| Neuropeptide Y (NPY) is an important regulator of many neuroendocrine processes, including reproduction. Reproduction is under the control of the hypothalamic-pituitary-gonadal axis, and NPY actions in both the hypothalamus and the pituitary are critical for its proper functioning. On the afternoon of proestrus, NPY, via activation of Y1 receptors (Y1r) stimulates gonadotropin-releasing hormone (GnRH) release from the hypothalamus and enhances the ability of GnRH to stimulate LH release from gonadotropes in the pituitary, producing the LH surge that evokes ovulation on the following morning. Given this importance of the Y1r, these studies examined Y1r expression, regulation, and function in the hypothalamus and pituitary of female rats. Results indicate that neurons co-expressing Y1r and estrogen receptor ERalpha were in the medial preoptic area (MPA) and arcuate nucleus, while Y1r-ERbeta co-expressing neurons were in the MPA, supraoptic nucleus and paraventricular nucleus. Changes in hypothalamic Y1r protein with varying estrogen levels during the estrous cycle were not detected. Importantly, Y1r immunoreactivity was present in GnRH nerve terminals. Y1r gene expression in the pituitary was negatively regulated by estrogen, accounting for low receptor levels on proestrus and increased expression on estrus. Blockade of Y1r on proestrus delayed expected LH and prolactin surges, as well as attenuated the LH surge. Consistent with the hypothesis that NPY activates Y1r directly on the gonadotropes and lactotropes, both cell types contained Y1r immunoreactivity. This Y1r immunoreactivity was localized with the Golgi protein TGN38. Negative energy balance due to 48-hour fast suppressed LH secretion and decreased Y1r immunoreactivity in the arcuate nucleus of the hypothalamus, but pituitary Y1r mRNA levels were unchanged. Thus, information about metabolic state is likely processed at the hypothalamic level of the reproductive axis. These studies highlight the importance of Y1 receptors in the regulation of reproductive hormone secretion and present new information about localization of the receptors within specific cell types in the hypothalamus (GnRH nerve terminals), and the pituitary (gonadotropes and lactotropes). The results encourage future studies focusing on Y1r trafficking and signaling, as well as interactions between energy and reproductive systems. |
