β-HCG/LH Receptor (β-HCG/LH-R) Expression in Eutopic Endometrium and Endometriotic Implants: Evidence for β-HCG Sensitivity of Endometriosis

Abstract

Background: Luteinizing hormone (LH) and human chorionic gonadotropin (HCG) target their receptor in gonadal and nongonadal cells to stimulate steroidogenesis and cell growth. The aim of the present study was to investigate the expression of HCG/LH-R in endometriosis to elucidate a possible impact of LH and HCG on this disease. Materials and methods: Analysis of HCG/LH-R protein expression in 23 paired samples of ectopic and eutopic tissue of cycling women with endometriosis and in endometrial samples from 22 healthy controls was conducted via immunofluorescence. HCG and HCG/LH-R gene expression in endometriotic lesions was confirmed by reverse-transcriptase polymerase chain reaction. Results: In endometriotic implants, epithelial HCG/LH-R was found in 12/23 samples. No significant differences in HCG/LH-R levels were observed when compared with glands of uterine endometrium from the same patients or healthy controls. Messenger RNA transcripts for HCG were detected in all 12 samples, whereas HCG/LH-R mRNAs were observed in 10 of the 12 endometriotic lesions investigated. Conclusions: Although HCG/LH-R was not found to be selectively upregulated in endometriosis, the mere presence of HCG/LH-R in endometriotic tissue may suggest sensitivity of endometriosis to HCG and LH that target HCG/LH-R.

Keywords

β-HCG-receptor endometriosis expression.

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References

Licht P. , Russu V. , Lehmeyer S. , Wildt L. Molecular aspects of direct LH/hCG effects on human endometrium-lessons from intrauterine microdialysis in the human female in vivo. Reprod Biol. 2001;1:10-19.

Licht P. , von Wolff M. , Berkholz A. , Wildt L. Evidence for cycle-dependent expression of full-length human chorionic gonadotropin/luteinizing hormone receptor mRNA in human endometrium and decidua. Fertil Steril. 2003;79(suppl 1): 718-723.

Minegishi T. , Tano M. , Abe Y. , Nakamura K. , Ibuki Y. , Miyamoto K. Expression of luteinizing hormone/human chorionic gonadotropin (LH/HCG) receptor mRNA in the human ovary. Mol Hum Reprod. 1997;3:101-107.

Shemesh M. , Mizrachi D. , Gurevich M. , et al. Expression of functional luteinizing hormone (LH) receptor and its messenger ribonucleic acid in bovine endometrium: LH augmentation of cAMP and inositol phosphate in vitro and human chorionic gonadotropin (hCG) augmentation of peripheral prostaglandin in vivo. Reprod Biol. 2001;1:13-32.

Zhou XL , Lei ZM , Rao CV Treatment of human endometrial gland epithelial cells with chorionic gonadotropin/luteinizing hormone increases the expression of the cyclooxygenase-2 gene. J Clin Endocrinol Metab. 1999;84:3364-3377.

Lei ZM , Reshef E. , Rao V. The expression of human chorionic gonadotropin/luteinizing hormone receptors in human endometrial and myometrial blood vessels. J Clin Endocrinol Metab. 1992;75:651-659.

Lei ZM , Toth P. , Rao CV , Pridham D. Novel coexpression of human chorionic gonadotropin (hCG)/human luteinizing hormone receptors and their ligand hCG in human fallopian tubes. J Clin Endocrinol Metab. 1993;77:863-872.

Tao YX , Heit M. , Lei ZM , Rao CV The urinary bladder of a woman is a novel site of luteinizing hormone-human chorionic gonadotropin receptor gene expression. Am J Obstet Gynecol. 1998;179:1026-1031.

Toth P. , Li X. , Rao CV , et al. Expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human uterine arteries. J Clin Endocrinol Metab. 1994;79:307-315.

10.

Griendling KK , Fuller EO , Cox RH Pregnancy-induced changes in sheep uterine and carotid arteries. Am J Physiol. 1985;248:H658-H665.

11.

Han SW , Lei ZM , Rao CV Up-regulation of cyclooxygenase-2 gene expression by chorionic gonadotropin during the differentiation of human endometrial stromal cells into decidua . Endocrinology. 1996;137:1791-1797.

12.

Lin J. , Lei ZM , Lojun S. , Rao CV , Satyaswaroop PG , Day TG Increased expression of luteinizing hormone/human chorionic gonadotropin receptor gene in human endometrial carcinomas. J Clin Endocrinol Metab . 1994;79:1483-1491.

13.

Ji Q. , Chen P. , Aoyoma C. , Liu P. Increased expression of human luteinizing hormone/human chorionic gonadotropin receptor mRNA in human endometrial cancer. Mol Cell Probes . 2002;16:269-275.

14.

Lei ZM , Rao CV , Lincoln SR , Ackermann DM Increased expression of human chorionic gonadotropin/human luteinizing hormone receptors in adenomyosis.J Clin Endocrinol Metab. 1993;76:763-768.

15.

Yantiss RK , Clement PB , Young RH Neoplastic and pre-neoplastic changes in gastrointestinal endometriosis: a study of 17 cases. Am J Surg Pathol. 2000;24:513-524.

16.

Yantiss RK , Clement PB , Young RH Endometriosis of the intestinal tract: a study of 44 cases of a disease that may cause diverse challenges in clinical and pathologic evaluation. Am J Surg Pathol. 2001;25:445-454.

17.

Vercellini P. , Fedele L. , Aimi G. , Pietropaolo G. , Consonni D. , Crosignani PG Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22:266-271.

18.

Rock JA The revised American Fertility Society classification of endometriosis: reproducibility of scoring. ZOLADEX Endometriosis Study Group. Fertil Steril . 1995;63:1108-1110.

19.

Remmele W. , Stegner HE Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 1987;8:138-140.

20.

Melis GB , Ajossa S. , Guerriero S. , et al. Epidemiology and diagnosis of endometriosis. Ann N Y Acad Sci. 1994;734: 352-357.

21.

Kjerulff KH , Erickson BA , Langenberg PW Chronic gynecological conditions reported by US women: findings from the National Health Interview Survey, 1984 to 1992 . Am J Public Health. 1996;86:195-199.

22.

Vignali M. , Infantino M. , Matrone R. , et al. Endometriosis: novel etiopathogenetic concepts and clinical perspectives. Fertil Steril. 2002;78:665-678.

23.

Valle RF Endometriosis: current concepts and therapy. Int J Gynaecol Obstet. 2002;78:107-119.

24.

Huber AV , Huber JC , Kolbus A. , et al. Systemic HCG treatment in patients with endometriosis: a new perspective for a painful disease. Wien Klin Wochenschr. 2004;116:839-843.

25.

Lincoln SR , Lei ZM , Rao CV , Yussman MA The expression of human chorionic gonadotropin/human luteinizing hormone receptors in ectopic human endometrial implants. J Clin Endocrinol Metab . 1992;75:1140-1144.