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J Clin Endocrinol Metab. 2006 Jan;91(1):336-40. Epub 2005 Oct 25.

Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome.

Author information

1
Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, USA. fgonzalez@metrohealth.org

Abstract

CONTEXT:

Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome (PCOS).

OBJECTIVE:

The purpose of this study was to determine the effects of hyperglycemia on reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS.

DESIGN:

This was a prospective controlled study.

SETTING:

The study was conducted at an academic medical center.

PATIENTS:

The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese).

MAIN OUTCOME MEASURES:

Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (IS(OGTT)). ROS generation and p47(phox) protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion.

RESULTS:

IS(OGTT) was lower in PCOS, compared with controls (3.1 +/- 0.3 vs. 6.3 +/- 0.9, P < 0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 +/- 21.3 and 154.2 +/- 49.1 vs. 0.6 +/- 12.7, P < 0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P < 0.05), and plasma levels of testosterone (r = 0.59, P < 0.002) and androstenedione (r = 0.50, P < 0.009). The percent change in p47(phox) from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 +/- 18.2 and 39.1 +/- 8.0 vs. -13.7 +/- 8.7, P < 0.02), and correlated negatively with IS(OGTT) (r = -0.39, P < 0.05).

CONCLUSION:

ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.

PMID:
16249279
DOI:
10.1210/jc.2005-1696
[Indexed for MEDLINE]
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