Insulin resistance directly contributes to androgenic potential within ovarian theca cells.
OBJECTIVE
To investigate whether insulin resistance (IR) within theca cells may directly contribute to their hyperandrogenism, a heritable trait of polycystic ovary syndrome (PCOS).


METHODS
In vitro cell model.


METHODS
University-affiliated laboratory.


METHODS
Porcine ovaries.


METHODS
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.


METHODS
Medium glucose and T levels; reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot for insulin signal molecules and androgenic enzyme.


RESULTS
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.


CONCLUSIONS
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.
Qu
JunWei
J
Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
Wang
Yong
Y
Wu
Xiaoke
X
Gao
Lei
L
Hou
Lihui
L
Erkkola
Risto
R
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002839:Chromans / Q000494:pharmacology*; D005260:Female; D051275:Glucose Transporter Type 4 / Q000187:drug effects / Q000235:genetics*; D055504:Insulin Receptor Substrate Proteins / Q000187:drug effects / Q000235:genetics; D007333:Insulin Resistance / Q000502:physiology*; D008687:Metformin / Q000494:pharmacology*; D047495:PPAR gamma / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000187:drug effects / Q000235:genetics; D013552:Swine; D013799:Theca Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D000728:Androgens; D002839:Chromans; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D008687:Metformin; D013254:Steroid 17-alpha-Hydroxylase; D000077288:Troglitazone