Inhibitory effect of central ghrelin on steroid synthesis affecting reproductive health in female mice

Abstract

Ghrelin is a 28-amino acid peptide hormone that regulates ovarian steroid hormone synthesis; however, there is limited evidence regarding the regulation of this pathway by ghrelin in mice ovary. Thus, we aimed to investigate whether central ghrelin action plays a role in murine reproductive health by inhibiting steroid synthesis. Further, we sought to examine the mechanism of central ghrelin action in ovarian steroid hormone synthesis. After the administration of intracerebroventricular ghrelin (1 nmol), we found reduced serum concentrations of oestradiol and progesterone and reduced secretion of follicle-stimulating hormone and luteinising hormone. Although ghrelin reduced 3β-hydroxysteroid dehydrogenase mRNA and protein levels in the hypothalamus, it did not affect the expression of steroidogenic acute regulatory protein and cytochrome P450 17A1. In the ovary, central ghrelin regulation indirectly inhibited the mRNA and protein levels of steroidogenic acute regulatory protein, cytochrome P450 17A1, and 3β-hydroxysteroid dehydrogenase. Moreover, no changes were observed in the expression of proliferating cell nuclear antigen and phosphorylation of extracellular signal-regulated kinase. We hypothesised that central ghrelin regulation suppressed serum oestradiol and progesterone levels by indirectly inhibiting the expression of steroidogenic acute regulatory protein, cytochrome P450 17A1, and 3β-hydroxysteroid dehydrogenase in the ovary. In this regulation, the suppressed secretion of the follicle-stimulating hormone and luteinising hormone in the pituitary by ghrelin could be involved. Furthermore, hypothalamic 3β-hydroxysteroid dehydrogenase expression is reduced by ghrelin injection.