The ovary and follicle development
Insulin Resistance Directly Contributes to Androgenic Potential Within Ovarian Theca Cells

https://doi.org/10.1016/j.fertnstert.2008.02.167Get rights and content
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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 [3H]-glucose uptake (565 ± 58 cpm/106 vs. 1077 ± 78 cpm/106) 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 μg/L vs. 0.38±0.08μg/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-γ, and 17α-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.

Key Words

Insulin resistance
ovarian theca cells
insulin sensitizers
PCOS

Cited by (0)

J.W.Q. has nothing to disclose. Y.W. has nothing to disclose. X.W. has nothing to disclose. L.G. has nothing to disclose. L.H. has nothing to disclose. R.E. has nothing to disclose.

Supported by the Nature Science Foundation of China (30572404), the Nature Science Foundation of Heilongjiang Province (ZJY0506-01), the Heilongjiang Oversea Scholars Project (1151HZ010), Heilongjiang Postdoctoral Financial Assistance (LBH-Z05230), and the Sino-Finish Scientific and Technological Cooperation (11th session for 2004–2006).

Presented in abstract form at the 62nd Annual Meeting of the American Society for Reproductive Medicine, October 21–25, 2006, New Orleans, Louisiana.

J.W. Qu and Y. Wang contributed equally to this work and served as co-authors.