Progestin target cell distribution in forebrain and midbrain regions of the 8-day postnatal mouse brain

Abstract

The present study investigated the anatomical distribution of progestin target cells throughout the forebrain and midbrain regions of the 8-day postnatal female mouse. Female ICR mice were sc injected with 100 μg/100 g BW estradiol valerate on postnatal day 5 (birth = day 0). On postnatal day 8, treated mice were sc injected with 0.32 μg/100 g BW (Z)-17β-hydroxy-17α-(2-[125I]iodovinyl)4-estren-3-one ([125I] progestin). For competition, additional estrogen-treated mice were each injected with 320 μg R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione; a potent synthetic progestin), 320 μg dihydrotestosterone, or 32, 160, or 320 μg corticosterone 1 h before [125I]progestin to show the specificity of [125I]progestin for the progestin receptor. Two hours after injection of [125I]progestin, the brains were removed, frozen, and processed for high resolution thaw-mount autoradiography. After 8-60 days of exposure, nuclear uptake and retention of [125I]progestin were detected in many brain regions, including the septum; bed nucleus of the stria terminalis; and preoptic area, periventricular nucleus, ventromedial nucleus, arcuate nucleus, and dorsomedial nucleus of the hypothalamus. In addition, labeling was seen in the cerebral cortex, caudate putamen, hippocampus, amygdala, and substantia nigra. Competition studies showed that excess R5020 prevented nuclear concentration of ligand, while dihydro-testosterone and corticosterone did not. The results indicate that the distribution of progestin target cells in extrahypothalamic regions of the developing brain is more extensive than that in the adult, while a similar topography was seen in the preoptic area and hypothalamus. The results further suggest that progestin action during brain development may influence the growth and development of target cells not only in the hypothalamus but also in regions of the brain previously not considered to be sites of hormone action.