Estrogens impair hypophagia and hypothalamic cell activation induced by vasoactive intestinal peptide, but not by pituitary adenylate cyclase-activating polypeptide.

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) act in arcuate (ARC) and paraventricular (PVN) hypothalamic nuclei, reducing food intake and changing plasma parameters. Estrogens (E) also regulate energy homeostasis, and loss of ovarian function leads to hyperphagia and body weight gain. This study aimed to evaluate the effects of estradiol (E) in a postmenopausal rat model, ovariectomy (OVX), on PAC1 and VPAC2 receptors in the PVN and ARC, as well as on food intake, plasma parameters, and PVN and ARC cell activation in response to intracerebroventricular microinjection of VIP and PACAP. For this, the rats underwent intracerebroventricular and OVX surgeries, being treated daily with subcutaneous injections of 0.2 mL of corn oil or 10 μg/0.2 mL of estradiol cypionate, comprising the OVX+O and OVX+E groups, respectively. OVX+E showed reduced VPAC2 mRNA expression in the PVN. PACAP reduced food intake in both groups, and VIP-induced hypophagia was not observed in OVX+E. VIP increased plasma glucose in both groups, and PACAP increased plasma glucose only in OVX+O. VIP decreased free fatty acids in OVX+E. Furthermore, PACAP increased ARC cell activation in both groups, and in the PVN only in OVX+O. Cell activation induced by VIP in ARC and PVN was blocked by estradiol. Therefore, estrogens disrupted the hypophagia induced by VIP, but not by PACAP, and these differences seem to be, at least in part, due to an impairment of the activation of the ARC-PVN pathway.