Ontogeny of Region-Specific Sex Differences in Androgen Receptor Messenger Ribonucleic Acid Expression in the Rat Forebrain

Abstract

Testosterone and its metabolites are the principal gonadal hormones responsible for sexual differentiation of the brain. However, the relative roles of the androgen receptor (AR) vs. the estrogen receptor in specific aspects of this process remain unclear due to the intracellular metabolism of testosterone to active androgenic and estrogenic compounds. In this study, we used an 35S-labeled riboprobe and in situ hybridization to analyze steady state, relative levels of AR messenger RNA (mRNA) expression in the developing bed nucleus of the stria terminalis, medial preoptic area, and lateral septum, as well as the ventromedial and arcuate nuclei of the hypothalamus. Each area was examined on embryonic day 20 and postnatal days 0, 4, 10, and 20 to produce a developmental profile of AR mRNA expression. AR mRNA hybridization was present on embryonic day 20 in all areas analyzed. In addition, AR mRNA expression increased throughout the perinatal period in all areas examined in both males and females. However, between postnatal days 4 and 10, sharp increases in AR mRNA expression in the principal portion of the bed nucleus of the stria terminalis and the medial preoptic area occurred in the male that were not paralleled in the female. Subsequently, males exhibited higher levels of AR mRNA than females in these areas by postnatal day 10. There was no sex difference in AR mRNA content in the lateral septum, ventromedial nucleus, or arcuate nucleus at any age. These results suggest that sex differences in AR mRNA expression during development may lead to an early sex difference in sensitivity to the potential masculinizing effects of androgen.

Sex differences in the distribution of androgen receptors in the human hypothalamus

“…All of these data, taken together, indicate that various AR antibodies reveal a similar AR-ir in the brain of each species. It should be noted that the immunohistochemical distribution of AR, as indicated by the present study, in general, agrees well with that revealed by autoradiography in the rat and monkey brain (with tritiated testosterone or tritiated dihydrotestosterone; Clancy et al, 1992), with in situ hybridization studies in the rat brain (Simerly et al, 1990;McAbee et al, 1998), and with PG21 staining results in the Syrian hamster brain (Wood and Newman, 1999), the ferret brain (Kashon et al, 1996), and the monkey brain (Wu et al, 1995).…”

Estrogen Receptor Immunoreactivity in Late-Gestation Fetal Lambs1

“…Similar findings have been reported in rats [60,61]. By contrast, sex differences in AR immunoreactivity favor males, with increased levels of AR mRNA and protein in MPOA and BST of male sheep [62], hamsters [63], rats [64], and mice [65]. Similar sex differences in AR were not identified in human brain [66].…”

Cellular phenotype of androgen receptor‐immunoreactive nuclei in the developing and adult rat brain

“…In addition, AR mRNA expression was found in similar hypothalamic, limbic, and cortical structures as well as in the thalamus and the ventral horn of the spinal cord of adult male and female rats (Simerly et al, 1990). AR mRNA expression was also observed, in the same pattern of distribution, throughout the forebrain of developing male and female rats (McAbee and DonCarlos, 1998). In these studies, the cellular phenotype of AR-expressing cells was not explored.…”