Fluctuating estrogen and progesterone receptor expression in brainstem norepinephrine neurons through the rat estrous cycle

Norepinephrine (NE) neurons within the nucleus tractus solitarii (NTS; A2 n eurons) and ventrolateral medulla (A1 neurons) represent gonadal steroid-de pendent components of several neural networks regulating reproduction. Prev ious studies have shown that both A1 and A2 neurons express estrogen recept ors (ERs). Using double labeling immunocytochemistry we report here that su bstantial numbers of NE neurons located within the NTS express progesterone receptor (PR) immunoreactivity, whereas few PRs are found in ventrolateral medulla. The evaluation of ER alpha and PR immunoreactivity in NE neurons through the estrous cycle revealed a fluctuating pattern of expression for both receptors within the NTS. The percentage of A2 neurons expressing PR i mmunoreactivity was low on metestrus and diestrus (3-7%), but increased sig nificantly to approximately 24% an proestrous morning and remained at inter mediate levels until estrus. The pattern of ER alpha immunoreactivity in A2 neurons was more variable, but a similar increment from 11% to 40% of NE n eurons expressing ER alpha was found from diestrus to proestrus. Experiment s in ovariectomized, estrogen-treated and estrogen-plus progesterone-treate d rats revealed that PR immunoreactivity in A2 neurons was induced strongly by estrogen treatment, whereas progesterone had no significant effect. The numbers of ER alpha-positive NE neurons were not influenced by steroid tre atment. These observations provide direct evidence for PRs in NE neurons of the brainstem and show that cyclical patterns of gonadal steroid receptor expression exist in A2, but not A1, neurons through the rat estrous cycle. The expression of PR in A2 neurons appears to be driven principally by circ ulating estrogen concentrations. The fluctuating levels of ER alpha and PR expression in these brainstem NE neurons may help generate cyclical pattern s of biosynthetic and electrical activity within reproductive neural networ ks.