Molecular Human Reproduction, Vol. 8, No. 5, 456-464,
May 2002
© 2002 European Society of Human Reproduction and Embryology
Uterine physiology |
Increased leptin expression in endometriosis cells is associated with endometrial stromal cell proliferation and leptin gene up-regulation
1 Institute of Clinical Medicine and Department of Obstetrics and Gynecology and 2 Department of Physiology, College of Medicine, National Cheng-Kung University, Tainan 70101, Taiwan, R.O.C.
Endometriosis is a polygenic disease with complex, multifactorial aetiologies affecting ~10% of women of reproductive age. Leptin is the product of the ob gene, which is related to reproductive function and immunological alteration. The angiogenic and mitogenic action of leptin may influence the formation of endometriosis. This study was aimed at determining whether leptin and leptin receptor expression differs in eutopic and ectopic endometria collected from laparoscopy and at investigating the pathophysiological role of leptin in the development of endometriosis. Leptin mRNA was undetectable in seven out of 14 eutopic endometria and only a minute amount was detected in the remaining samples. In contrast, there was a marked increase in leptin mRNA and protein expression in ectopic endometriotic lesions of patients with endometriosis (P < 0.05). Receptors for leptin were immunologically stained in eutopic endometrium as well as in ectopic endometriotic implants. However, the levels of mRNA for the long and total forms of leptin receptors were suppressed in association with the severity of endometriosis (P < 0.05). Administration of leptin stimulated its own mRNA expression in ectopic endometriotic stromal cells but decreased steady-state concentrations of mRNA encoding for leptin receptor (n = 6). In addition, leptin significantly enhanced both eutopic and ectopic endometrial stromal cell proliferation (P < 0.05). In conclusion, the differential distribution of mRNA for leptin and its receptor suggests an important autocrine and paracrine role for leptin in human endometriosis. The mitogenic and auto-augmentation effects of leptin may further contribute to the pathogenesis of endometriosis.
endometriosis/leptin/leptin receptor/quantitative RT PCR/[3H]thymidine incorporation
3 To whom correspondence should be addressed. E-mail: seantsai{at}mail.ncku.edu.tw
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