Ранние стероидогенные эффекты гонадотропина и низкомолекулярного агониста рецептора лютеинизирующего гормона при введении их субмаксимальных доз самцам крыс

Abstract

The receptors of luteinizing hormone (LH) play a key role in the regulation of testicular steroidogenesis. They can be activated by gonadotropins, LH and human chorionic gonadotropin (hCG), and by the low-molecular-weight agonists, including the derivatives of thieno[2,3-d]pyrimidines, which bind to an allosteric site located in the transmembrane channel of LH receptor. The differences in the steroidogenic effects of gonadotropins and thieno[2,3-d]pyrimidines in the in vitro experiments and in a long-term administration to male rats were previously identified, but their early steroidogenic effects in the testes when administered at submaximal doses, have not been studied . The aim of the work was to study the effect of a single administration of hCG and TP03, a thieno[2,3-d]pyrimidine derivative, in submaximal doses on testosterone (T) plasma levels and on the expression of steroidogenic protein genes of, as well as the pattern of steroid hormones, the precursors of T, in the testes for 5 hours after the treatment of male rats. We demonstrate that TP03 (15 mg/kg) and hCG (50 IU/rat) 30 minutes after their administration to rats cause an increase in the intratesticular levels of T and its precursors, such as 17-hydroxyprogesterone and androstenedione, and also reduce the level of pregnenolone, which indicates its expenditure for progesterone synthesis. The gene expression of steroidogenic proteins significantly changed 3 hours after drug administration. The administration of TP03 and hCG led to an increase in the expression of the Star and Cyp17a1 genes encoding the transport protein StAR and the cytochrome P450-17α, the key components of the steroidogenesis system. At the same time, the difference between the expressions of the Hsd17b gene encoding the dehydrogenase HSD17β, which were higher in the hCG-treated group as compared to the TP03-treated group, is shown. An increase in the plasma T levels one and three hours after treatment of rats with hCG was higher than in the TP03-treated group, but after 5 hours the T levels in both groups of rats were comparable, which was due to the weakening of the steroidogenic effect of hCG while maintaining the corresponding effect of TP03. Thus, despite the similarity of the early steroidogenic effects of TP03 and hCG used at the submaximal doses, even in the first hours after their administration to rats, the peculiarities of their effect on testicular steroidogenesis begin to appear, which, after a long-term administration, lead to significant differences in their steroidogenic activity.