Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Dec;83(12):1730–1734. doi: 10.1054/bjoc.2000.1507

Regulation of endometrial cancer cell growth by luteinizing hormone (LH) and follicle stimulating hormone (FSH)

S Davies 1, C M R Bax 1, E Chatzaki 2, T Chard 3, R K Iles 1
PMCID: PMC2363464  PMID: 11104573

Abstract

Gonadotrophin releasing hormone analogues (GnRHa) have been used to treat recurrent endometrial cancer. However, the mode of action is uncertain. Our previous studies showed no direct effect of GnRHa on endometrial cancer cell growth in vitro. We have now examined the effect of luteinizing hormone (LH) and follicle stimulating hormone (FSH) on endometrial cancer cell growth. The aim was to determine whether suppression of pituitary LH and FSH by GnRHa could explain the tumour regression seen in up to 44% of patients treated with this drug. We show that recombinant human LH and FSH (rhLH and rhFSH) produce a concentration dependent stimulation of the endometrial cancer cell line HEC-1A, in serum-free medium (maximum increase of 62 and 50% respectively relative to untreated controls). This increase is equivalent to that obtained by addition of 10% newborn calf serum. Growth of the Ishikawa cell line in culture increases in the presence of rhLH (maximum increase of 67%) but not with rhFSH. Using RT-PCR, we show that the Ishikawa cell line intermittently expresses receptor mRNA of LH but not of FSH; there is no expression of either mRNA by HEC-1A. Classically, both LH and FSH act via cAMP linked membrane receptors. However, neither rhLH nor rhFSH elicit cAMP production in either of our endometrial cancer cell lines. Thus, although a growth response to LH and FSH can be shown, and some cells express the LH receptor, stimulation appears to be via a pathway separate from that of the classical gonadotrophin receptor. © 2000 Cancer Research Campaign http://www.bjcancer.com

Keywords: endometrial cancer, luteinizing hormone (LH), follicle stimulating hormone (FSH), GnRH analogues

Full Text

The Full Text of this article is available as a PDF (220.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brown B. L., Albano J. D., Ekins R. P., Sgherzi A. M. A simple and sensitive saturation assay method for the measurement of adenosine 3':5'-cyclic monophosphate. Biochem J. 1971 Feb;121(3):561–562. doi: 10.1042/bj1210561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chatzaki E., Bax C. M., Eidne K. A., Anderson L., Grudzinskas J. G., Gallagher C. J. The expression of gonadotropin-releasing hormone and its receptor in endometrial cancer, and its relevance as an autocrine growth factor. Cancer Res. 1996 May 1;56(9):2059–2065. [PubMed] [Google Scholar]
  3. Dirnhofer S., Berger C., Hermann M., Steiner G., Madersbacher S., Berger P. Coexpression of gonadotropic hormones and their corresponding FSH- and LH/CG-receptors in the human prostate. Prostate. 1998 May 15;35(3):212–220. doi: 10.1002/(sici)1097-0045(19980515)35:3<212::aid-pros7>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  4. Dowsett M., Cantwell B., Lal A., Jeffcoate S. L., Harris A. L. Suppression of postmenopausal ovarian steroidogenesis with the luteinizing hormone-releasing hormone agonist goserelin. J Clin Endocrinol Metab. 1988 Apr;66(4):672–677. doi: 10.1210/jcem-66-4-672. [DOI] [PubMed] [Google Scholar]
  5. Emons G., Schröder B., Ortmann O., Westphalen S., Schulz K. D., Schally A. V. High affinity binding and direct antiproliferative effects of luteinizing hormone-releasing hormone analogs in human endometrial cancer cell lines. J Clin Endocrinol Metab. 1993 Dec;77(6):1458–1464. doi: 10.1210/jcem.77.6.8263128. [DOI] [PubMed] [Google Scholar]
  6. Gallagher C. J., Oliver R. T., Oram D. H., Fowler C. G., Blake P. R., Mantell B. S., Slevin M. L., Hope-Stone H. F. A new treatment for endometrial cancer with gonadotrophin releasing-hormone analogue. Br J Obstet Gynaecol. 1991 Oct;98(10):1037–1041. doi: 10.1111/j.1471-0528.1991.tb15343.x. [DOI] [PubMed] [Google Scholar]
  7. Gudermann T., Birnbaumer M., Birnbaumer L. Evidence for dual coupling of the murine luteinizing hormone receptor to adenylyl cyclase and phosphoinositide breakdown and Ca2+ mobilization. Studies with the cloned murine luteinizing hormone receptor expressed in L cells. J Biol Chem. 1992 Mar 5;267(7):4479–4488. [PubMed] [Google Scholar]
  8. Imai A., Ohno T., Iida K., Fuseya T., Furui T., Tamaya T. Presence of gonadotropin-releasing hormone receptor and its messenger ribonucleic acid in endometrial carcinoma and endometrium. Gynecol Oncol. 1994 Oct;55(1):144–148. doi: 10.1006/gyno.1994.1264. [DOI] [PubMed] [Google Scholar]
  9. Jeyarajah A. R., Gallagher C. J., Blake P. R., Oram D. H., Dowsett M., Fisher C., Oliver R. T. Long-term follow-up of gonadotrophin-releasing hormone analog treatment for recurrent endometrial cancer. Gynecol Oncol. 1996 Oct;63(1):47–52. doi: 10.1006/gyno.1996.0276. [DOI] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Labarca C., Paigen K. A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980 Mar 1;102(2):344–352. doi: 10.1016/0003-2697(80)90165-7. [DOI] [PubMed] [Google Scholar]
  12. Lamharzi N., Halmos G., Jungwirth A., Schally A. V. Decrease in the level and mRNA expression of LH-RH and EGF receptors after treatment with LH-RH antagonist cetrorelix in DU-145 prostate tumor xenografts in nude mice. Int J Oncol. 1998 Sep;13(3):429–435. doi: 10.3892/ijo.13.3.429. [DOI] [PubMed] [Google Scholar]
  13. Lin J., Lei Z. M., Lojun S., Rao C. V., Satyaswaroop P. G., Day T. G. Increased expression of luteinizing hormone/human chorionic gonadotropin receptor gene in human endometrial carcinomas. J Clin Endocrinol Metab. 1994 Nov;79(5):1483–1491. doi: 10.1210/jcem.79.5.7962347. [DOI] [PubMed] [Google Scholar]
  14. Nagamani M., Doherty M. G., Smith E. R., Chandrasekhar Y. Increased bioactive luteinizing hormone levels in postmenopausal women with endometrial cancer. Am J Obstet Gynecol. 1992 Dec;167(6):1825–1830. doi: 10.1016/0002-9378(92)91782-6. [DOI] [PubMed] [Google Scholar]
  15. Nakajima-Iijima S., Hamada H., Reddy P., Kakunaga T. Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6133–6137. doi: 10.1073/pnas.82.18.6133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nishida M., Kasahara K., Kaneko M., Iwasaki H., Hayashi K. [Establishment of a new human endometrial adenocarcinoma cell line, Ishikawa cells, containing estrogen and progesterone receptors]. Nihon Sanka Fujinka Gakkai Zasshi. 1985 Jul;37(7):1103–1111. [PubMed] [Google Scholar]
  17. Simon W. E., Albrecht M., Hänsel M., Dietel M., Hölzel F. Cell lines derived from human ovarian carcinomas: growth stimulation by gonadotropic and steroid hormones. J Natl Cancer Inst. 1983 May;70(5):839–845. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES