Effect of testosterone on purine nucleotide metabolism in rat liver.

In previous studies, we found that castration induced interesting morphological and biochemical changes in rat liver. For the present study, we have examined the effects of testosterone on the kinetics of purine nucleotide metabolism with the aim of determining the steps affected by testosterone deficiency. A biomathematical model of purine nucleotide metabolism was used to analyze the many reactions involved. The model simplifies purine nucleotide metabolism to four main steps: 1) de novo synthesis from PRPP to IMP; 2) the inosinic branch point from IMP to GMP or AMP; 3) catabolism of IMP, AMP and GMP to uric acid; 4) RNA and DNA formation from AMP and GMP. We evaluated rate constants from each step from variations in specific radioactivity of metabolites labelled with (14)C-formate, a precursor of de novo synthesis. The model was applied to the liver of normal and castrated rats before and after testosterone treatment. All four steps were slowed after castration, and were not completely restored by androgen administration. The model can give a clear representation of the kinetics of the reactions involved in the liver nucleotide metabolism investigated here, and we propose that a similar approach could be useful whenever a quantitative evaluation of the results obtained in vivo after administration of labelled precursors is required.

The hormonal regulation of purine nucleotide turnover. Influence of testosterone in rat liver.

An influence of testosterone on de novo purine nucleotide synthesis has been demonstrated in rat liver of adult and prepubertal castrated rats, showing that the action of the hormone is not limited to sexual organs. Castration accelerated the turnover of purine nucleotides in adults rats and reduced it in prepubertal castrated rats. Administration of testosterone tended to restore normality in both cases with opposite mechanisms, lowering the reaction rates in the first group, enhancing them in the second one. An action of the hormone on the inosinic branch-point and specifically on GMP synthesis, was evident, which was again different according to the age of the animal. The observed changes in purine nucleotide metabolism could be responsible for variations in RNA and DNA metabolism, in cellular size and number--which probably occur in the liver--after orchiectomy and following androgen administration.

Influence of testosterone on purine nucleotide turnover in rat kidney.

The influence of testosterone on purine nucleotide metabolism in rat kidney has been investigated in adult and in prepubertal castrated rats. Results have been evaluated through biomathematical model. Castration enhanced the turnover of purine nucleotides in adult rats and reduced it in young castrated rats. Treatment with testosterone in the castrated rats further enhanced nucleotide turnover both in the adult rats and also in the second group, with an oscillatory profile. A clear effect on the inosinic branch point was demonstrated, and specifically on GMP formation, which was opposite according to the age of the animal. The different behavior in the two groups after castration was partially ascribed to the action of other hormones in the absence of testosterone. The observed changes show that the action of the hormone is not limited to sexual organs; they might be at the basis of variations in cellular size and number which probably occur in the kidney after orchiectomy and following androgen administration.

Growth of fetuses of diabetic mothers.

Longitudinal ultrasonographic examinations, with measurements of fetal biparietal diameter and abdominal circumference, were performed in 85 diabetic pregnant women submitted to different treatment protocols. Curves of fetal growth parameters were obtained for each group of patients and for a control group of normal fetuses, applying the function y = k(MA)2.e-a(MA) to the ultrasonographic data. With the use of this function it was possible to demonstrate that there are no significant differences in the pattern of fetal growth when a strict metabolic control is obtained in diabetic pregnant women.