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
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Brown BL, Albano JD, Ekins RP and Sgherzi AM (1971) A simple and sensitive saturation assay method for the measurement of adenosine 3′:5′-cyclic monophosphate. Biochem J 121( 3): 561–562
Chatzaki E, Bax CMR, Eidne KA, Anderson L, Grudzinskas JG and Gallagher CJ (1996) The expression of gonadotrophin releasing hormone and its receptor in endometrial cancer and its relevance as an autocrine growth factor. Cancer Res 56: 2059–2065
Dirnhofer S, Berger C, Hermann M, Steiner G, Madersbacher S and Berger P (1998) Coexpression of gonadotrophic hormones and their corresponding FSH and LH/CG receptors in the human prostate. The Prostate 35: 212–220
Dowsett M, Cantwell B, Anshumala L, Jeffocate SL and Harris AL (1988) Suppression of postmenopausal ovarian steroidogenesis with the luteinising hormone-releasing hormone agonist goserelin. J Clin Endocrinol Metabolism 66: 672–677
Emons G, Schroder B, Ortmann O, Westphalen S, Schulz KD and Schally AV (1993) High affinity binding and direct antiproliferative effects of luteinising hormone-releasing hormone analogs in human endometrial cancer cell lines. J Clin Endocrinol Metabolism 77(6): 1458–1464
Farndale RW, Allan LM and Martin BR (1992) Adenylate cyclase and cAMP (Chapter 4). In: Milligan G (ed), Signal Transduction: A Practical Approach. OUP, Oxford
Gallagher CJ, Oliver RTD, Oram DH, Fowler CG, Blake PR, Mantell BS, Slevin ML and Issacs NW (1991) A new treatment for endometrial cancer with gonadotrophin releasing hormone analogue. Br J Obst Gynaecol 98: 1037–1041
Grudermann T, Birnbaumer M and Birnbaumer L (1992) Evidence for dual coupling of the murine luteinising hormone receptor to adenylate cyclase and phosphoinositol breakdown and Ca2+ mobilisation. J Biol Chem 267: 4479–4488
Imai A, Ohno T, Iida K, Fuseya T, Furui T and Tamaya T (1994) Presence of gonadotrophin-releasing hormone receptor and its messenger ribonucleic acid in endometrial carcinoma and endometrium. Gynaecol Oncol 55( 1): 144–148
Jeyarajah AR, Gallagher CJ, Blake PR, Oram DH, Dowsett M, Fisher C and Oliver RTD (1996) Long term follow-up of Gonadotrophin-releasing hormone analog treatment for recurrent endometrial cancer. Gyn Oncol 63: 47–52
Labarca C and Paigen K (1980) A simple and sensitive DNA assay procedure. Analytical Biochemistry 102: 344–352
Lamharzi N, Halmos G, Jungwirth A and Schally AV (1998) Decrease in the level and mRNA expression of LH-RH and EGF receptors after treatment with LH-RH antagonist cetroelix in DU-145 prostate tumour xenografts in nude mice. Int J Oncol 13(3): 429–435
Lin J, Lei ZM, Lojun S, Rao CV, Satyaswaroop PG and Day TG (1994) Increased expression of luteinising hormone/human chorionic gonadotrophin receptor gene in human endometrial carcinomas. J Clin Endocrinol Met 79( 5): 1483–1491
Lowry O, Rosebrough NJ and Farr AL (1951) Protein determination with the Folin phenol reagent. J Biol Chem 193: 265–275
Nagamani M, Doherty MG, Smith ER and Chandrasekhar Y (1993) Increased bioactive luteinising hormone levels in postmenopausal women with endometrial cancer. Am J Obst Gynaecol 167: 1825–1830
Nakajima-Iijima S, Hamada H, Reddy P and Kakunaga T (1985) Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci USA 82: 6133–6137
Nishida M, Kasahara K, Kaneto M, Iwasaki H and Hayashi K (1985) Establishment of a new human adenocarcinoma cell line, Ishikawa cells, containing oestrogen and progesterone receptors. Acta Obstetrics and Gynaecology Journal of Japan 37: 1103–1111
Simon WE, Albrecht M, Hansel M, Dietel M and Holzel F (1983) Cell lines derived from human ovarian carcinomas: growth stimulation by gonadotropic and steroid hormones. J Natl Cancer Inst 70( 5): 839–845
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Davies, S., Bax, C., Chatzaki, E. et al. Regulation of endometrial cancer cell growth by luteinizing hormone (LH) and follicle stimulating hormone (FSH). Br J Cancer 83, 1730–1734 (2000). https://doi.org/10.1054/bjoc.2000.1507
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1054/bjoc.2000.1507
Keywords
This article is cited by
-
A novel role of follicle-stimulating hormone (FSH) in various regeneration-related functions of endometrial stem cells
Experimental & Molecular Medicine (2022)
-
The Effectiveness of Various Chemotherapeutic Agents in Cancer Treatment
Current Pharmacology Reports (2022)
-
Mutation status coupled with RNA-sequencing data can efficiently identify important non-significantly mutated genes serving as diagnostic biomarkers of endometrial cancer
BMC Bioinformatics (2017)
-
The levels of the sex hormones are not different between type 1 and type 2 endometrial cancer
Scientific Reports (2016)
-
CGB activates ERK and AKT kinases in cancer cells via LHCGR-independent mechanism
Tumor Biology (2014)
