PMID- 14556818
OWN - NLM
STAT- MEDLINE
DCOM- 20031124
LR  - 20190707
IS  - 0015-0282 (Print)
IS  - 0015-0282 (Linking)
VI  - 80
IP  - 4
DP  - 2003 Oct
TI  - Selective ovary resistance to insulin signaling in women with polycystic ovary 
      syndrome.
PG  - 954-65
AB  - OBJECTIVE: Insulin resistance is a common feature of both polycystic ovary 
      syndrome (PCOS) and non-insulin-dependent diabetes mellitus (NIDDM); however, the 
      persistent reproductive disturbances appear to be limited to the former, 
      suggesting that insulin resistance in the ovary itself may confer this 
      susceptibility. DESIGN: Prospective study. SETTING: University-affiliated 
      department. PATIENT(S): Forty-four women undergoing IVF treatment, of whom 11 had 
      polycystic ovaries and 33 had normal ovulation (NO). INTERVENTION(S): The various 
      effects and signaling of insulin and insulin-like growth factor-1 (IGF-1) were 
      examined in cultured ovarian granulosa cells treated with troglitazone (1 
      microg/mL) or with vehicle by reverse transcription-polymerase chain reaction, 
      western blot, and in vitro functional analyses. MAIN OUTCOME MEASURE(S): Glycogen 
      and DNA syntheses, mRNA and protein expression, and cellular localization of 
      insulin/IGF-1 receptors and insulin receptor substrates (IRSs). RESULT(S): There 
      were significant decreases in insulin-stimulated glucose incorporation into 
      glycogen in PCOS cells, which is a metabolic action of insulin. However, IGF-1 
      stimulation was found to be greater in PCOS cells at all experimental 
      concentrations with respect to thymidine incorporation compared with NO cells, 
      which is a mitogenic action. Troglitazone increased the insulin-induced glycogen 
      synthesis but reduced the IGF-1-augmented responses of DNA synthesis in PCOS 
      cells to the range within those of NO granulosa cells. We then found that 
      troglitazone treatment reversed the expression imbalance between IRS-1 and IRS-2 
      in PCOS cells. CONCLUSION(S): There is a selective defect in insulin actions in 
      PCOS granulosa cells, which suggests ovarian insulin resistance, and this 
      metabolic phenotype is associated with an enhanced IGF-1 mitogenic potential. 
      Troglitazone could divergently alter expression of various IRS molecules and 
      insulin actions and could be used as an ovarian insulin sensitizer and 
      mitogen/steroidogenic inhibitor in PCOS.
FAU - Wu, Xiao Ke
AU  - Wu XK
AD  - Department of Obstetrics and Gynecology, School of Clinical Medicine, Jinling 
      Hospital of Nanjing University, Nanjing, China. xiaokewu2002@sina.com
FAU - Zhou, Shan Ying
AU  - Zhou SY
FAU - Liu, Jin Xia
AU  - Liu JX
FAU - Pollanen, Pasi
AU  - Pollanen P
FAU - Sallinen, Kirsimarja
AU  - Sallinen K
FAU - Makinen, Marjaana
AU  - Makinen M
FAU - Erkkola, Risto
AU  - Erkkola R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Fertil Steril
JT  - Fertility and sterility
JID - 0372772
RN  - 0 (Chromans)
RN  - 0 (IRS1 protein, human)
RN  - 0 (IRS2 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thiazolidinediones)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - I66ZZ0ZN0E (Troglitazone)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adult
MH  - Cells, Cultured
MH  - Chromans/pharmacology
MH  - DNA/biosynthesis
MH  - Female
MH  - Glucose/metabolism
MH  - Granulosa Cells/metabolism
MH  - Humans
MH  - Insulin/*metabolism/pharmacology
MH  - Insulin Receptor Substrate Proteins
MH  - *Insulin Resistance
MH  - Insulin-Like Growth Factor I/metabolism/pharmacology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Ovary/metabolism/pathology/*physiopathology
MH  - Phosphoproteins/genetics
MH  - Polycystic Ovary Syndrome/metabolism/pathology/*physiopathology
MH  - Prospective Studies
MH  - RNA, Messenger/metabolism
MH  - Receptor, IGF Type 1/genetics
MH  - Receptor, Insulin/genetics
MH  - *Signal Transduction
MH  - Thiazolidinediones/pharmacology
MH  - Troglitazone
EDAT- 2003/10/15 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/10/15 05:00
PHST- 2003/10/15 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/10/15 05:00 [entrez]
AID - S0015028203010070 [pii]
AID - 10.1016/s0015-0282(03)01007-0 [doi]
PST - ppublish
SO  - Fertil Steril. 2003 Oct;80(4):954-65. doi: 10.1016/s0015-0282(03)01007-0.