Neurosteroids and libido
Neurosteroids and the proteins responsible for their synthesis from cholesterol are found
in structures critical for sexual desire in males and females, such as the amygdala, medial
preoptic area (MPOA), and ventral medial hypothalamus (VMH). These areas are rich in receptors affected by neurosteroids. Neurosteroids elicit different responses in males and females. Animal studies link neurosteroids to the regulation of the hypothalamic- pituitary-gonadal axis, including both enhancement and suppression of sexual motivation and behavior. For instance, activation of hypothalamic GABA-A receptors by allopregnanolone, a neuroactive metabolite of progesterone, in female rats can lead to suppression of ovulation and can have either positive or negative effects on sexual behavior. The inhibition of gonadotropin-releasing hormone (GnRH) in the hypothalamus by allopregnanolone release can be antagonized by pregnenolone sulfate. In addition, 3á-androstanediol attenuates lordosis and promotes aggression in female rats, probably through GABA-A receptor inhibition in the medial basal hypothalamus and MPOA. Moreover, problems that interfere with sexual behavior and function such as depression and premenstrual syndrome correlate with changes in serum neurosteroid levels in humans. In male mice, a commonly used performance test for sexual behavior involving preference for the odors of estrous females was enhanced by intra-cerebroventricular administration of the progesterone metabolite 3á- hydroxy-4-pregnen-20-one and reduced by pregnenolone sulfate. Because androgens and progesterone are synthesized in the brain, some of the effects of these steroids on sexual behavior may be mediated in part by their local synthesis. For instance, administration of estradiol rapidly induces copulatory behavior in male rats. Although estrogen derived from the aromatization of gonadal testosterone is critical to maintain sensitivity for sexual stimulation in the male, these and later studies suggest that copulatory behavior can be triggered by estrogen produced de novo in the brain itself.