Progesterone receptor, estrogen receptor alpha, and the type II glucocorticoid receptor are coexpressed in the same neurons of the ovine preoptic area and arcuate nucleus: a triple immunolabeling study.

The neuroendocrine reproductive and stress axes are known to be closely linked, but the mechanisms underlying these links remain poorly understood. In the ovine brain, GnRH neurons do not contain type II glucocorticoid (GR), progesterone (PR), or alpha estrogen (ERalpha) receptors. We sought to determine whether PR, ERalpha, and GR coexist within the same hypothalamic neurons. A triple immunocytochemical study, involving antisera raised in three different species, was performed on cryostat sections from ovariectomized ewes treated either with estradiol and progesterone or with progesterone alone. All PR-immunoreactive neurons contained ERalpha, and about 95% of ERalpha were PR immunoreactive in the preoptic area and arcuate nucleus. Although the PR with ERalpha colocalization ratio was not affected by the steroid treatments, immunolabeling for PR was weaker in animals that did not receive estradiol. Numerous PR- and ERalpha-immunoreactive cells contain GR. PR+ERalpha+GR-immunoreactive cells represent 70% of PR, 65% of ERalpha, and 72% of GR in the preoptic area and 70% of PR, 66% of ERalpha, and 63% of GR in the arcuate nucleus. These results suggest that estrogen, progesterone, and glucocorticoids may influence the activity of the same neurons to modulate both reproductive and stress axes.