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EMSG17: Identification of Biomedical Endpoints of Oestrogen Action in the Male Rat With Possible Confirmation in Primate Model and in Man

Principal Investigator

Prof. Richard Sharpe
MRC - Human Reproductive Sciences Unit
Centre for Reproductive Biology
The University of Edinburgh Academic Centre
49 Little France Crescent
Old Dalkeith Road
Edinburgh EH16 4SB
Tel: +44-131-242-6387
Fax: +44-131-242-6231
r.sharpe@hrsu.mrc.ac.uk

Collaborators

Prof. Philippa Saunders- MRC
p.saunders@hrsu.mrc.ac.uk

Description

The objective of the project was to identify biochemical endpoints of oestrogen action in the male rat during foetal and neonatal development, which may have potential for monitoring the level of “oestrogen” exposure of individual animals, either in infancy or adulthood.

Related Publications

Sharpe R.M., M. Walker, M.R. Millar, K. Morris, C. McKinnell, P.T.K. Saunders, H.M. Fraser. Effect of neonatal gonadotropin-releasing hormone antagonist administration on sertoli cell number and testicular development in the marmoset: comparison with the rat. Biology of Reproduction 2000 Vol. 62, Issue 6, 685-93, 4 January 2000. Sharpe, R.M., J.S. Fisher, P.T.K. Saunders, G. Majdic, M.R. Millar, P. Parte, J.B. Kerr and K.J. Turner. Estrogen effects on development and function of testis. Germ Cell Development, Division, Disruption and Death (Editor B.R. Zirkin), Serono Symposia, Springer Verlag, New York, pp 167-177, 1998. Jane S. Fisher, Katie J; Turner, Hamish M. Fraser, Philippa T.K. Saunder, Dennis Brown and Richard Sharpe. Immunoexpression of Aquaporin-1 in the Efferent Ducts of the Rat and Marmoset Monkey during Development, Its Modulation by Estrogens, and its Possible Role in Fluid Resorption. Endocrinology : Vol. 139, Issue 9, 3935-3945, September 1998. Atanassova, N., C. McKinnell, M. Walker, K.J. Turner, J.S. Fisher, M. Morley, M.R. Millar, N.P. Groome, R.M. Sharpe Permanent effects of neonatal estrogen exposure in rats on reproductive hormone levels, sertoli cell number and the efficiency of spermatogenesis in adulthood. Endocrinology Vol. 140, Issue 11, 5364-5373, November 1999. Sharpe, R.M., C. McKinnell, N. Atanassova, K. Williams, K.J. Turner, P.T.K. Saunders, M. Walker, M.R. Millar, J.S. Fisher. Interaction of androgens and oestrogens in development of the testis and male reproductive tract. In: Testis, Epididymis and Technologies in the Year 2000. 11th European Workshop on Molecular and Cellular Endocrinology of the Testis. (Editors B. Jegou, C. Pineau, J. Saez) Springer Verlag, Heidelberg, pp 173-195, 2000. Atanassova, N., C. McKinnell, K.J. Turner, M. Walker, J.S. Fisher, M. Morley, M.R. Millar, N.P. Groome, R.M. Sharpe. Comparative effects of neonatal exposure of male rats to potent and weak (environmental) estrogens on spermatogenesis at puberty and the relationship to adult testis size and fertility: evidence for stimulatory effects of low estrogen levels. Endocrinology Vol. 141, Issue 10, 3898-3907, October 2000. Atanassova, N., C. McKinnell, K. Williams, K.J. Turner, J.S. Fisher, P.T.K. Saunders, M.R. Millar, R.M. Sharpe. Age-, cell-, and region-specific immunoexpression of estrogen receptor a (but not estrogen receptor ß) during postnatal development of the epididymis and vas deferens of the rat and disruption of this pattern by neonatal treatment with diethylstilbestrol. Endocrinology : Vol. 142, Issue 2, 874-886, February 2001. McKinnell, C., N. Atanassova, K. Williams, J.S. Fisher, M. Walker, K.J. Turner, P.T.K. Saunders, R.M. Sharpe .Suppression of androgen action and the induction of gross abnormalities of the reproductive tract in male rats treated neonatally with diethylstilbestrol. Journal of Andrology : Vol. 22, Issue 2, 323-338, March-April 2001. Williams, K., C. McKinnell, P.T.K. Saunders, M. Walker, J.S. Fisher, K.J. Turner, N. Atanassova, R.M. Sharpe. Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: evidence for the importance of the androgen-oestrogen balance and assessment of the relevance to man. Human Reproduction Update Vol. 7, Issue 3, 236-247, May-June 2001. Williams K, Saunders PTK, Atanassova N, Fisher JS, Turner KJ, Millar MR, McKinnell C & Sharpe RM. Induction of progesterone receptor immunoexpression in stromal tissue throughout the male reproductive tract after neonatal oestrogen treatment of rats., Molecular & Cellular Endocrinology : Vol. 164, Issues 1-2, 117-131, 20 June 2000.

LRI funding: €268,908 (via ECETOC) Joint Funding with MRC, EU, Royal Society and Astra-Zeneca.

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