Influence of Adipose Tissue Distribution on the Biological Activity of Androgens^a

Abstract

To establish whether the conversion of androstenedione (A) to estrogens and 5 alpha-reduced metabolites in human adipose tissue was determined by the site of origin of the tissue, studies were carried out on adipose stromal cells from different body sites. Adipose tissue was obtained from the breast, omentum, abdomen, lower thigh, upper thigh, buttock, and flank from patients undergoing liposuction for cosmetic reasons or at surgery. Stromal cells were isolated after incubation of the adipose tissue with collagenase and were grown in culture using alpha-minimal essential medium (MEM) + 15% fetal calf serum. Studies of A metabolism were carried out when the cells were between days 4 and 12 in culture. After an 8-hour incubation with (3H)-A as substrate, estrone (E1), testosterone (T), 5 alpha-androstanedione (5 alpha-A-dione), androsterone (AND), and dihydrotestosterone (DHT) were isolated using thin layer and paper chromatography. The conversion per 1 x 10(6) cells of A of E1 was more than 10-fold greater in the upper thigh, buttock, and flank than in the breast, lower thigh, abdomen, or omentum (0.13-3.0 vs 0.01-0.09%). The formation of 5 alpha-reduced androgens varied from 0.86-10% and was similar in tissue from different body sites. Cortisol (10(-7) M) stimulated E1 formation 3- to 10-fold in cells from all sites, whereas 5 alpha-reductase activity was either unchanged or increased moderately (up to twofold). In cells from the abdomen, omentum, and lower thigh, the formation of 5 alpha-reduced androgens was more than 10-fold greater than the formation of E1. In cells from the upper thigh, buttock, and flank, E1 formation was comparable to 5 alpha-reduced androgen formation. These studies show marked differences in the relative conversion of A to estrogens and 5 alpha-reduced androgens in adipose stromal cells depending on their site of origin, and they suggest that the distribution of body fat may be a major factor in determining the biologic effects of secreted androgens.

The effect of obesity on the ratio of type 3 17β-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women

“…In cultured preadipocytes derived from human subcutaneous abdominal and omental adipose tissue, the formation of androgens from androstenedione was 10-fold greater than the formation of estrone, whereas in adipose tissue from the buttock and thigh, the production of androgens and estrone from androstenedione was equivalent. 7 Consistent with this, aromatase mRNA levels were higher in the buttocks than in subcutaneous abdominal adipose tissue of women. 8 These data suggest that there are regional variations in the level of expression of aromatase and 17b-HSD in the adipose tissue of women.…”

“…4,5 In adipose tissue, aromatase activity and mRNA is localised predominantly in preadipocytes. 5,6 Killinger et al 7 reported that there are regional differences in preadipocyte sex steroid production. In cultured preadipocytes derived from human subcutaneous abdominal and omental adipose tissue, the formation of androgens from androstenedione was 10-fold greater than the formation of estrone, whereas in adipose tissue from the buttock and thigh, the production of androgens and estrone from androstenedione was equivalent.…”

Androgen inactivation and steroid-converting enzyme expression in abdominal adipose tissue in men

“…25% estrone formation. The low rates of estrone formation in these cells (Killinger et al 1990) could not have been detected using our method. Altogether, our results do not seem to be in disagreement with other previous studies regarding aromatization in adipose tissue.…”

“…Thus, our finding of only moderate aromatase expression in such tissue samples is not surprising. Killinger et al (1990) also demonstrated that percent conversion of androstenedione to estrone ranged between 0 . 01 and 0 .…”

CYP19A1 genetic polymorphisms may be associated with obesity-related phenotypes in Chinese women

“…Aromatase activity is 6-30 times higher in fat taken from the upper thigh, buttocks and flank vs the abdomen. 24,25 It is also possible that aromatase regulation varies across fat deposit locations. 26 Thus, the effect of CYP19A1 polymorphisms on obesity-related phenotypes may differ across the body.…”