Effects of intracerebroventricular ghrelin on food intake and Fos expression in the arcuate nucleus of the hypothalamus in female rats vary with estrous cycle phase

摘要

Intracerebroventricular (icv) injection of ghrelin increases food intake via activation of neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons, which express growth hormone secretagogue receptor type 1a (GHS-R1a), in the arcuate nucleus of the hypothalamus (Arc) in male rats. Conversely, elevation in endogenous estrogens or exogenous estrogens decreases food intake, but the precise mechanism mediating this estrogenic effect is unknown. We studied whether the effects of icv ghrelin on food intake and on the expression of Fos, a marker of neuron activation, vary with estrous cycle phase in female rats. Icv ghrelin (100. pmol) significantly increased food intake after injection in diestrus, but it did not affect food intake in proestrus during light phase. Icv ghrelin increased the number of Fos-positive neurons in the Arc both in proestrus and diestrus; however, a significantly larger number of Fos-positive neurons appeared in diestrus than in proestrus. Real-time RT-PCR analysis showed no significant difference in GHS-R1a mRNA expression levels in the mediobasal hypothalamus between diestrus and proestrus. These results indicated that not only the orexigenic effect but also the Fos-inducing effect of icv ghrelin were influenced by the estrous cycle phase; and both effects were reduced in proestrus but not in diestrus. Most NPY/AgRP neurons seemed to be influenced indirectly by estrogens during proestrus because only a few of the NPY/AgRP neurons present in the Arc express ERα. The change in GHS-R1a expression levels in the hypothalamus during estrous cycle is not probably involved in the estrous cycle-induced changes in ghrelin action because there was no difference in GHS-R1a mRNA expression between diestrus and proestrus.