No abstract

No abstract

Ghrelin, a novel growth hormone (GH)-releasing peptide, was recently isolated from the rat stomach as an endogenous ligand to growth hormone secretagogue receptor (GHS-R). Ghrelin specifically stimulates the release of GH from the rat anterior pituitary gland, but the regulational effect of ghrelin on GH secretion has not yet been clarified. We used a perifusion system to examine the single effect and combined effects of ghrelin with growth hormone-releasing hormone (GHRH) and somatostatin on GH secretion from rat anterior pituitary cells. The increase in GH concentration due to ghrelin stimulation showed a transitory peak that was almost the same as that previously reported for GHS, but apparently distinct from that of GHRH. Ghrelin (10(-10) M to 10(-8) M) stimulated GH secretion from the rat anterior pituitary cells in a dose-dependent manner. Serial ghrelin stimulation of the dispersed cells at 1-h intervals decreased the GH response, but the response recovered with stimulation at 3-h intervals, indicating that ghrelin strongly desensitized cells. Costimulation with ghrelin and GHRH elicited neither a synergistic nor an additive GH response from the rat pituitary cells. Furthermore, pretreatment to anterior pituitary cells with somatostatin strongly abolished ghrelin- and/or GHRH-stimulated GH secretion. In this study, we demonstrated that ghrelin caused weaker GH secretion than that caused by GHRH, and we also showed that costimulation with GHRH had no additive or synergistic effect on GH secretion, suggesting that ghrelin indirectly affects coordinated GH release from pituitary gland, as found in vivo.

Ghrelin was recently isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. Although it is well known that a large amount of ghrelin is produced in the gastrointestinal tract, developmental changes in ghrelin mRNA expression and differentiation of ghrelin-immunopositive (ghrelin-ip) and mRNAexpressing (ghrelin-ex) cells in the stomach have not been elucidated.In this study, we therefore investigated the changes in ghrelin mRNA expression levels and in the numbers of ghrelin-ip and -ex cells in the stomachs of 1-to 8-week-old male and female rats by Northern blot analysis, immunohistochemistry and in situ hybridization. Northern blot analysis showed that the level of weak ghrelin mRNA expression was low in the postnatal period but then increased in a dimorphic pattern, i.e. transient stagnation at 4 weeks in the male rats and at 5 weeks in the female rats. The number of ghrelin-ip and ghrelin-ex cells also increased after birth, and more numerous ghrelin cells were found in female rats than in male rats, and this finding was confirmed by Northern blot analysis. Ghrelin-ip and -ex cells first appeared in the glandular base of the fundic gland and then they were found in the glandular base and the glandular neck at 3 weeks of age, suggesting that the distribution of ghrelin cells is extended from the glandular base to the glandular neck during the postneonatal development period. This is the first report on detailed changes in postneonatal ghrelin expression level and in the number of ghrelin cells in the rat stomach. The sexual dimorphism of ghrelin expression and ghrelin cell differentiation suggest that ghrelin plays an important physiological role in the stomach.

This study was carried out to examine the developmental stage when prolactin cells differentiate in mice and to examine the effects of diethylstilbestrol on the development of prolactin cells in the fetal and neonatal pituitary glands. A small number of immunoreactive prolactin cells appeared first on embryonic day 15 in control (injected with oil) pituitary glands, whereas they did not increase in number until postnatal day 2. In diethylstilbestrol-treated mice (5 mg/kg body weight, 24 h before killing), a small number of immunoreactive prolactin cells were detectable as early as embryonic day 14, but not on day 13. They increased in number on embryonic days 15 and 16, and decreased markedly on days 17 and 18, followed by a rapid increase after birth. This transient reduction in the response to diethylstilbestrol was partially restored by treatment with metyrapone, a specific inhibitor of corticosteroid production. These results suggest that in the mouse: (1) differentiation of prolactin cells occurs between embryonic days 13 and 14, (2) prolactin gene expression is suppressed in the nascent prolactin cells presumably due to the presence of high levels of estrogen-binding protein, alpha-fetoprotein, and (3) prolactin gene expression is also suppressed by elevation of circulating glucocorticoids during the perinatal period. The present results suggest that, in the mouse, at least a proportion of prolactin cells are not derived from growth hormone cells, because the diethylstilbestrol-induced prolactin cells appear earlier than growth hormone gene expression.