REGULATION SYSTEM AND PHYSIOLOGICAL SIGNIFICANCE OF AROMATASE ACTIVITY ON HYPOTHALAMUS-PREOPTIC AREA IN THE RAT

Sexual differentiation of brain structure and function is dependent on the hormone environment during perinatal life. Especially, estrogen has been implicated in the process of masculinization of brain. Aromatase, converted androgen to estrogen, in the brain was reported that it was associated with sexual differentiation and sexual behavior, and regulated by androgen. However, the regulation system and physiological significance of aromatase in the brain remains obscure. In this present study, it has examined that distribution and change with age of aromatase activities in the brain, and effects of androgen, antiandrogen, progesterone and hypophysectomy on aromatase activity of hypothalamus-preoptic area (HPOA), and effects of aromatase inhibitor on sexual behavior.The greatest amount of aromatase activity have found in HPOA and amygdala, associated with sexual differentiation and sexual behavior, but cerebral cortex, cerebellum, pituitary and thalamus all contained negligible aromatase activity. HPOA aromatase activity increased at perinatal period, which was critical period of sexual differentiation in the brain, and declined to 3 weeks after birth. HPOA aromatase activity was increased by androgen, progesterone and progesterone derivatives, and decreased by castration, non-steroidal antiandrogens and drugs decreased serum testosterone concentration. Moreover, it found that there was no relation between the hypophysis and regulation of HPOA aromatase activity.Pregnant female rats were given daily injections of aromatase inhibitor, throughout the latter half of the pregnancy. Significant reductions were detected in HPOA aromatase activity of the male fetuses and pups. Behavioral consequences of the prenatal treatment were examined in adulthood. Partial but significant protection of the behavioral defeminization was associated with the decreased HPOA aromatase activity during the prenatal period. However, aromatase inhibitor treatment as adult male rats failed to produce any detectable change in sexual behavior.These results suggested that aromatase in the brain played an important role in the sexual differentiation of the brain for defeminization at the critical period. And, it was regulated by androgen and progestin independently of the hypophyseal system.