ABSTRACT
The influence of s-triazine compounds (atrazine, prometryne and deethylatrazine) on testosterone conversion and 5 alpha-dihydrotestosterone-receptor complex formation was studied in vitro and in vivo in the rat prostate. A marked in vitro influence of atrazine and prometryne (from 0.465 to 1.392 mumol) and their mixtures (in total concentration, 0.928 mumol) on 5 alpha-dihydrotestosterone formation was detected. 5 alpha-Dihydrotestosterone-specific receptor complex formation was inhibited in vitro by ca. 0.5 mumol of atrazine or deethylatrazine and only in vivo by 6 mg of atrazine 100 g-1 body wt. daily during 7 days in the prostate cytosol. The inhibition of the enzymic activities responsible for testosterone conversion and steroid hormone-receptor complex formation was non-competitive and reversible, and s-triazine compounds act as antiandrogens.
Subject(s)
Atrazine/analogs & derivatives , Atrazine/toxicity , Prometryne/toxicity , Prostate/drug effects , Receptors, Androgen/metabolism , Testosterone/metabolism , Androstadienes/metabolism , Androstane-3,17-diol/metabolism , Animals , Atrazine/administration & dosage , Binding Sites , Cytosol/drug effects , Cytosol/pathology , Etiocholanolone/analogs & derivatives , Etiocholanolone/metabolism , In Vitro Techniques , Male , Prometryne/administration & dosage , Prostate/metabolism , Prostate/pathology , Rats , Rats, Inbred F344 , Receptors, Androgen/drug effects , StereoisomerismABSTRACT
The metabolism of testosterone in the rat ventral prostate, anterior pituitary, basal hypothalamus and amygdala was studied in vitro under the influence of vitamin B6 compounds. The influence of these compounds on the activity of 5 alpha-reductase (5 alpha-R), 3 alpha- and 17 beta-hydroxysteroid dehydrogenase (3 alpha-HSD, 17 beta-HSD) was determined for all the examined tissues. Pyridoxine hydrochloride significantly increased the activity of 5 alpha-R, 3 alpha- and 17 beta-HSD, but pyridoxal hydrochloride had an inhibitory influence on 5 alpha-R and showed no effect on 3 alpha-HSD activity at the prostate level. Male rat anterior pituitary, basal hypothalamus or amygdala incubated with pyridoxal phosphate and pyridoxal hydrochloride showed modified enzymatic activities. Pyridoxal hydrochloride showed an inhibitory effect on 5 alpha-R in the rat pituitary and basal hypothalamus as well as in the rat prostate.