Effect of a diphenylethylenediamine platinum complex on steroidogenesis in rats

J Steroid Biochem Mol Biol. 1996 May;58(2):243-8. doi: 10.1016/0960-0760(96)00035-0.

Abstract

Although less cytotoxic, the new platinum complex [meso-1,2-bis(2,6-difluoro-4-hydroxyphenyl)-ethylenediamine]sulfatopl atinum (II) (2) is equipotent to cisplatin (1) in the 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 mumol/kg s.c.) decreased plasma testosterone level in male rats by 90% (1, day 3) and 80% (2, day 7). Luteinizing hormone level remained unchanged in intact and in ovariectomized rats. The activities of the following testicular enzymes were decreased (day 7): cholesterol side-chain cleavage enzyme (1: 33%; 2: 36%), 3 beta-hydroxysteroid dehydrogenase/delta 4,delta 5-isomerase (1: 31%; 2: 48%) and 17 alpha-hydroxylase/17,20-lyase (1: 21%; 2: 15%). Testicular microsomal cytochrome P450 content was also diminished (1: 60%; 2: 49%, day 7). Corticosterone level in plasma and biosynthesis in adrenal explants was not affected, indicating the selectivity of action at the gonadal level. In vitro, neither 1 nor 2 (2 and 20 microM) influenced binding of human chorionic gonadotropin 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / drug effects
  • 3-Hydroxysteroid Dehydrogenases / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / toxicity
  • Chorionic Gonadotropin / metabolism
  • Cisplatin / analogs & derivatives
  • Cisplatin / pharmacology
  • Corticosterone / blood
  • Corticosterone / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Ethylenediamines / pharmacology*
  • Ethylenediamines / toxicity
  • Female
  • Humans
  • Luteinizing Hormone / blood
  • Luteinizing Hormone / metabolism
  • Male
  • Organoplatinum Compounds / pharmacology*
  • Ovariectomy
  • Platinum / pharmacology*
  • Platinum / toxicity
  • Prolactin / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, LH / drug effects
  • Receptors, LH / metabolism
  • Steroids / metabolism*
  • Testis / drug effects
  • Testis / metabolism
  • Testosterone / metabolism

Substances

  • (1,2-bis(2,6-difluoro-4-hydroxyphenyl)ethylenediamine)sulfatoplatinum(II)
  • Antineoplastic Agents
  • Chorionic Gonadotropin
  • Ethylenediamines
  • Organoplatinum Compounds
  • Receptors, LH
  • Steroids
  • Testosterone
  • Platinum
  • Prolactin
  • Luteinizing Hormone
  • Cytochrome P-450 Enzyme System
  • 3-Hydroxysteroid Dehydrogenases
  • Cisplatin
  • Corticosterone