Hypothalamic aromatase cytochrome P450 and 5α-reductase enzyme activities in pregnant and female rats

The metabolism of steroid hormones in the medial basal hypothalamus (MBH) is known to play a critical role in neural development, the modulation of neuroendocrine function and regulating sexual behavior. While the important biological functions of the aromatase enzyme are well established, the importance of brain 5α-reductase has been revealed and elucidated only in the last few years. The distribution and regulation of brain aromatase and 5α-reductase enzyme activities have been investigated for the most part in male rats. Therefore, in the present study, MBH aromatase cytochrome P450 and 5α-reductase activities were characterized in pregnant and female rats during postnatal development under various hormonal conditions. MBH aromatase activity was determined in each tissue sample using the ‘tritiated water release’ assay, whereas, the 5α-reductase rates were determined by thin layer chromatography and scintillation counting of the isolated 5α-metabolites. Both activities were highest in infantile animals, then declined with increasing postnatal age; whereas, in aged non-cycling or ovariectomized/adrenalectomized (Ovx/Adx) rats high rates of androgen metabolism were seen in MBH tissue. No significant alterations in MBH aromatase were observed when the 5α-reductase pathway was blocked in pregnant animals during late gestation with a known 5α-reductase inhibitor (Proscar). However, plasma estradiol levels were significantly increased in the Proscar-treated animals. These results indicate that: 1) the decreasing MBH aromatase and 5α-reductase profile (in infantile to adult cycling animals) is developmentally regulated, 2) evidently, there is a divergent regulatory mechanism controlling MBH aromatase versus 5α-reductase in aged animals where the aromatase activity increased in aged non-cycling and Ovx/Adx rats while 5α-reductase rates remained at moderate levels and, 3) apparently, the 5α-reductase pathway is not involved in regulating MBH aromatase activity during late pregnancy.