Effect of inhibitor and activator of ghrelin receptor (GHS-R1a) on porcine ovarian granulosa cell functions

It was previously shown, that ghrelin and its agonistic analogue, ghrelin 1–18, can be a stimulator of ovarian cell functions (promoter of proliferation, inhibitor of apoptosis and stimulator of hormones release). The aim of our studies was to compare the action of two ghrelin analogues – ghrelin 1–18, activator of ghrelin receptors (GHS-R1a), and (d-Lys3)-GHRP-6, its inhibitor, on porcine ovarian granulosa cell functions. Effects of (d-Lys3)-GHRP-6 added at doses of 0, 1, 10 or 100 ng/ml on the expression of markers of proliferation (PCNA, cyclin B1, MAPK/ERK1,2), apoptosis (bax, p53, caspase 3) and release of steroid hormones (progesterone, testosterone, estradiol) were examined. In addition, some effect of ghrelin 1–8 on some of these parameters (expression of MAPK/ERK1,2, bax, p53) were verified. It was shown, that (d-Lys3)-GHRP-6 promotes all markers of granulosa cell proliferation, inhibits all markers of apoptosis and stimulates the release of all three steroid hormones. Similar effects of (d-Lys3)-GHRP-6 (inhibitor of GHS-R1a) and ghrelin 1–18 (its stimulator) suggest that the examined effects of these substances on porcine ovaries are not mediated by GHS-R1a. Both chemical analogues could be potentially useful for stimulation of reproductive processes, at least in in vitro conditions.

► Comparison of effect of two ghrelin analogues, ghrelin 1–18 and (D-Lys3)-GHRP-6 sowed, that ghrelin is an important regulators of basic ovarian functions (proliferation, apoptosis, and steroidogenesis). ► Comparison of effect of two ghrelin analogues, ghrelin 1–18 and (D-Lys3)-GHRP-6 sowed, that both ghrelin analogues has similar action. ► Comparison of effect of two ghrelin analogues, ghrelin 1–18 and (D-Lys3)-GHRP-6 sowed, that ghrelin action on the ovary is probably not mediated by ghrelin receptor GHS-R1a. Both chemical analogues could be potentially useful for stimulation of reproductive processes.