RESUMEN
Kisspeptin/metastin has been implicated as a critical regulator in luteinizing hormone (LH) secretion and the reproductive system mediating the effect of estrogen on GnRH neurons. In the present study we examined the sex differences in the effects of estrogen on Kiss1/kisspeptin expression in the forebrain by using gonadectomized rats to assess the interaction of kisspeptin and GnRH neurons. Kiss1/kisspeptin cell bodies were abundant in the rostral periventricular area of the third ventricle (RV3P) and the arcuate nucleus (ARC). A few cell bodies were also observed in other portions of the forebrain, i.e. the bed nucleus of the stria terminalis (BST), the paraventricular hypothalamic nucleus (PaAP), the ventromedial hypothalamic nucleus (VMH), and the medial amygdaloid nucleus (MeA). Kisspeptin-immunoreactive fibers were found mainly in the median eminence (ME), the ARC, and the RV3P, but were scarce in the preoptic area (POA), where GnRH neurons are localized. We also found that estrogen triggers expression of the Kiss1 gene and peptide within all the regions except the ARC, and that the effects in the RV3P, BST, PaAP, and VMH are greater in estrogen treated ovariectomized female rat. It is noteworthy that kisspeptin and GnRH neurons were densely associated in the ME but were rarely in contact in the POA. Thus, our results suggest that kisspeptin-positive neurons, except for the ones in the ARC, are related not only to estrogen-positive feedback, but also sex dimorphism, and that kisspeptin regulates GnRH release in the ME rather than the POA.
Asunto(s)
Estradiol/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Prosencéfalo/metabolismo , Animales , Núcleo Arqueado del Hipotálamo/citología , Núcleo Arqueado del Hipotálamo/metabolismo , Femenino , Regulación de la Expresión Génica , Inmunohistoquímica , Kisspeptinas/genética , Masculino , Eminencia Media/citología , Eminencia Media/metabolismo , Neuronas/citología , Orquiectomía , Especificidad de Órganos , Ovariectomía , Prosencéfalo/citología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Caracteres Sexuales , Tercer Ventrículo/citología , Tercer Ventrículo/metabolismoRESUMEN
The expression of Kiss1 in the anteroventral periventricular nucleus (AVPV) and its product, metastin/kisspeptin, show a circadian pattern with a peak in the evening, which shows a strong phase relationship with the time of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) surge in rodents. Here we report that a circadian transcriptional factor, albumin D-site binding protein (Dbp), was able to trigger mKiss1 transcription via the D-box, and this effect was combined with those of estrogen receptor α (ERα) and its ligand, estrogen. A histological study demonstrated that some cells in the AVPV co-expressed Dbp with ERα in adult female rats. Expression of ERα was not rhythmic in the AVPV, however, mRNA of Dbp in the AVPV accumulated with a robust diurnal rhythm in proestrus, but not on the first day of diestrus. Thus, these results suggest that Dbp and estrogen regulate the expression of Kiss1 in the AVPV, thereby mediating the GnRH/LH surge.