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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

Department of Veterinary Biosciences (C.A.O., Q.Z., K.C., R.N., D.E.K., G.L.J., M.N., R.A.H.), University of Illinois, Urbana, Illinois 61802; and Departments of Morphology and Physiology (C.A.O., L.R.F.), Federal University of Minas Gerais, Belo Horizonte-MG, Brazil 31270-901

Address all correspondence and requests for reprints to: Dr. Rex A. Hess, Veterinary Biosciences, University of Illinois, 2001 South Lincoln, Urbana, Illinois 61802-6199. E-mail: . r-hess{at}uiuc.edu

Male rats, 30 d old, were treated with the antiestrogen ICI 182,780 (3–150 d) to determine sequences of events leading to testicular atrophy and infertility. Plasma testosterone and LH concentrations were unchanged. ICI 182,780 induced dilation of efferent ductules as early as 3 d post treatment, and the dilation increased over time, resulting in an overall increase of 200% in tubule diameter. A gradual reduction in height of the ductule epithelium was observed; however, the microvilli height increased up to d 73 but subsequently decreased. A transient increase in lysosomes in nonciliated cells was seen from d 15 to d 100. Testicular weight increased by d 45 and seminiferous tubules were dilated by d 52. These effects on testes persisted until d 100, but on d 150 the weight decreased and severe atrophy was observed. These testicular effects were probably owing to accumulation of fluid following inhibition of reabsorption in the efferent ductules, similar to the ER- knockout mouse. In agreement with this conclusion, there was a decrease in Na+-H+ exchanger-3 mRNA and protein, which is consistent with previous studies showing that ER is required for expression of Na+-H+ exchanger-3 and ultimately fluid reabsorption in the efferent ductules.

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