Figure 4.

Differential regulation and activation of PR across brain regions creates a working model for the actions of P and PR within the MPN and cortex of fetal and neonatal rats. In the MPN of males, testosterone (T), secreted by the fetal and neonatal testes, readily enters the brain, in which it can be aromatized to estradiol (E) or reduced to dihydrotestosterone (DHT). Estradiol activates ERα, which increases the transcription of the PR gene. This results in a developmental period between E18 and approximately postnatal d 10 when PR expression is high in males but not females. P may arise from one or more potential sources creating brain concentrations of P that are dynamic and perhaps locally quite high. P presumably activates PR, which as a transcription factor can initiate a cascade of molecular and cellular events, which, because they occur in the male brain only, lead to sexual differentiation of MPN structure and function. In contrast, PR is expressed in an anatomically and developmentally specific manner in both male and female fetuses and neonates. PR expression in cortex is not regulated by either androgens or estradiol but rather appears to be dependent on maternal thyroid status; expression of PR in developing cortex is reduced by maternal hypothyroidism. P, likely arising from de novo synthesis in cortex, activates PR. Because PR is expressed in cortical subplate neurons and pyramidal cell layers 5 and 2 and 3, it is possible that PR plays an important role in establishing normal thalamocortical connectivity. AR, Androgen receptor; TH, thyroid hormone; THR, thyroid hormone receptor.