RESUMEN
Previous studies have shown that oestradiol (E2) decreases the orexigenic effect of melanin-concentrating hormone (MCH). In the present study, we examined whether this action of E2 is mediated by its ability to decrease the expression of MCH or its receptor (MCHR1). Using immunocytochemistry and western blotting, we examined whether E2 decreases MCH-immunoreactive neurones or MCHR1 protein content in the hypothalamus of female rats. We found that both MCH and MCHR1 protein expression was decreased by acute E2 treatment in ovariectomised rats, and by the peri-ovulatory increase in circulating E2 in pro-oestrous rats, relative to rats at other cycle stages. To determine whether these changes in MCH/MCHR1 protein expression may be mediated by E2's ability to directly regulate the transcription of MCH and MCHR1 genes, the effect of E2 treatment on MCH and MCHR1 mRNA expression in a neuronal hypothalamic cell line was examined using real-time reverse transcriptase-polymerase chain reaction. We also determined whether MCH and oestrogen receptor (ER)α are co-expressed in the hypothalamus of female rats. E2 treatment did not decrease MCH or MCHR1 mRNA expression in vitro, and no hypothalamic neurones were identified that co-expressed MCH and ERα. We conclude that E2-dependent decreases in hypothalamic MCH/MCHR1 protein expression mediate the ability of E2 to decrease MCH-induced feeding. The current findings suggest, however, that E2 exerts these actions indirectly, most likely though interactions with other neuronal systems that provide afferent input to MCH and MCHR1 neurones.