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Estrogen and Spermatogenesis¹

Prince Henry’s Institute of Medical Research (L.O., K.M.R., M.E.J., E.R.S.) and Department of Biochemistry (K.M.R.), Monash University, Clayton, 3168, Victoria, Australia

Although it has been known for many years that estrogen administration has deleterious effects on male fertility, data from transgenic mice deficient in estrogen receptors or aromatase point to an essential physiological role for estrogen in male fertility. This review summarizes the current knowledge on the localization of estrogen receptors and aromatase in the testis in an effort to understand the likely sites of estrogen action. The review also discusses the many studies that have used models employing the administration of estrogenic substances to show that male fertility is responsive to estrogen, thus providing a mechanism by which inappropriate exposure to estrogenic substances may cause adverse effects on spermatogenesis and male fertility. The reproductive phenotypes of mice deficient in estrogen receptors and/or ß and aromatase are also compared to evaluate the physiological role of estrogen in male fertility. The review focuses on the effects of estrogen administration or deprivation, primarily in rodents, on the hypothalamo-pituitary-testis axis, testicular function (including Leydig cell, Sertoli cell, and germ cell development and function), and in the development and function of the efferent ductules and epididymis. The requirement for estrogen in normal male sexual behavior is also reviewed, along with the somewhat limited data on the fertility of men who lack either the capacity to produce or respond to estrogen. This review highlights the ability of exogenous estrogen exposure to perturb spermatogenesis and male fertility, as well as the emerging physiological role of estrogens in male fertility, suggesting that, in this local context, estrogenic substances should also be considered "male hormones."

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				Q. Zhou, R. Nie, G. S. Prins, P. T. K. Saunders, B. S. Katzenellenbogen, and R. A. Hess Localization of Androgen and Estrogen Receptors in Adult Male Mouse Reproductive Tract J Androl, November 1, 2002; 23(6): 870 - 881. [Abstract] [Full Text] [PDF]

				M. Kos, S. Denger, G. Reid, and F. Gannon Upstream Open Reading Frames Regulate the Translation of the Multiple mRNA Variants of the Estrogen Receptor alpha J. Biol. Chem., September 27, 2002; 277(40): 37131 - 37138. [Abstract] [Full Text] [PDF]

				K. L. BRITT, J. KERR, L. O'DONNELL, M. E. E. JONES, A. E. DRUMMOND, S. R. DAVIS, E. R. SIMPSON, and J. K. FINDLAY Estrogen regulates development of the somatic cell phenotype in the eutherian ovary FASEB J, September 1, 2002; 16(11): 1389 - 1397. [Abstract] [Full Text] [PDF]

				K. M. Robertson, L. O'Donnell, E. R. Simpson, and M. E. E. Jones The Phenotype of the Aromatase Knockout Mouse Reveals Dietary Phytoestrogens Impact Significantly on Testis Function Endocrinology, August 1, 2002; 143(8): 2913 - 2921. [Abstract] [Full Text] [PDF]

				M. H. Tong and W.-C. Song Estrogen Sulfotransferase: Discrete and Androgen-Dependent Expression in the Male Reproductive Tract and Demonstration of an in Vivo Function in the Mouse Epididymis Endocrinology, August 1, 2002; 143(8): 3144 - 3151. [Abstract] [Full Text] [PDF]

				R. Luboshitzky, Z. Shen-Orr, R. Nave, S. Lavi, and P. Lavie Melatonin Administration Alters Semen Quality in Healthy Men J Androl, July 1, 2002; 23(4): 572 - 578. [Abstract] [Full Text] [PDF]

				J. C. Achermann, G. Ozisik, J. J. Meeks, and J. L. Jameson Genetic Causes of Human Reproductive Disease J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2447 - 2454. [Full Text] [PDF]

				P. T. K. Saunders, M. R. Millar, S. Macpherson, D. S. Irvine, N. P. Groome, L. R. Evans, R. M. Sharpe, and G. A. Scobie ER{beta}1 and the ER{beta}2 Splice Variant (ER{beta}cx/{beta}2) Are Expressed in Distinct Cell Populations in the Adult Human Testis J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2706 - 2715. [Abstract] [Full Text] [PDF]

				C. A. Oliveira, Q. Zhou, K. Carnes, R. Nie, D. E. Kuehl, G. L. Jackson, L. R. Franca, M. Nakai, and R. A. Hess ER Function in the Adult Male Rat: Short- and Long-Term Effects of the Antiestrogen ICI 182,780 on the Testis and Efferent Ductules, without Changes in Testosterone Endocrinology, June 1, 2002; 143(6): 2399 - 2409. [Abstract] [Full Text] [PDF]

				G. Stelzer and J. Don Atce1: A Novel Mouse Cyclic Adenosine 3',5'-Monophosphate-Responsive Element-Binding Protein-Like Gene Exclusively Expressed in Postmeiotic Spermatids Endocrinology, May 1, 2002; 143(5): 1578 - 1588. [Abstract] [Full Text] [PDF]

				Z.-x. Zhou, B. He, S. H. Hall, E. M. Wilson, and F. S. French Domain Interactions between Coregulator ARA70 and the Androgen Receptor (AR) Mol. Endocrinol., February 1, 2002; 16(2): 287 - 300. [Abstract] [Full Text] [PDF]

				R.I. McLachlan, L. O'Donnell, S.J. Meachem, P.G. Stanton, D.M. de Kretser, K. Pratis, and D.M. Robertson Identification of Specific Sites of Hormonal Regulation in Spermatogenesis in Rats, Monkeys, and Man Recent Prog. Horm. Res., January 1, 2002; 57(1): 149 - 179. [Abstract] [Full Text] [PDF]