Transient Sex Differences of Aromatase (CYP19) mRNA Expression in the Developing Rat Brain

Abstract

Sex differences in the activity of aromatase cytochrome P450 (CYP19) in the rat brain have been reported during pre- and postnatal development. It is unclear, however, whether these differences are reflected by corresponding differences in specific mRNA levels. To address this question, we have examined aromatase mRNA levels in specific regions of male and female rat brains by means of in situ hybridization (ISH). At prenatal stages of development, i.e. at gestational day 18 (GDI8) and GD20, aromatase mRNA was detected in several preoptic, hypothalamic and limbic brain regions. Semiquantitative analysis of aromatase mRNA did not reveal sex differences in any of these regions. In contrast, clear-cut sex differences were determined at postnatal day (PN) 2; male animals expressed significantly more aromatase mRNA in the bed nucleus of stria terminalis (BST) and the sexually dimorphic nucleus of the preoptic area (SDN). Smaller but still significant differences (females > males) were obtained in the medial preoptic area (MPO). At PN6, sex differences of aromatase mRNA signals (males > females) were still present in the BST, but were no longer detectable in the SDN and the MPO. At PN15 and in adult animals, aromatase mRNA levels were similar in BST and medical amygdaloid nucleus of male and female rats. Since aromatase mRNA expression decreases during postnatal development, no ISH signals could be detected anymore in MPO, SDN and ventromedial hypothalamic nucleus. Our results are consistent with the concept that differential regulation of aromatase mRNA expression might be important for the establishment of different neuronal circuitry in male and female animals.

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

“…6). In agreement with this observation, no previous radioisotopic ISH, which is more sensitive than the current ISH with the DIG-labeled cRNA probes, has ever explicitly demonstrated significant hybridization signals of AromP450 mRNA in the "young-to-adult group" (Lauber and Lichtensteiger, 1994;Lauber et al, 1997;Roselli et al, 1998). Although one study described diffusely disseminated weak signals in wide ranges of the rat forebrain, including the lCeAm, ovBST, and LS (Wagner and Morrell, 1996), the weak autoradiographic signals are difficult to interpret and might have been due to just the minor cross-hybridization signals with other mRNAs resembling part of AromP450 sequence or nonspecific background signals as often seen in the radioisotope-labeled ISH.…”

“…Although such a discrepancy is considered to be attributable to different recognition sites or cross-reactions among those antisera (see Shinoda, 1994a), the current IHC and ISH histochemical results in serial sections have definitively shown that the major aromatizing neurons are localized to the mPOAM in terms of their prominent immunoreactivity, hybridization signals, and cell numbers. Previous radioisotope-labeled ISH studies (although they might be less appropriate for detailed histochemical analyses than nonradioisotopelabeled ISH ones) have also shown the localization of the major AromP450 mRNA expression in the mPOAM of mammalian brains (Lauber and Lichtensteiger, 1994;Morell, 1996, 1997;Lauber et al, 1997;Roselli et al, 1998Roselli et al, , 2001). The results of those reports with different kinds of oligo-DNA or cRNA probes (Table 3) still basically correlated with those of our present study.…”

Sex chromosome complement determines sex differences in aromatase expression and regulation in the stria terminalis and anterior amygdala of the developing mouse brain

“…During brain differentiation aromatase mRNA in the hypothalamus increases gradually to reach peaks shortly before and after birth in rats Lephart et al, 1992) and mice (Harada and Yamada, 1992). In the bed nucleus of the stria terminalis and the sexually dimorphic nucleus of the preoptic area some sex differences were found with a higher expression of aromatase mRNA in male rats at P2; and later in development, at P6, the sex differences only remained in the bed nucleus of the stria terminalis (Lauber et al, 1997). Some of the sex differences in aromatase expression could not be explained by organizational actions of gonadal hormones.…”

“…The expression pattern of aromatase is restricted to discrete regions of the central nervous system, according to in situ hybridization and immunohistochemical studies (Lauber et al, 1997;Shinoda et al, 1994;Tsuruo et al, 1994). Several studies demonstrated that during the critical period of sexual differentiation there are sex differences in aromatase expression that are time-and regionally specific (Lauber et al, 1997). Most of the studies focused on the expression in sexually dimorphic brain areas, such as the hypothalamus and the preoptic area.…”

Distribution and sex differences in aromatase-producing neurons in the brain of Japanese quail embryos

“…In developing rodents, analysis of ARO mRNA expression and of ARO-immunoreactivity did not reveal sex differences during the fetal stage (Tsuruo et al, 1994;Lauber et al, 1997). However, an overall male-biased higher AROimmunoreactivity (Tsuruo et al, 1994) and a transient sex difference in ARO-mRNA expression in the bed nucleus of the stria terminalis and in the preoptic area of rats (Lauber et al, 1997) characterized the first two weeks of life. Among birds, developing Fig.…”