Aromatase Activity in Adult Guinea Pig Brain is Androgen Dependent1

Abstract

Androgen metabolism in target tissues constitutes an important step for understanding hormone action. The in situ aromatization of androgen represents one of these metabolic events. We characterized aromatase activity (AA) in a microsomal preparation of brain tissue from adult guinea pigs since earlier reports questioned its presence in neural tissues of this species. Analyses revealed an apparent substrate affinity (approximately 17 nM) that was equivalent in adult males and females. However, adult male brains contained greater quantities of AA than female brains. Specifically, AA in the preoptic area (POA: p less than 0.05) and the medial basal hypothalamus (MBH; p less than 0.01) was greater in males than in females. AA was concentrated in the limbic system and hypothalamus (amygdala greater than POA greater than septum greater than MBH), whereas low levels were consistently measured in cortical tissue. In vitro estrogen formation was significantly lower in POA (p less than 0.05) and MBH (p less than 0.01) after castration. After dihydrotestosterone treatment, AA returned to levels equal to or greater than those observed in intact males. These data indicate that AA does exist in the guinea pig brain and is modulated by androgens through the androgen receptor. The presence of high levels of aromatase activity may suggest a role for locally formed estrogens in brain function in this species.

Synergistic Induction of Aromatase Activity in the Rat Brain by Estradiol and 5α-Dihydrotestosterone

“…Both testosterone and DHT stimulate estrogen formation in castrated rats, and llutamide, a nonsteroidal antiandrogen, inhibits AA induction by testosterone [12]. More recently, we demonstrated that DHT stimulates the in vitro formation of estrogens in guinea pig brains as well [29]. In contrast to these results, DHT does not affect brain AA in doves and goldfish [16,18].…”

“…AA in the medial and cortical amygdala is independent of androgen, whereas AA throughout the hypo thalamus and POA is induced by testosterone acting through the androgen receptor. In addition, it has been demonstrated in other species that the response of AA to castration, testosterone stimulation and various environmental stimuli is regionally spe cific [3,15,16,18,29,[40][41][42][43][44]. Taken together these data suggest that there are likely to be cell populations which contain aroma tase which is regulated by androgen, estrogen or a combination of both steroids and other cells containing aromatase which is independent of steroid control.…”

Sex Differences in Androgen Responsiveness in the Rat Brain: Regional Differences in the Induction of Aromatase Activity

“…These results suggest that both the regional differences and sex differences in the basal capac ity of the brain to synthesize estrogens are due to differ ences in enzyme concentrations rather than to the exis tence of catalytically distinct forms of aromatase or mod ulation by competitive/uncompetitive inhibitors. Pheno typic sex differences in aromatase activity have been observed in several other vertebrate species [12,13,[23][24][25], Recent immunocytochemical studies found that in the medial preoptic region males have a greater density of aromatase-positive cells than females [25,26], which could account for the sex difference measured in enzyme activity.…”

Some rewarding effects of androgens may be mediated by actions of its 5α-reduced metabolite 3α-androstanediol

“…Indeed, in situ aromatization of androgens represents is an important metabolic event. Connolly, Roselli, and Resko (1990) have demonstrated that adult male guinea pig brains contained higher quantities of androgen aromatase than female brains. Androgen aromatase is concentrated in the limbic system and hypothalamus (amygdala, preoptic area, septum, hippocampus, and medial basal hypothalamus), whereas low levels were consistently found in cortical tissue (McEwen, 1980).…”