified in a human choriocarcinoma cell line, the BeWo cells. Ghrelin was found, by immunohistochemistry, in the cytoplasm of labyrinth trophoblast of rat placenta, whereas other placental cell types seems to be negative for ghrelin immunostaining. Moreover, placental ghrelin messenger RNA, in pregnant rats, showed a characteristic profile of expression being practically undetectable during early pregnancy, with a sharp peak of expression at day 16 and decreasing in the latest stages of gestation. In conclusion, ghrelin has been detected in human and rat placenta showing a pregnancy-related time course of expression. Whether placenta-derived ghrelin is involved in the modulation of GH release, or placental cell growth and differentiation remains to be established.

Cellular localization of orexin receptors in human adrenal gland, adrenocortical adenomas and pheochromocytomas

Orexin-A and -B are hypothalamic peptides derived from a precursor called prepro-orexin and related with the regulation of the energy balance and arousal. They act on G protein receptors named orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). In the present study, we used immunohistochemical techniques to detect the distribution of OXR in normal human adrenal gland and adrenal tumours (adrenocortical adenomas and pheochromocytomas). OX1R was expressed in the cortex of the normal human adrenal gland (glomerulosa, fasciculata and reticular zones) and OX2R was located in the medulla (epinephrine and norepinephrine cells). By the double immunofluorescence techniques, we demonstrated that virtually all medullar cells (epinephrine and norepinephrine cells) expressed OX2R. As was expected, according to the results obtained in normal tissues, cortical tumours (adrenocortical adenomas) were positive for OX1R but not for OX2R and conversely, medullar tumours (pheochromocytomas) expressed only OX2R.

Merkel cells, a new localization of prepro-orexin and orexin receptors

Orexins (OXA and OXB) are peptides derived from a common precursor called prepro‐orexin. They act through G‐protein receptors named orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). Orexins were first demonstrated in neurons of the lateral hypothalamus and found to be related to the control of food intake. However, it has been shown that they are widely distributed in both the nervous system and peripheral tissues, including endocrine organs such as the pituitary and adrenal glands. Merkel cells are neuroendocrine cells situated in the epidermis, tactile hairs and oral mucosa, and act as mechanoreceptors. Up to the present, various neuropeptides have been detected in these cells. The aim of the present study was to detect the presence of prepro‐orexin and orexin receptors (OX1R and OX2R) in porcine Merkel cells using immunohistochemistry. Prepro‐orexin was expressed in the cytoplasm of Merkel cells in the skin of the pig snout. Immunoreactivity for prepro‐orexin was more intense in the mature side of the cell, where the dense‐cored granules are accumulated. Epidermal nerve terminals associated with Merkel cells and dermal nerve fibres showed no immunostaining. Both orexin receptors (OX1R and OX2R) were also demonstrated in the cytoplasm of Merkel cells of pig snout skin. The finding of orexins and their receptors in Merkel cells suggests that they have an autocrine function. Further studies are needed to ascertain the significance of this function.

Cellular and Subcellular Distribution of 7B2 in Porcine Merkel Cells

ABSTRACT Background: Merkel cells are neuroendocrine cells located in the skin and oral mucosa of various mammalian species. These cells express multiple peptides as well as serotonin. Although the precise function of Merkel cells is still unknown, different studies support its role as mechano‐electric transducer. 7B2 granin (secretogranin V) is a polypeptide isolated from the pituitary gland and present in the dense‐cored granules of neuronal and paraneuronal cells.

Cellular Localization of Prepro-Orexin and Orexin Receptors (Ox1R and Ox2R) in Merkel Cells

Orexins (A and B) were first demonstrated in neurons of the lateral hypothalamus, both peptides derived from a common precursor called prepro-orexin. Orexins act through previously orphan G-protein receptors named orexin receptor 1 (Ox1R) and orexin receptor 2 (Ox2R). Up to the present, various neuropeptides have been detected in neuroendocrine cells of the skin (Merkel cells). The aim of our study was to investigate the presence of orexin receptors and prepro-orexins in Merkel cells. Immunohistochemical techniques were performed to detect preproorexin and orexin receptors (Ox1R and Ox2R) in human and porcine Merkel cells. Prepro-orexin was expressed in the cytoplasm of Merkel cells of pig snout skin and human fingertip. Immunoreactivity for prepro-orexin was more intense in the mature side of the Merkel cell. Epidermal nerve terminals associated with Merkel cells and dermal nerve fibers showed no immunostaining. Orexin receptors were also demonstrated in the Merkel cells of pig snout skin. Further studies must be followed to ascertain the role that orexins play in cutaneous neuroendocrine cells.