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.
Asunto(s)
Estradiol/farmacología , Hormonas Hipotalámicas/metabolismo , Hipotálamo/efectos de los fármacos , Melaninas/metabolismo , Hormonas Hipofisarias/metabolismo , Receptores de la Hormona Hipofisaria/metabolismo , Animales , Secuencia de Bases , Cartilla de ADN , Receptor alfa de Estrógeno/fisiología , Estro , Femenino , Hormonas Hipotalámicas/genética , Hipotálamo/metabolismo , Melaninas/genética , Hormonas Hipofisarias/genética , Ratas , Ratas Long-Evans , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de la Hormona Hipofisaria/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Reports that protein kinase C is inhibited by sphingosine and other long-chain amines and the suggestion that promotion of mammary carcinogenesis by dietary fat is mediated by protein kinase C prompted us to investigate the effects of a long-chain amine, 1-octadecylamine, on mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in rats fed a high-fat diet. Rats fed the amine sulfate at a level of 0.01% in a semipurified diet containing 20% corn oil developed more tumors than those fed the high-fat diet alone, although body weight gain was inhibited slightly. Rats fed the amine sulfate at 0.1% of the diet developed very few tumors compared with those fed either the high-fat diet or a low-fat diet containing 5% corn oil. At the higher level, the C18 amine also caused a marked inhibition of body weight gain.