Region‐specific expression and sex‐steroidal regulation on aromatase and its mRNA in the male rat brain: Immunohistochemical and in situ hybridization analyses

Abstract

The brain has an estrogen-biosynthetic potential resulting from the presence of neuronal aromatase, which controls the intraneural sex-steroidal milieu and is involved in brain sexual differentiation, psychobehavioral regulation, and neuroprotection. In the rat brain, three distinct aromatase-P450-immunoreactive (AromP450-I) neural groups have been categorized in terms of their peak expression time (fetal, fetoneonatal, and young-to-adult groups), suggesting the presence of region-specific regulation on brain AromP450. In the present study, we compared the expressions between AromP450 protein and mRNA by using immunohistochemistry and in situ hybridization with an ovary-derived cRNA probe in serial sections of fetal, fetoneonatal, and adult male rat brains and then performed steroidal manipulations to evaluate the sex-steroidal effects on AromP450 in adult orchiectomized and adrenalectomized (OCX + ADX) male rats. As a result, prominent mRNA signals were detected in the fetal (i.e., the anterior medial preoptic nucleus) and fetoneonatal (i.e., the medial preopticoamygdaloid neuronal arc) groups, although no detectable signal was found in the "young-to-adult" group (i.e., the central amygdaloid nucleus). In addition, the "fetoneonatal" AromP450-I neurons were prominently reduced in number and intensity after OCX + ADX and then were reinstated by the administration of dihydrotestosterone, testosterone, or 17beta-estradiol. In contrast, none of the sex steroids had any significant effects on the young-to-adult group. Several possible explanations were explored for why the young-to-adult group may differ in aromatase expression and regulation, including the possibility that distinct splicing variants or isozymes for aromatase exist in the rat brain.