Hormonal regulation of androgen receptor messenger RNA in the medial preoptic area of the male rat

In the adult male rat, androgen and estrogen synergize in the regulation of male reproductive behaviors. To explore some of the molecular mechanisms underlying this synergism we examined the distribution and hormonal regulation of androgen receptor (AR) and estrogen receptor (ER) mRNAs in the medial preoptic area (MPOA) and bed nucleus of the stria terminalis (BST) of the adult male rat. Using in situ hybridization, AR and ER mRNAs were found to be distributed in overlapping but unique patterns. The highest density of AR mRNA was found in the central part of the medial preoptic n, and the principal n. of the BST. Gonadectomy (GDX) of adult male rats caused an increase in hybridization density in both brain areas after 4 days followed by a decrease after 2 months. in contrast, ER mRNA was increased following GDX and remained high regardless of length of time. Treatment of adult GDX'd males with dihydrotestosterone (DHT) reversed the effects of GDX on AR mRNA at both the short and long-term castrate bur had no effect on ER mRNA in both the MPOA and BST. Estrogen treatment increased AR mRNA in the long-term castrate only and decreased ER mRNA in both long- and short-term castrates. Immunocytochemical detection of AR revealed a similar distribution to AR mRNA; however, AR immunoreactivity was reduced in the MPOA and BST after both short- and long-term GDX. In vitro [H-3]DHT binding in cytosols of the preoptic area showed appreciable binding but there was no effect of length of time following GDX. These data show that the pattern of regulation of AR mRNA is unique to this receptor type and does not follow the pattern of regulation of the ER mRNA. Furthermore, although the distribution of AR mRNA and AR protein coincide within the MPOA, changes in mRNA levels as a result of castration or hormone treatment do not result in corresponding changes in binding. This mismatch between mRNA and binding suggests a complex regulation of AR beyond simply changes in transcription.