Insulin resistance directly contributes to androgenic potential within ovarian theca cells.
Fertil Steril. 2009 May;91(5 Suppl):1990-7. Epub 2008 Jul 30. PMID: 18672234
OBJECTIVE: To investigate whether insulin resistance (IR) within theca cells may directly contribute to their hyperandrogenism, a heritable trait of polycystic ovary syndrome (PCOS). DESIGN: In vitro cell model. SETTING: University-affiliated laboratory. ANIMAL(S): Porcine ovaries. INTERVENTION(S): Ovarian theca cells from porcine follicles were isolated and cultured. Insulin resistance was induced in theca cells without (Con) or with dexamethasone (Dex); cells were further treated by troglitazone (Tro) and metformin (Met) in IR cells or by vehicle only in IR and Con cells. MAIN OUTCOME MEASURE(S): Medium glucose and T levels; reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot for insulin signal molecules and androgenic enzyme. RESULT(S): As compared with Con cells, Dex-treated cells had significantly lower [(3)H]-glucose uptake (565 +/- 58 cpm/10(6) vs. 1077 +/- 78 cpm/10(6)) but higher medium glucose levels (16.31 +/- 0.39 nmol/L vs. 10.62 +/- 1.02 nmol/L) and had approximately twofold T levels (0.82 +/- 0.20 microg/L vs. 0.38+/-0.08 microg/L). Troglitazone and Met significantly reduced the medium glucose and testosterone concentrations to levels comparable to those in Con cells. The RT-PCR and Western blot showed that the two sensitizers in different ways reversed the altered messenger RNA and protein expression of insulin receptor substrate-1, glucose transporter-4, peroxisome proliferator-activated receptor-gamma, and 17 alpha-hydroxylase in Dex-induced IR cells. CONCLUSION(S): Insulin resistance induced by Dex could directly exaggerate androgenic potential within theca cells, suggesting the possible involvement of this ovarian metabolic phenotype in PCOS hyperandrogenism.