Modulation of gene expression by androgen and oestrogens in the testis andprostate of the adult rat following androgen withdrawal

Androgens are important for the structural and functional integrity of the testis and the prostate and this may in part be mediated by the aromatisati on of testosterone to oestradiol. The aim of the present study was to estab lish an in vivo model that would allow the identification of genes, the exp ression of which was regulated acutely by androgen and/or oestrogen in the male reproductive system. In rats in which the Leydig cells were ablated by administration of ethane dimethane sulfonate (EDS) 6 days earlier., testos terone esters (T) were administered from day 0 (To), and additional animals were administered either T, 17 beta -oestradiol benzoate (EB) or diethylst ilbestrol (DES) for 1 or 4 h on day 6 after EDS-treatment. Nuclear immunoex pression of the androgen receptor. (AR) was reduced or absent from the test is but unaffected in the ventral prostate following these treatments. ER be ta immunoexpression in these tissues was unchanged. Northern blot analysis showed that EB and DES as well as T administration 4 h cal licl could modul ate mRNA expression of two androgen-responsive genes, C3 and SGP-2, in the prostate. The co-administration of T or EB with the AR antagonist, flutamid e, or with the ER antagonist, ICI 182,780 (ICI), did not block the suppress ion of SGP-2 mRNA expression by T or EB. In contrast, the upregulation of C 3 mRNA expression by T was successfully antagonised by both flutamide and b y ICI. A preliminary evaluation of the expression of three Sertoli cell and five germ cell mRNAs revealed that their expression was not steroid regula ted. Our results support the hypothesis that the action of testosterone in the male reproductive system may in part be mediated by its conversion to o estradiol. This in vivo model should prove of value in future studies to id entify androgen and oestrogen regulated genes in the male reproductive syst em. (C) 2001 Elsevier Science ireland Ltd. All rights reserved.