Conservation of Steroidogenic Effect of the Low-Molecular-Weight Agonist of Luteinizing Hormone Receptor in the Course of Its Long-Term Administration to Male Rats

• Published in: Doklady. Biochemistry and biophysics 2019-05, Vol.484 (1), p.78-81
• Main Authors: Bakhtyukov, A. A., Derkach, K. V., Dar’in, D. V., Shpakov, A. O.
• Format: Article
• Language: English
• Subjects: 3-Hydroxysteroid Dehydrogenases - biosynthesis; Agonists; Animals; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Chorionic gonadotropin; Chorionic Gonadotropin - pharmacology; Cytochrome P-450 Enzyme System - biosynthesis; Gonadotropins; Leydig cells; Leydig Cells - cytology; Leydig Cells - metabolism; Life Sciences; Luteinizing hormone; Male; Molecular Biology; Pituitary (anterior); Rats; Receptors, LH - agonists; Rodents; Testosterone; Testosterone - biosynthesis; Thienopyridines - pharmacology
• ISSN: 1607-6729; 1608-3091
• DOI: 10.1134/S1607672919010216

—It was shown that the thienopyrimidine derivative TP03, a low-molecular-weight agonist of the luteinizing hormone receptor (LHR), during the treatment of male rats for 7 days steadily increased the production of testosterone (T), whose elevated level was retained for 7 days, and increased the expression of the gene for LHR, which indicates the maintenance of the sensitivity of Leydig cells to gonadotropins. At the same time, the steroidogenic effect of human chorionic gonadotropin (hCG), which significantly increased the T level on the first day of administration, was further weakened, which was accompanied by a decrease in the expression of the gene for LHR in the testes, indicating the development of resistance of Leydig cells to hCG. Along with this, in the case of hCG administration, a compensatory increase in the expression of genes of the steroidogenic enzymes, such as cytochrome P450 scc and dehydrogenase 3β-HSD, was shown in the testes, while in the case of TP03 administration this effect was absent.