REGULATION OF SEMICARBAZIDE-SENSITIVE AMINE OXIDASE ACTIVITY BY TESTOSTERONE: ROLE OF ANDROGEN RECEPTOR, ORNITHINE DECARBOXYLASE AND NITRIC OXIDE SYNTHASES
MILENA MISHONOVA1, HRISTO GAGOV1*
1 Department of Animal and human physiology, Faculty of Biology, 8 Dragan Tzankov, Sofia University St. Kliment Ohridski, Sofia, Bulgaria
* Corresponding author: e-mail: hgagov@uni-sofia.bg
Keywords: testosterone, liver, kidney, polyamines, histamine, nitric oxide
Abstract: Semicarbazide sensitive amine oxidase (SSAO; E.C.1.4.3.6) also known as diamine oxidase (DAO) or vascular adhesion protein-1 (VAP-1) is a key enzyme of the catabolism of polyamines and is partially responsible for the degradation of histamine. Its activity was assayed in male immature rat liver and kidney. It is known that testosterone (T) activates SSAO in murine kidney, an effect that might depend on the intracellular level of polyamines. The aim of this research is to study the participation of androgen receptor, ornithine decarboxylase (ODC) and nitric oxide synthases (NOS) in testosterone regulation of DAO. The rats were treated i.p. 4 hours before measurements with T, T + hydroxyflutamide (HF), an androgen receptor antagonist, T + difluoromethylornithine (DFMO), an inhibitor of ODC or one of two selective NOS inhibitors. It was observed that i) T significantly increased DAO activity in rat kidney; ii) treatment with HF abolished this effect of T; iii) the presence of DFMO had not significant effect on T-dependent influence on DAO activity; iv) the application of NOS inhibitors reduced DAO activity of rat liver and kidney and v) the simultaneously applied T and NOS inhibitor left DAO activity at control level in liver and significantly decreased it in kidney. It is concluded that T may regulate the net (microsomal and soluble) DAO activity in rat kidney and to some extend in rat liver by a mechanism, which includes androgen receptor binding and NO as a downstream signal molecule.