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Combined Effects of Testosterone and Estradiol on Rat Ventral Prostrate in Organ Culture¹

Unité de Recherche sur le Métabolisme Moléculaire, et la Physio-Pathologie des Stéroides, de l'Institut National de la Santé et de la Recherche Médicale (U 33 Inserm) and ER 125 du CNRS, Hópital de Bicétre, 78 rue du Général Leclerc, 94270 Bicétre, France [T. F-C., P. R., E-E. B.], and Roussel-Uclaf, 102 route de Noisy, b.p. n. 9, 93230 Romainville, France [J. S.]

Explants of ventral prostate from normal 7- to 8-week-old Wistar rats were cultured for 144 hr in the presence of testosterone (1 nM to 1 µM) and/or estradiol (1 nM to 1 µM). Several experiments with prostates from different animals were performed at each hormone concentration. Morphology was assessed by light and electron microscopy.

In the absence of hormone, the prostatic epithelium regressed and the nonepithelial components increased. The latter included the perialveolar sheath of smooth muscular cells and the interstitial stroma with many fibroblasts, active macrophages, and a thick network of collagen. The presence of estradiol (1 nM to 10 µM) did not change this picture, whereas testosterone (1 to 100 nM) maintained the epithelial cells and prevented the increase of the perialveolar sheath and interstitial stroma so that the histological picture was like that observed in the young intact adult animal. Any concentration of estradiol (1 nM to 1 µM) associated with a physiological concentration of testosterone (1 to 4 nM) counteracted the androgen-induced inhibition of the stroma, so that both epithelium and stroma were simultaneously developed. However, when combined with supraphysiological concentrations of testosterone (10 to 100 nM), estradiol was no longer effective and the stroma remained minimal. The distribution of mucopolysaccharides and alkaline phosphatase correlated well with the morphological observations.

The ratio of estradiol to testosterone is therefore insufficient to explain whether or not interstitial tissue will develop and a critical factor appears to be the absolute concentration of testosterone. Preliminary observations have indicated that diethylstilbestrol does not mimic estradiol action and that tamoxifen is neither an agonist nor an antagonist of the estradiol effect. Accordingly, the estradiol effect obtained at physiological concentrations of testosterone does not seem to be mediated through active participation of a classical estradiol receptor.

¹ Presented at the John E. Fogarty International Center Conference on Hormones and Cancer, March 29 to 31, 1978, Bethesda, Md.