Increased aromatase activity in pubic skin fibroblasts from patients with isolated gynecomastia

Aromatase activity (AR) was studied in pubic skin fibroblasts from eight patients with isolated gynecomastia (PSFG) and five normal subjects (PSFC). Cell monolayers were incubated in the presence of [3H]androstenedione (2 nM) for 4 or 24 h. Culture medium was extracted after addition of [14C] carriers to monitor recovery. Metabolites were separated by two successive chromatographic steps. Estrone (E1) and estradiol (E2) were characterized by crystallization, the other metabolites: 16-hydroxyestrone (16 alpha-OHE1) estriol (E3), and epiestriol (epiE3) by their chromatographic migration. AR was expressed either as femtomoles of E2 per microgram DNA (ARE2) or as total aromatized metabolites (ART = E1 + E2 + 16 alpha-OHE1 + E3 + epiE3/microgram DNA). After 4 h of incubation, no ARE2 could be measured in PSFC; it was low but significant in PSFG (0.03 +/- 0.02 (SEM) fmol/microgram DNA, P less than 0.01). The difference in ART was even more striking: 0.28 +/- 0.1 fmol/microgram DNA in PSFC, 3.15 +/- 2.88 in PSFG (P less than 0.05). 16 alpha-OHE1 represented in this latter group 62.5% of total aromatized metabolites vs. 39% in PSFC. After 24 h, ART was 4.17 +/- 3.70 and 1.02 +/- 0.42 fmol/microgram DNA in PSFG and PSFC, respectively (P less than 0.05); E3 + epiE3 represented 50% of the metabolites in both groups. In conclusion, AR is increased in PSFG relative to PSFC and an important oxidative metabolism of estrogens exists in both types of cells. This increased peripheral AR could result in increased formation of estrogens at the target cell site and represent an element of androgen-estrogen imbalance which would favor the development of gynecomastia.