Research output: Contribution to journal › Article › peer-review
Comparative study of the steroidogenic effects of human chorionic gonadotropin and thieno[2,3-d]pyrimidine-based allosteric agonist of luteinizing hormone receptor in young adult, aging and diabetic male rats. / Bakhtyukov, Andrey A.; Derkach, Kira V.; Gureev, Maxim A.; Dar’in, Dmitry V.; Sorokoumov, Viktor N.; Romanova, Irina V.; Morina, Irina Yu; Stepochkina, Anna M.; Shpakov, Alexander O.
In: International Journal of Molecular Sciences, Vol. 21, No. 20, 7493, 02.10.2020.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Comparative study of the steroidogenic effects of human chorionic gonadotropin and thieno[2,3-d]pyrimidine-based allosteric agonist of luteinizing hormone receptor in young adult, aging and diabetic male rats
AU - Bakhtyukov, Andrey A.
AU - Derkach, Kira V.
AU - Gureev, Maxim A.
AU - Dar’in, Dmitry V.
AU - Sorokoumov, Viktor N.
AU - Romanova, Irina V.
AU - Morina, Irina Yu
AU - Stepochkina, Anna M.
AU - Shpakov, Alexander O.
N1 - Bakhtyukov, A.A.; Derkach, K.V.; Gureev, M.A.; Dar’in, D.V.; Sorokoumov, V.N.; Romanova, I.V.; Morina, I.Y.; Stepochkina, A.M.; Shpakov, A.O. Comparative Study of the Steroidogenic Effects of Human Chorionic Gonadotropin and Thieno[2,3-D]pyrimidine-Based Allosteric Agonist of Luteinizing Hormone Receptor in Young Adult, Aging and Diabetic Male Rats. Int. J. Mol. Sci. 2020, 21, 7493.
PY - 2020/10/2
Y1 - 2020/10/2
N2 - 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.
AB - 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.
KW - Aging rats
KW - Diabetes mellitus
KW - Human chorionic gonadotropin
KW - Low-molecular-weight agonist
KW - Luteinizing hormone receptor
KW - Spermatogenesis
KW - Steroidogenesis
KW - Testes
UR - http://www.scopus.com/inward/record.url?scp=85092462739&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/1f4a890d-fa14-380c-a726-c896fdc7f30c/
U2 - 10.3390/ijms21207493
DO - 10.3390/ijms21207493
M3 - Article
C2 - 33050653
AN - SCOPUS:85092462739
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 20
M1 - 7493
ER -
ID: 70930497