Ontogeny of androgen receptor expression in the ovine fetal central nervous system and pituitary

In fetal sheep, circulating androgens influence fetal stress responsiveness and the timing of parturition. Nevertheless, little is known about the presence and development of androgen receptors (ARs) in the fetal brain. The present study was undertaken to test the hypothesis that expression of androgen receptor occurs in fetal brain and pituitary, and that the abundance of the AR is ontogenetically regulated. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brainstem in fetal sheep that were 80, 100, 120, 130, and 145-day gestation, and 1 and 7 days postnatal (n=4-5 per group). Using real-time RT-PCR, we measured mRNA expression levels of the receptor in these brain regions and pituitary. In a separate study, we isolated protein from the same brain regions in fetal sheep that were 80 (n=3), 120 (n=4), and 145 (n=4) days. AR mRNA expression in hypothalamus increased in late gestation, starting at 145 days, and increasing progressively after birth. A trend of increasing AR protein in hypothalamus was not significant. AR mRNA expression in pituitary was elevated after 80 days gestation, but with no further increases or decreases in late gestation, while AR protein increased significantly at the end of gestation. In hippocampus and brainstem AR mRNA was constant throughout the latter half of gestation, and AR protein was below the sensitivity of our Western blot assay. We conclude that the fetal brain and pituitary are target sites for circulating androgens or androgen precursors in fetal plasma, and we speculate that the increase in hypothalamic action of androgens immediately prior to birth might be integral to the timing of parturition.