Estrogen plus progesterone increases progestin receptor immunoreactivity in the brain of ovariectomized guinea pigs

The goal of these experiments was to determine the number and distribution of brain cells that contain progestin receptors (PR) and to determine the effect of estrogen and estrogen plus progesterone on PR content of those cells. Ovariectomized adult female guinea pigs were treated with oil (control), or estrogen followed by oil, or estrogen followed by progesterone. As expected, only those animals treated with estrogen plus progesterone became sexually receptive. The cellular content of PR was determined using a monoclonal antibody to the receptor, and standard immunocytochemical techniques. Analysis of the PR-immunoreactive (PR-IR) cells consisted of: (1) mapping the anatomical distribution of PR-IR cells; (2) analyzing the effect of steroid hormones on PR-IR cell number, and (3) determining the effect of steroid hormones on PR immunoreactivity per cell. PR immunoreactivity was located exclusively in the nuclei of cells in the preoptic area and hypothalamus. The most dense collections of PR-IR cells were found in the preoptic area, ventrolateral nucleus of the hypothalamus, and infundibular nucleus. Estrogen caused a dramatic increase in the number of PR-IR cells in these cell groups. Sequential treatment with estrogen plus progesterone further increased PR-IR cell number, in the preoptic area by 65%, in the ventrolateral nucleus by 38%, and in the infundibular nucleus by 49%. A cell-by-cell rating of the PR immunoreactivity was carried out in these three cell groups. We found that the staining intensity across the populations of PR-IR cells was increased by estrogen and further increased by sequential estrogen plus progesterone. Alterations in cellular PR content may contribute importantly to the ability of progesterone target cell groups to perform their specialized roles in steroid-regulated activity.