TY - JOUR
T1 - Sex differences in androgen-regulated expression of cytochrome P450 aromatase in the rat brain
AU - Roselli, Charles E.
AU - Resko, John A.
N1 - Funding Information:
Acknowledgements--Portions of this work were supported by NSF gram IBN 94-21759 (C.E.R.) and NIH grants HD-18196 (C.E.R.), HD-23293 (J.A.R.) and P30-HD-18185.
PY - 1997/4
Y1 - 1997/4
N2 - The basis of functional gender differences in adult responsiveness to testosterone (T) is not yet understood. Conversion of T to estradiol by cytochrome P450 aromatase in the medial preoptic area is required for the full expression of male sexual behavior in rats. High levels of aromatase are found in the medial preoptic nucleus (MPN) and in an interconnected group of sexually dimorphic nuclei which mediate masculine sexual behavior. Within this neural circuit, aromatase is regulated by T, acting through an androgen receptor (AR)-mediated mechanism. This arrangement constitu- tes a feedforward system because T is both the regulator and the major substrate of aromatase. Pre- optic aromatase is thus more active in adult males than in females because of normal sex differences in circulating androgen levels. However, the mechanism of enzyme induction also appears to be sexually dimorphic because equivalent physiological doses of T stimulate aromatase to a greater extent in males than in females. Dose-response studies indicate that the sex difference is apparent over a range of circulating T concentrations and constitute a gender difference in T effi- cacy, but not potency. Sex differences in aromatase correlate with sex differences in nuclear AR concentrations in most regions of the sexually dimorphic neural circuit, but not in MPN. These results suggest that males may have larger populations of target cells in which aromatase is regu- lated by androgen, but the lack of a gender difference in AR levels in the MPN suggests that differ- ences in post-receptor mechanisms could also be involved. Measurements of aromatase mRNA in androgen-treated gonadectomized rats demonstrate that sex difference in regulation is exerted pre- translationally. Taken together these results demonstrate a sexually dimorphic mechanism that could potentially limit the action of T in females, and may relate to the enhanced expression of T- stimulated sexual behaviors in males.
AB - The basis of functional gender differences in adult responsiveness to testosterone (T) is not yet understood. Conversion of T to estradiol by cytochrome P450 aromatase in the medial preoptic area is required for the full expression of male sexual behavior in rats. High levels of aromatase are found in the medial preoptic nucleus (MPN) and in an interconnected group of sexually dimorphic nuclei which mediate masculine sexual behavior. Within this neural circuit, aromatase is regulated by T, acting through an androgen receptor (AR)-mediated mechanism. This arrangement constitu- tes a feedforward system because T is both the regulator and the major substrate of aromatase. Pre- optic aromatase is thus more active in adult males than in females because of normal sex differences in circulating androgen levels. However, the mechanism of enzyme induction also appears to be sexually dimorphic because equivalent physiological doses of T stimulate aromatase to a greater extent in males than in females. Dose-response studies indicate that the sex difference is apparent over a range of circulating T concentrations and constitute a gender difference in T effi- cacy, but not potency. Sex differences in aromatase correlate with sex differences in nuclear AR concentrations in most regions of the sexually dimorphic neural circuit, but not in MPN. These results suggest that males may have larger populations of target cells in which aromatase is regu- lated by androgen, but the lack of a gender difference in AR levels in the MPN suggests that differ- ences in post-receptor mechanisms could also be involved. Measurements of aromatase mRNA in androgen-treated gonadectomized rats demonstrate that sex difference in regulation is exerted pre- translationally. Taken together these results demonstrate a sexually dimorphic mechanism that could potentially limit the action of T in females, and may relate to the enhanced expression of T- stimulated sexual behaviors in males.
UR - http://www.scopus.com/inward/record.url?scp=0031126716&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031126716&partnerID=8YFLogxK
U2 - 10.1016/S0960-0760(96)00232-4
DO - 10.1016/S0960-0760(96)00232-4
M3 - Article
C2 - 9365212
AN - SCOPUS:0031126716
SN - 0960-0760
VL - 61
SP - 365
EP - 374
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 3-6
ER -