Impact Of Ghrelin On Food Intake And Steroid Hormone Synthesis In Mice

Ghrelin is an orexigenic agonist that acts directly on neurons in the hypothalamus,controlling murine feeding circuits and reward-based hedonic eating behaviors Meanwhile,it also regulates gonadotropin secretion and may influence the timing of puberty via hypothalamic.Here,we sought to examine the mechanism of ghrelin action in food intake and ovarian steroid synthesis in the hypothalamus.After the administration of peripheral ghrelin(50 μg/kg)in mice,ghrelin stimulation activated estrogen receptor alpha(ERα)-expressing neurons during the estrous cycle and that agouti-related peptide(Ag RP)m RNA expression was remarkably increased.Moreover,the response of oxytocin(OXT)-positive neurons to ghrelin was suppressed in the proestrus period,while ghrelin also decreased the serum concentration of estradiol.By intracerebroventricular administrated(1 nmol),we found reduced serum concentrations of oestradiol and progesterone and reduced secretion of follicle-stimulating hormone and luteinising hormone.Although ghrelin reduced3β-hydroxysteroid dehydrogenase(3β-HSD)m RNA and protein levels in the hypothalamus,it did not affect the expression of steroidogenic acute regulatory protein(St AR)and cytochrome P450 17A1(CYP17A1).In the ovary,central ghrelin regulation indirectly inhibited the m RNA and protein levels of St AR,CYP17A1,CYP19A1 and3β-HSD.Moreover,no changes were observed in the expression of proliferating cell nuclear antigen and phosphorylation of extracellular signal-regulated kinase.Therefore,peripheral ghrelin may suppress oxytocin-positive neuron expression via the arcuate nucleus ERα and Ag RP neurons involved female mice food intake.Centrl ghrelin regulation in hypothalamus suppressed serum oestradiol and progesterone levels by indirectly inhibiting the expression of steroid synthesis related enzymes in the ovary.