EFFECT OF A DIPHENYLETHYLENEDIAMINE PLATINUM COMPLEX ON STEROIDOGENESIS IN RATS

Although less cytotoxic, the new platinum complex hydroxyphenyl)-ethyl enediamine]sulfatoplatinum(II) (2) is equipotent to cisplatin (1) in t he oestrogen-dependent MXT mammary tumour of the mouse. As this may be due to oestrogen level-lowering properties, we compared the effect of 1 and 2 on steroidogenesis in the rat. A single dose of 1 and 2 (20 m u mol/kg s.c.) decreased plasma testosterone level in male rats by 90% (1, day 3) and 80% (2, day 7). Luteinizing hormone level remained unc hanged in intact and in ovariectomized rats. The activities of the fol lowing testicular enzymes were decreased (day 7): cholesterol side-cha in cleavage enzyme (1: 33%; 2: 36%), 3 beta-hydroxysteroid dehydrogena se/Delta 4,Delta 5-isomerase (1: 31%; 2: 48%) and 17 alpha-hydroxylase /17,20-lyase (1: 21%; 2: 15%). Testicular microsomal cytochrome P450 c ontent was also diminished (1: 60%; 2: 49%, day 7). Corticosterone lev el in plasma and biosynthesis in adrenal explants was not affected, in dicating the selectivity of action at the gonadal level. In vitro, nei ther 1 nor 2 (2 and 20 mu M) influenced binding of human chorionic gon adotropin to testis interstitial cells during an observation period up to 21 h. These results suggest that 1 and 2 act at the gonadal level by inhibiting the expression of the steroidogenic enzymes. They do not , however, inactivate the luteinizing hormone receptor. Copyright (C) 1996 Elsevier Science Ltd.