Results
| PMID | 15831279 |
| Gene Name | IL6 |
| Condition | Endometriosis |
| Association |
Associated |
| Sex | Female |
| Infertility type | Female infertility |
| Other associated phenotypes |
Endometriosis- related infertility |
|
Fertil Steril. 2005 Apr;83 Suppl 1:1086-92. Deura, Imari| Harada, Tasuku| Taniguchi, Fuminori| Iwabe, Tomio| Izawa, Masao| Terakawa, Naoki Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Mishimachi, Yonago 683-8504, Japan. imari@grape.med.tottori-u.ac.jp OBJECTIVE: To examine the effect of interleukin-6 (IL-6) on estrogen production and aromatase activity using a human granulosa tumor cell line (KGN cells). The involvement of the mitogen-activated protein kinase (MAPK) cascade in the inhibitory effects of IL-6 on estrogen production was also evaluated. DESIGN: Molecular and biological studies of KGN cells. SETTING: Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan. MAIN OUTCOME MEASURE(S): Gene expression of IL-6 and the IL-6 receptor was analyzed by reverse transcription-polymerase chain reaction and Southern blot analysis. KGN cells were cultured for 48 hours with IL-6 (0.1-10 ng/mL) or IL-6 (10 ng/mL) plus a mitogen activated protein kinase-extracellular signal regulated kinase kinase 1/2 (MEK1/2) inhibitor U0126 (10 microM). Estradiol concentration in the culture supernatants was measured by means of enzyme immunoassay, [1beta-(3)H] androstenedione was added to the cell lysate supernatant, and aromatase activity was determined by measuring the amount of [(3)H] H(2)O released upon the conversion of [1beta-(3)H] androstenedione to estrone. To examine the activation of intracellular signal transduction molecules induced by IL-6, the phosphorylation of Stat3, p38 MAPK, and extracellular signal-regulated kinase 1/2 (ERK1/2) was examined by Western blotting. RESULT(S): Gene expression of IL-6 and its receptor was detected in KGN cells. Estradiol secretion was significantly inhibited by adding IL-6, which also suppressed aromatase activity to 50% of the control. In addition, pretreatment with U0126 restored the IL-6-induced suppression of aromatase activity. IL-6 markedly enhanced the phosphorylation of ERK1/2, but not Stat3 and p38 MAPK. U0126 markedly reduced the level of the IL-6-induced phosphorylation of ERK1/2. CONCLUSION(S): These findings demonstrate that IL-6 may reduce estrogen production via the MAPK signal pathway in human granulosa cells. The results may support the notion that IL-6 is related to impaired estrogen biosynthesis in patients with endometriosis. Mesh Terms: Antigens, CD/genetics| Aromatase/metabolism| Cell Line, Tumor| Cytokine Receptor gp130| Endometriosis/metabolism/*physiopathology| Enzyme Activation/drug effects| Estradiol/*metabolism/secretion| Female| Humans| Infertility, Female/metabolism/*ph |
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