Increased activation of nuclear factor kappaB triggers inflammation and insulin resistance in polycystic ovary syndrome.
BACKGROUND
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 nuclear factor kappaB (NFkappaB) activation and inhibitory kappaB (IkappaB) from mononuclear cells (MNC) in PCOS.


METHODS
This was a prospective controlled study conducted at an academic medical center.


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


METHODS
Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (IS(OGTT)). Intranuclear NFkappaB and IkappaB protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion.


RESULTS
IS(OGTT) was lower in PCOS compared with controls (3.3 +/- 0.3 vs. 6.4 +/- 0.9, P < 0.004). The percent change in intranuclear NFkappaB was higher in lean and obese PCOS compared with lean controls (42.5 +/- 19.1 and 54.5 +/- 12.5 vs. -14.1 +/- 10.9, P < 0.006). The percent change in intranuclear NFkappaB correlated positively with 2-h post-glucose ingestion levels (r = 0.37; P < 0.04) and plasma testosterone (r = 0.49; P < 0.006) and correlated negatively with IS(OGTT) (r = 0.39; P < 0.04). The percent change in IkappaB was lower in lean and obese PCOS compared with lean controls (-22.3 +/- 3.2 and -17.0 +/- 5.0 vs. 8.4 +/- 11.8, P < 0.02).


CONCLUSIONS
In response to hyperglycemia, intranuclear NFkappaB increases and IkappaB decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.
González
Frank
F
Department of Obstetrics and Gynecology, MetroHealth Medical Center, Hamann S4-44, 2500 MetroHealth Drive, Cleveland, OH 44109, USA. fgonzalez@metrohealth.org
Rote
Neal S
NS
Minium
Judi
J
Kirwan
John P
JP
D000328:Adult; D000735:Androstenedione / Q000097:blood; D001711:Biotransformation; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D020672:I-kappa B Proteins / Q000096:biosynthesis; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D007333:Insulin Resistance / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D016759:Oncogene Protein p65(gag-jun) / Q000096:biosynthesis; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D011446:Prospective Studies; D013739:Testosterone / Q000097:blood; D049629:Waist-Hip Ratio
D001786:Blood Glucose; D020672:I-kappa B Proteins; D016328:NF-kappa B; D016759:Oncogene Protein p65(gag-jun); D013739:Testosterone; D000735:Androstenedione; D005947:Glucose