Effects of Tamoxifen on Plasma Concentrations of Testosterone and Gonadotrophins in the Male Rat

Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545, U.S.A. (Received 2% March 1978) Tamoxifen (trans 1-(p-β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene; ICI 46,474) is both a potent antioestrogen and a weak oestrogen (Harper & Walpole, 1967) and is thought to act by inhibiting the binding of oestradiol to its cytoplasmic receptor (Jordan & Koerner, 1975). Chronic treatment with tamoxifen causes atrophy of the male accessory reproductive glands and the testicular germinal epithelium in the rat (Harper & Walpole, 1967) and the dog (M. Mason, unpublished data), as well as depression of the plasma concentration of testosterone in the latter species (M. Mason & A. Bartke, unpublished data). A direct inhibitory effect of tamoxifen on testicular steroidogenesis was suspected because treatment of female rats with tamoxifen increases, rather than decreases, the plasma concentration of luteinizing hormone (LH; Watson, Anderson, Alam, O'Grady & Heald, 1975). The possibility that an antioestrogen might act directly is of interest since