Titre du document / Document title

Metformin directly inhibits androgen production in human thecal cells

Auteur(s) / Author(s)

ATTIA George R. ⁽¹⁾ ; RAINEY William E. ⁽¹⁾ ; CARR Bruce R. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, ETATS-UNIS

Résumé / 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, 17a-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 μM and 200 μM) 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 μM 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 17a-hydroxylase (CYP17) expression in cells stimulated with forskolin compared with forskolin treatment alone. There was no significant change in either 3β-hydroxysteroid dehydrogenase (3βHSD) 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 μM) 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.

Revue / Journal Title

Fertility and sterility   ISSN 0015-0282   CODEN FESTAS 

Source / Source

2001, vol. 76, n^o3, pp. 517-524 (49 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, New York, NY, ETATS-UNIS  (1950) (Revue)

Mots-clés anglais / English Keywords

Testicular hormone ; Androgen ; Sex steroid hormone ; Ovarian hormone ; Mechanism of action ; Female genital system ; Ovary ; Ovarian follicle ; Enzyme ; Oxidoreductases ; Human ; Female ; Hypoglycemic agent ; Hydroxylase ; Biguanides ; Metformin ; Gene expression ; Cytochrome P450 ; Androstenedione ; Testosterone ; Progesterone ; Steroidogenesis ; Theca folliculi ;

Mots-clés français / French Keywords

Hormone testiculaire ; Androgène ; Hormone stéroïde sexuelle ; Hormone ovarienne ; Mécanisme action ; Appareil génital femelle ; Ovaire ; Follicule ovarien ; Enzyme ; Oxidoreductases ; Homme ; Femelle ; Hypoglycémiant ; Hydroxylase ; Biguanides ; Metformine ; Expression génique ; Cytochrome P450 ; Androstènedione ; Testostérone ; Progestérone ; Stéroïdogenèse ; Thèque folliculaire ;

Mots-clés espagnols / Spanish Keywords

Hormona testicular ; Andrógeno ; Hormona esteroide sexual ; Hormona ovárica ; Mecanismo acción ; Aparato genital hembra ; Ovario ; Folículo ovárico ; Enzima ; Oxidoreductases ; Hombre ; Hembra ; Hipoglicemiante ; Hydroxylase ; Biguanidas ; Metformina ; Expresión genética ; Citocromo P450 ; Androstenediona ; Testosterona ; Progesterona ; Esteroidogénesis ; Teca folicular ;

Localisation / Location

INIST-CNRS, Cote INIST : 4120, 35400009948804.0160