Progesterone-receptive dopaminergic and neuropeptide Y neurons project from the arcuate nucleus to gonadotropin-releasing hormone-rich regions of the ovine preoptic area

Progesterone inhibits gonadotropin-releasing hormone (GnRH) secretion in sheep through an interneuronal system located in the mediobasal hypothalamus. This study focused on known inhibitors of GnRH secretion in sheep, dopamine and neuropeptide Y (NPY). As the distributions of tyrosine hydroxylase (TH)- and NPY-immunoreactive neurons overlap with progesterone receptors (PR) in the arcuate nucleus, we hypothesized that, if these neurons mediate, at least partially, the inhibitory feedback signal of progesterone, then they should co-express PRs. Fluorogold (FG), a retrograde tracer, was injected into the preoptic area of ovariectomized ewes pretreated with estrogen and progesterone. When the FG injection site encompassed at least 80 GnRH neurons, sections from the arcuate nucleus were processed using dual immunocytochemistry for PR and either TH or NPY. We found that 30 of PR-immunoreactive, 12 of TH-containing and 21 of NPY-synthesizing neurons project toward this GnRH-rich region. Of the PR/TH dual-labeled cells, which represent 21 of PR and 31 of TH cells, respectively, 22 displayed FG labeling. Of the PR/NPY neurons, which account for 19 of PR and 67 of NPY neurons, respectively, 26 were FG fluorescent. This study suggests that subsets of arcuate nucleus dopaminergic and NPY neurons may transduce, at least in part, the progesterone-mediated inhibition of GnRH secretion.