G R Attia1, W E Rainey, B R Carr. 1. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9032, USA.
Abstract
OBJECTIVE: To examine the direct effect of metformin on thecal cell androgen production. SETTING: 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.
OBJECTIVE: To examine the direct effect of metformin on thecal cell androgen production. SETTING: 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.
Authors: Leopoldo O Tso; Michael F Costello; Luiz Eduardo T Albuquerque; Régis B Andriolo; Cristiane R Macedo Journal: Cochrane Database Syst Rev Date: 2014-11-18