| Autor: |
Bakhtyukov AA; Department of Biochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 Saint Petersburg, Russia., Derkach KV; Department of Biochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 Saint Petersburg, Russia., Gureev MA; Department of Bioinformatics and Medicinal Chemistry, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia., Dar'in DV; Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University, 198504 Saint Petersburg, Russia., Sorokoumov VN; Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University, 198504 Saint Petersburg, Russia., Romanova IV; Department of Biochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 Saint Petersburg, Russia., Morina IY; Department of Biochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 Saint Petersburg, Russia., Stepochkina AM; Department of Biochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 Saint Petersburg, Russia., Shpakov AO; Department of Biochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 Saint Petersburg, Russia. |
| Abstrakt: |
Low-molecular-weight agonists of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LHCGR), which interact with LHCGR transmembrane allosteric site and, in comparison with gonadotropins, more selectively activate intracellular effectors, are currently being developed. Meanwhile, their effects on testicular steroidogenesis have not been studied. The purpose of this work is to perform a comparative study of the effects of 5-amino- N - tert -butyl-4-(3-(1-methylpyrazole-4-carboxamido)phenyl)-2-(methylthio)thieno[2,3- d ] pyrimidine-6-carboxamide (TP4/2), a LHCGR allosteric agonist developed by us, and hCG on adenylyl cyclase activity in rat testicular membranes, testosterone levels, testicular steroidogenesis and spermatogenesis in young (four-month-old), aging (18-month-old) and diabetic male Wistar rats. Type 1 diabetes was caused by a single streptozotocin (50 mg/kg) injection. TP4/2 (20 mg/kg/day) and hCG (20 IU/rat/day) were administered for 5 days. TP4/2 was less effective in adenylyl cyclase stimulation and ability to activate steroidogenesis when administered once into rats. On the 3rd-5th day, TP4/2 and hCG steroidogenic effects in young adult, aging and diabetic rats were comparable. Unlike hCG, TP4/2 did not inhibit LHCGR gene expression and did not hyperstimulate the testicular steroidogenesis system, moderately increasing steroidogenic proteins gene expression and testosterone production. In aging and diabetic testes, TP4/2 improved spermatogenesis. Thus, during five-day administration, TP4/2 steadily stimulates testicular steroidogenesis, and can be used to prevent androgen deficiency in aging and diabetes. |
