Fertility and Sterility, 76(3), 517-524, 2001
To examine the direct effect of metformin on thecal cell androgen production.
Basic science research laboratory, University of Texas Southwestern, Dallas, Texas.
INTERVENTION(S): Human ovarian theca-like tumor cells were treated with various concentrations of metformin in the presence and absence of forskolin for 48 hours.
MAIN OUTCOME MEASURE(S): Media were collected, and radioimmunoassay (RIA) for progesterone, 17 alpha-hydroxyprogesterone (17OHP), androstenedione, and testosterone was performed. The effect of metformin on the expression of various enzymes involved in theca cell steroidogenesis was examined.
RESULT(S): Metformin (50 microM and 200 microM) significantly inhibited androstenedione production from both forskolin-stimulated and unstimulated theca cells. Testosterone production was also significantly inhibited in forskolin-treated cells in the presence of 200 microM of metformin-treated compared with forskolin-only-treated cells. Western blot analysis revealed that metformin significantly inhibited the expression of steroidogenic acute regulatory (StAR) protein and 17 alpha-hydroxylase (CYP17) expression in cells stimulated with forskolin compared with forskolin treatment alone. There was no significant change in either 3beta-hydroxysteroid dehydrogenase (3 beta HSD) or cholesterol side-chain cleavage (CYP11A1) protein expression. Northern analysis revealed a significant decrease in the expression of CYP17 mRNA in forskolin-stimulated cells treated with metformin (200 microM) compared with forskolin-only-treated cells, however, there was no significant change in steroidogenic acute regulatory protein mRNA expression.
CONCLUSION(S): Our results suggest that metformin may have a direct effect on thecal cells' androgen production.
Attia, G. R., Rainey, W. E., & Carr, B. R. (2001). Metformin directly inhibits androgen production in human thecal cells. Fertility and sterility, 76(3), 517-524. https://doi.org/10.1016/s0015-0282(01)01975-6
Attia GR, Rainey WE, Carr BR. Metformin directly inhibits androgen production in human thecal cells. Fertil Steril. 2001;76(3):517-524. doi:10.1016/s0015-0282(01)01975-6
Attia, G. R., et al. "Metformin directly inhibits androgen production in human thecal cells." Fertility and sterility, vol. 76, no. 3, 2001, pp. 517-524.
17-alpha-Hydroxyprogesterone/metabolism, 3-Hydroxysteroid Dehydrogenases/genetics, Androgens/biosynthesis, Androstenedione/metabolism, Cells, Cultured, Cholesterol Side-Chain Cleavage Enzyme/genetics, Colforsin/pharmacology, Female, Gene Expression Regulation, Enzymologic/drug Effects, Humans, Metformin/pharmacology, Phosphoproteins/genetics, Progesterone/metabolism, RNA, Messenger/genetics, Steroid 17-alpha-Hydroxylase/genetics, Testosterone/metabolism, Theca Cells/cytology/drug Effects/metabolism, Transcription, Genetic/drug Effects, Androgens, Phosphoproteins, RNA, Messenger, Steroidogenic Acute Regulatory Protein, Colforsin, Testosterone, Androstenedione, Progesterone, 17-alpha-Hydroxyprogesterone, Metformin, 3-Hydroxysteroid Dehydrogenases, Steroid 17-alpha-Hydroxylase, Cholesterol Side-Chain Cleavage Enzyme