Inhibitory Effect of Submaximal Doses of Ghrelin on Gonadotropin Secretion in Women

Abstract

The effect of ghrelin on gonadotropin secretion has been equivocal. Recent data have shown an inhibitory effect of repeated injections of ghrelin on nocturnal LH and FSH secretion in women. The aim of this study was to investigate the effect of submaximal doses of ghrelin on the diurnal secretion of gonadotropins. Ten normally cycling women received 2 consecutive dosages of ghrelin (0.15 μg/kg and 0.30 μg/kg) intravenously in the early and late follicular phases of the cycle. Saline was injected in the preceding cycle. Blood samples in relation to ghrelin or saline administration (time 0 and 90 min) were taken at -15, 0, 30, 90, 120, 150, and 180 min. Serum estradiol concentrations were significantly higher in the late than in the early follicular phase. Following ghrelin administration, serum LH and FSH levels decreased significantly, in relation to the saline injection, in the late (p<0.01), although FSH values showed a within the group decrease also in the early follicular phase (p<0.05). The study suggests a differential action of ghrelin on diurnal gonadotropin secretion throughout the follicular phase of the cycle.

Submaximal doses of ghrelin do not inhibit gonadotrophin levels but stimulate prolactin secretion in postmenopausal women

“…The present study demonstrates that the exogenous administration of two small dosages of ghrelin to postmenopausal women did not affect the secretion of FSH and LH in the context of experiments lasting for 3 hours. This is in contrast to previous studies in normally menstruating women demonstrating an inhibitory action of ghrelin on the two gonadotrophins . As in the previous experiments the degree of inhibition was greater in the late than in the early follicular phase, it was suggested that oestradiol may have a permissive action on ghrelin's effect .…”

“…In particular, the administration of ghrelin at the dose of 50 μg/h for 4 hours over midnight resulted in a significant reduction in serum FSH and LH levels . Similarly, a significant decrease in serum FSH and LH concentrations was observed during the day, when two smaller dosages of ghrelin (0.15 and 0.30 μg/kg) were injected iv 60 minutes apart to normal women in late morning …”

“…The results of these two studies have suggested that the pattern of ghrelin administration (multiple vs single dosage) may have a significant impact on the action of this hormone on gonadotrophin secretion . It has been also suggested that there may be a facilitating action of oestrogen on ghrelin‐induced gonadotrophin suppression, as this was particularly evident in the late as compared to the early follicular phase . These studies were performed in the follicular phase of the normal menstrual cycle, but the effect of ghrelin on gonadotrophin secretion in women with nonfunctioning ovaries, such as after menopause, has not been investigated.…”

Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

“…For example, the KGN cell line used in this study was originally from a 63-years old woman [69] and thus it may not represent the same granulosa cells from the other aged ovaries. Regardless, in addition to our current findings of ghrelin in ovarian inflammation, previous studies have already revealed various impacts of ghrelin in the reproductive system [19,20,21,22,23,24,25,26,27]. Thus, there is a possibility that ghrelin administration might be a potential strategy to treat inflammation-related diseases in reproductive tissues.…”

“…In fact, blood ghrelin can be regularly detected in the women receiving in vitro fertilisation (IVF) procedure [20]; Ghrelin was previously shown to stimulate prolactin secretion in normal women [21]. The submaximal dose of ghrelin was not able to induce growth hormone secretion [22], but was able to suppress gonadotropin secretion in women [23]. Human ghrelin was also demonstrated to reduce the pituitary response to gonadotropin-releasing hormone (GnRH) in superovulated ewes [24].…”