Regulation of androgen receptor messenger ribonucleic acid expression in the developing rat forebrain.

Abstract

By postnatal day 10 (PND-10), males express more androgen receptor (AR) messenger RNA (mRNA) than females in the principal portion of the bed nucleus of the stria terminalis (BSTpr) and medial preoptic area (MPO), but not in the ventromedial hypothalamus. The development of these region-specific sex differences in AR mRNA expression may be critical for the organization of male-typical neural circuitry and may represent the onset of sex differences in the sensitivity of the rat brain to the actions of androgens. In this study, we used a 35S-labeled riboprobe and in situ hybridization to address whether postnatal testosterone exposure is important for the up-regulation of AR mRNA content in the developing rat forebrain. In the BSTpr and the MPO of PND-10 rats, males gonadectomized on PND-0 or PND-5 had lower levels of AR mRNA compared with intact or sham-operated control males. Daily replacement of testosterone to animals gonadectomized on PND-0 maintained AR mRNA content in the BSTpr and the MPO at levels equal to those in intact males. In contrast, there was no effect of gonadectomy or testosterone replacement on AR mRNA expression in the ventromedial hypothalamus. Thus, the postnatal hormonal environment may permit the development of region-specific sex differences in AR mRNA. Significant alterations in AR mRNA expression in the BSTpr and MPO in PND-10 male rats were induced by gonadectomy as late as PND-8. Males gonadectomized on PND-8 had levels of AR mRNA significantly lower than those in intact males, but significantly higher than those in intact females. Further, when animals were gonadectomized on PND-0 and given testosterone on PND-8 and PND-9, levels of AR mRNA were also intermediate between those found in intact males and intact females. The exact time course for transcriptional regulation of AR mRNA in the developing rat brain is unknown. However, others have shown significant regulation of AR mRNA within hours of hormone treatment, so that 2 days of hormone withdrawal or replacement are probably sufficient to achieve new steady state levels of message. Moreover, sexually dimorphic neuronal loss has been documented to peak in hypothalamic cell groups during the first postnatal week. Thus, it is likely that changes in the number of AR mRNA-expressing cells as well as the amount of AR mRNA expression per cell are responsible for the development of male-typical AR mRNA content.