ANDROSTENEDIONE

Androstenedione and testosterone labeled with 3H and 14C were fused simultaneously at constant rates into the brachial arm vein of 10 normal men. During the infusions blood samples were obtained from the brachial artery, a deep vein draining primarily muscle and a superficial vein draining primarily adipose tissue of the arm contra-lateral to the infusion. In the 10 men the mean +/- SE value for the fractional metabolism of adrostenedione by muscle is 0.20 +/- 0.30 which is not different from the mean value for the fractional metabolism by androstenedione by adipose tissue, 0.29 +/- 0.04. The mean value for the metabolism of testosterone by muscle, 0.04 +/- *.01, is significantly less than the metabolism by adipose tissue, *.11 +/- 0.01. Interconversion between adrostenedione and testosterone occurs in both tissues. The mean value for pA,T A,M is 0.024 + 0.005 and for pA,T A,AT is 0.024 +/- 0.005. The mean value for pT,A A,M is 0.005 +/- 0.003 and for pT,A A,AT is 0.008 +/- 0.003. The fractional metabolism of these androgens by these tissues is similar to the fractional metabolism of estrone and estradiol by these same tissues. Muscle appears to contribute about 5-12% of the overall metabolism of androstenedione and testosterone and 10-15% to theoverall conversion of androstenedione to testosterone. Adipose tissue contributes about 2-7% of the overall metabolism of these androgens and 5-10% of the overall conversion of androstenedione to testosterone, but less than 2% to the overall conversion of testosterone to androstenedione. In normal men, muscle appears to be more important to the metabolism of androstenedione and testosterone than is adipose tissue.

Longcope C, Pratt JH, Schneider SH, Fineberg SE. The in vivo metabolism of androgens by muscle andadiposetissue of normal men. Steroids 1976 Oct;28(4):521-533.

Bone is a target organ of androgens. The mechanism by which these steroids exert their action within bone cells is still poorly understood. The metabolism of androstenedione, the major circulating androgen in women, was, therefore, assessed in osteoblast-like bone cells cultured from bone of 16 postmenopausal women (mean age, 69 yr; range, 56-80) and 3 elderly men (mean age, 71 yr; range, 69-73) undergoing total hip replacement. Each cell strain was incubated under standardized conditions with varying concentrations of [1,2,6,7-3H]androstenedione (0.05-5 microM). In every instance 5 alpha-reduced metabolites and 17 beta-hydroxysteroids were formed. There was no correlation between the volumetric density of the resected bone and androstenedione metabolism of the corresponding cultured bone cell strains. The apparent Km for the 5 alpha-reductase activity (sum of androstanedione and dihydrotestosterone) of all 19 cell strains was 0.7 +/- 0.1 microM (mean +/- SEM), and the apparent Km for 17 beta-hydroxysteroid dehydrogenase (sum of testosterone and dihydrotestosterone) was 2.3 +/- 0.8 microM (mean +/- SEM), values similar to those reported for other androgen target organs. Our results demonstrate that human osteoblast-like cells have the capacity to transform androstenedione into the more potent biological androgens testosterone and dihydrotestosterone. Since the Km values of both 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase exceed the serum androstenedione concentration, the formation of testosterone and dihydrotestosterone appears to be mainly a function of substrate availability.

Bruch HR, Wolf L, Budde R, Romalo G, Schweikert HU. Androstenedione metabolism in cultured human osteoblast-like cells. J Clin Endocrinol Metab 1992 Jul;75(1):101-105.

The preceding abstracts were obtained from the MedLine service maintained by the National Institutes of Health.