To correct androgen deficiency, it is necessary to develop a new luteinizing hormone receptor (LHR) agonists and evaluate their steroidogenic effect with different duration and routes of administration in comparison with human chorionic gonadotropin (hCG), the “gold” standard of steroidogenesis activators. The aim of the work was to study the effect of the allosteric LHR agonist 5-amino-N-tert-butyl-2-(methylsulfanyl)-4-(3-(nicotinamido)phenyl)thieno[2,3-d]-pyrimidine-6-carboxamide (TP03) after a single-dose and five-day intraperitoneal, subcutaneous and oral administration to male rats versus intraperitoneally or subcutaneously administered hCG. Testosterone levels and gene expression of LHR and steroidogenic enzymes were investigated. The doses of TP03 and hCG were preliminarily determined and subsequently used, causing 65−75% of the maximum steroidogenic effect. The TP03 (20 mg/kg) stimulated testosterone production more effectively with one- or five-day intraperitoneal administration than with subcutaneous and oral administration. Five-day intraperitoneal (but not subcutaneous) administration of TP03 increased the intra-testicular expression of the genes for LHR and the cholesterol-transporting protein StAR, which catalyzes the rate-limiting stage of steroidogenesis. The subcutaneous administration of hCG (20 IU/rat) was more effective than intraperitoneal administration, and significantly increased the expression of the 17β dehydrogenase gene, which catalyzes the synthesis of androstenedione. Both methods of hCG administration reduced the expression of the LHR gene. In contrast to hCG, after five days of administration, the steroidogenic effect of TP03 persisted. It was concluded that the steroidogenic effect of TP03 is most pronounced with intraperitoneal administration, and in the case of hCG, with subcutaneous administration, which is due to differential effects of these drugs on the expression of steroidogenic enzymes.
Translated title of the contribution A COMPARATIVE STUDY OF THE STEROIDOGENIC EFFECT OF 5-AMINO-N-TERT-BUTYL-2-(METHYLTHIO)- 4-(3-(NICOTINAMIDO)PHENYL)THIENO[2,3-D]-PYRIMIDINE- 6-CARBOXAMIDE AND CHORIONIC GONADOTROPIN WITH DIFFERENT METHODS OF ADMINISTRATION TO MALE RATS
Original languageRussian
Pages (from-to)51-60
Number of pages10
JournalЖУРНАЛ ЭВОЛЮЦИОННОЙ БИОХИМИИ И ФИЗИОЛОГИИ
Volume58
Issue number1
DOIs
StatePublished - Jan 2022

    Research areas

  • TESTES, STEROIDOGENESIS, THIENOPYRIMIDINE, CHORIONIC GONADOTROPIN, INTRAPERITONEAL ADMINISTRATION, SUBCUTANEOUS ADMINISTRATION, TESTOSTERONE

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