RESUMEN
Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites of action of orexin A in the regulation of LH release have been investigated in vivo in ovariectomized rats that were given vehicle or estradiol benzoate (EB), with or without an injection of progesterone 48 h later. Orexin A was administered intrahypothalamically under Saffan anesthesia, 50 h after the EB or vehicle; its effects on plasma LH levels were monitored in sequential blood samples. Orexin A (1.0 microg/side) injected into the rostral preoptic area (rPOA) at the level of the organum vasculosum of the lamina terminalis had a stimulatory effect on LH release in EB-treated ovariectomized rats. When orexin A was injected into the medial POA (mPOA) or the arcuate/median eminence, it had an inhibitory effect on the LH surge that occurs in ovariectomized rats primed with EB plus progesterone. Orexin A injected into the mPOA also reduced LH levels in ovariectomized rats untreated with ovarian steroids. Both the stimulatory and inhibitory effects of orexin A were antagonized by SB334867A, a selective orexin 1 receptor antagonist. Furthermore, when given alone into the rPOA, this antagonist attenuated the LH surge induced by EB plus progesterone. Thus, orexin appears to have a dual effect on LH release, being stimulatory in the rPOA and inhibitory in the mPOA or arcuate/median eminence. Both effects may be mediated, at least in part, by the orexin 1 receptor. Double label immunohistochemistry revealed close appositions between orexin A immunoreactive varicosities and a small proportion of GnRH cell bodies in the rPOA. It is suggested that the stimulatory effect of orexin A on LH release may involve direct actions on GnRH neurons.
Asunto(s)
Proteínas Portadoras/farmacología , Estradiol/análogos & derivados , Péptidos y Proteínas de Señalización Intracelular , Hormona Luteinizante/metabolismo , Neuropéptidos/farmacología , Área Preóptica/efectos de los fármacos , Área Preóptica/metabolismo , Urea/análogos & derivados , Animales , Benzoxazoles/farmacología , Proteínas Portadoras/metabolismo , Células Cultivadas , Estradiol/farmacología , Femenino , Hormona Liberadora de Gonadotropina/metabolismo , Inmunohistoquímica , Microinyecciones , Naftiridinas , Neuropéptidos/metabolismo , Receptores de Orexina , Orexinas , Ovariectomía , Área Preóptica/citología , Progesterona/farmacología , Ratas , Ratas Wistar , Receptores Acoplados a Proteínas G , Receptores de Neuropéptido/antagonistas & inhibidores , Urea/farmacologíaRESUMEN
Changes in metabolic state, such as those induced by fasting, have profound effects on reproduction. In rats, the time-course over which fasting inhibits luteinising hormone (LH) release is reduced to 48 h by the presence of oestradiol-17beta (E(2)). Hypothalamic kisspeptin plays a key role in mediating the actions of E(2) on gonadotrophin-releasing hormone (GnRH) neurones, and thereby promotes LH release. KiSS-1-expressing neurones are found in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Extensive evidence implicates the AVPV in GnRH release and the ARC in energy balance. The latter nucleus also contains neurones that express neuropeptide Y (NPY), an orexigenic peptide implicated in GnRH control. To elucidate the involvement of kisspeptin and/or NPY in hypothalamic responses to fasting, their expression was quantified by in situ hybridisation histochemistry in ovariectomised rats, with or without E(2) replacement, before and after 48 h of fasting. In the presence of E(2), but not in its absence, the fasting suppressed plasma LH. In the AVPV, the low level of KiSS-1 expression found in the absence of E(2) was unaffected by fasting. By contrast, the elevated level found in the presence of E(2) was suppressed by fasting. Independent of E(2), fasting had no effect on KiSS-1 expression in the ARC, but increased NPY expression at that site. The present study has identified the AVPV as a site at which KiSS-1 expression can be influenced by fasting. The results suggest that inhibition of KiSS-1 expression in the AVPV may be a significant factor in restraining the gonadotrophic axis in response to negative energy balance in the presence of oestrogen. The extent to which the concurrent rise in NPY expression in the ARC may contribute to the suppression of LH release by influencing AVPV kisspeptin neurones, directly or indirectly, or by actions independent of kisspeptin, remains to be established.
Asunto(s)
Núcleos Talámicos Anteriores/metabolismo , Núcleo Arqueado del Hipotálamo/metabolismo , Ayuno/fisiología , Neuropéptido Y/genética , Proteínas/genética , Animales , Peso Corporal/fisiología , Regulación hacia Abajo/genética , Ayuno/sangre , Ayuno/metabolismo , Femenino , Kisspeptinas , Hormona Luteinizante/sangre , Neuronas Aferentes/metabolismo , Neuropéptido Y/metabolismo , Proteínas/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
Among Inuit less than 30 years old the prevalence of myopia is far in excess of that of their elders. This is especially true for females. There seems to be little, if any, genetic contribution to this "epidemic" of myopia in the young. The age and sex distribution indicates the likelihood of an environmental factor, probably cultural, being responsible for the current pattern. Other data implicate school attendance as a possible etiologic factor.