Molecular and Cellular Endocrinology 329 (2010) 56–61
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Molecular and Cellular Endocrinology
journal homepage: www.elsevier.com/locate/mce
Review
Are gonadotrophins tumorigenic—A critical review of
clinical and experimental data
Ilpo Huhtaniemi
Department of Surgery and Cancer, IRDB Building, Imperial College London, Hammersmith Campus, Du Cane Road,
London W12 0NN, UK
article info
Article history:
Received 26 May 2009
Received in revised form 12 April 2010
Accepted 26 April 2010
Keywords:
Gonadotrophin receptors
Ovarian cancer
Breast cancer
Prostatic cancer
Prolactinoma
Adrenal tumors
abstract
The growth of many gonadal and extragonadal tumors is stimulated by gonadal sex hormones. Because
gonadal hormone production is regulated by pituitary gonadotrophins, the latter hormones can be
considered as indirect tumor promoters. In addition, there is a growing body of evidence that both
gonadal (e.g. ovarian cancer) and extragonadal (e.g. breast, uterus, prostate and adrenal) tumors express
gonadotrophin receptors, indicating the possibility of a direct tumorigenic role for FSH and LH. The pur-
pose of this brief review is to present a critical evaluation of the current information, both clinical and
experimental, about the direct involvement of gonadotrophins in the induction and growth of gonadal
and extragonadal tumors.
© 2010 Elsevier Ireland Ltd. All rights reserved.
Contents
1. Introduction .......................................................................................................................................... 56
2. Expression and function of gonadotrophin receptors in human tumors ........................................................................... 57
2.1. Ovarian tumors ............................................................................................................................... 57
2.2. Extragonadal tumors ......................................................................................................................... 58
3. Animal models of gonadotrophin-dependent tumorigenesis ....................................................................................... 59
3.1. Ovarian and testicular tumors ............................................................................................................... 59
3.2. Extragonadal tumors ......................................................................................................................... 59
4. Conclusions .......................................................................................................................................... 59
References ........................................................................................................................................... 59
1. Introduction
When we consider the potential roleof gonadotrophins as tumor
promoters, two alternative mechanisms are possible. Firstly, FSH
and LH act indirectly by stimulating ovarian and testicular produc-
tion of sex hormones, which then exert their tumorigenic actions
on a variety of hormone-dependent benign and malignant tumors,
including those of the gonads, uterus, breast, prostate and pituitary
E-mail address: ilpo.huhtaniemi@imperial.ac.uk.
gland. Secondly, gonadotrophins may act directly through their
receptors whose expression has been documented in both gonadal
and extragonadal tumors. While the former mechanism is well-
established in many hormone-dependent neoplasias, for example
in premenopausal breast cancer and in prostate cancer, the latter
alternative remains contentious. The purpose of this article is to
present a brief critical review of our current knowledge about the
putative direct involvement of gonadotrophins in the induction and
growth of tumors in clinical settings, as well as to review some
of the available experimental models of gonadotrophin-dependent
tumorigenesis.
0303-7207/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.mce.2010.04.028