Effect of testosterone on purine synthesis de novo in rat perineal muscle in vivo

Abstract

We examined in vivo the influence of testosterone on purine synthetis de nov, in the levator ani and gastrocnemius muscles of the rat. The hypoxanthine, adenine and guanine contents and the rate of incorporation of [ 14C]formate into these purine bases were determined in castrated adult and prepubertal rats (groups 1 and 2) both before and after orchiectomy and, in the second case, at different times after testosterone treatment. Substantially similar behavior was found in both groups, with some specific differences. The results showed an increase in the basal levels after castration (except for a dramatic decrease in adenine and a rise in the Gua/Ade molar ratio in prepubertal rats) and a return to basal levels after hormone administration, which was also accompanied by variations in the Gua/Ade molar ratio. The kinetics of purine nucleotide synthesis de novo and, spefically, of the overall reactions: IMP formation from PRib- PP, IMP → AMP and IMP → GMP, were followed by evaluating the incorporation curves of [ 14C]formate into hypoxanthine, adenine and guanine. Our results show that testosterone administration enhanced the incorporation rate and gave characteristic patterns: a diphasic cyclic oscillation of the Ade values in adult castrated rats, and single peaks having a specific shape in the other cases. The Gua/Ade labeling ratio was unchaned in castrated rats and increased in both groups during ther first 5 days after testosterone treatment, after which values even fell below normal; in most cases, values overlapped the pattern of the Gua/Ade molar ratio. The specific profile of the curves indicated that testosterone initially accelerated the turnover of guanylic acid and in the second phase re-established the normal behavior and ratio of AMP and GMP formation. These results indicate that the ‘inosinic branch point’ was subject to regulation by testosterone. The profiles of the incorporation curves and of the Gua/Ade ratio were indicative of a primary and secondary response to hormone action.