Next Article in Journal
Regulation and Function of Laminin A5 during Mouse and Human Decidualization
Next Article in Special Issue
Metformin Repurposing for Parkinson Disease Therapy: Opportunities and Challenges
Previous Article in Journal
Modulation of Insulin Resistance, Dyslipidemia and Serum Metabolome in iNOS Knockout Mice following Treatment with Nitrite, Metformin, Pioglitazone, and a Combination of Ampicillin and Neomycin
Previous Article in Special Issue
Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area
Article

The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis

1
Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 St. Petersburg, Russia
2
Institute of Chemistry, Saint Petersburg State University, 198504 St. Petersburg, Russia
*
Author to whom correspondence should be addressed.
Academic Editor: Jolanta Weaver
Int. J. Mol. Sci. 2022, 23(1), 198; https://doi.org/10.3390/ijms23010198
Received: 30 November 2021 / Revised: 18 December 2021 / Accepted: 21 December 2021 / Published: 24 December 2021
(This article belongs to the Special Issue Metformin: The Scope for New Applications)
In men with type 2 diabetes mellitus (T2DM), steroidogenesis and spermatogenesis are impaired. Metformin and the agonists of luteinizing hormone/human chorionic gonadotropin(hCG)-receptor (LH/hCG-R) (hCG, low-molecular-weight allosteric LH/hCG-R-agonists) can be used to restore them. The aim was to study effectiveness of separate and combined administration of metformin, hCG and 5-amino-N-tert-butyl-2-(methylsulfanyl)-4-(3-(nicotinamido)phenyl)thieno[2,3-d]pyrimidine-6-carboxamide (TP3) on steroidogenesis and spermatogenesis in male rats with T2DM. hCG (15 IU/rat/day) and TP3 (15 mg/kg/day) were injected in the last five days of five-week metformin treatment (120 mg/kg/day). Metformin improved testicular steroidogenesis and spermatogenesis and restored LH/hCG-R-expression. Compared to control, in T2DM, hCG stimulated steroidogenesis and StAR-gene expression less effectively and, after five-day administration, reduced LH/hCG-R-expression, while TP3 effects changed weaker. In co-administration of metformin and LH/hCG-R-agonists, on the first day, stimulating effects of LH/hCG-R-agonists on testosterone levels and hCG-stimulated expression of StAR- and CYP17A1-genes were increased, but on the 3–5th day, they disappeared. This was due to reduced LH/hCG-R-gene expression and increased aromatase-catalyzed estradiol production. With co-administration, LH/hCG-R-agonists did not contribute to improving spermatogenesis, induced by metformin. Thus, in T2DM, metformin and LH/hCG-R-agonists restore steroidogenesis and spermatogenesis, with metformin being more effective in restoring spermatogenesis, and their co-administration improves LH/hCG-R-agonist-stimulating testicular steroidogenesis in acute but not chronic administration. View Full-Text
Keywords: metformin; male reproduction; type 2 diabetes mellitus; allosteric agonist; luteinizing hormone receptor; chorionic gonadotropin; testicular steroidogenesis; spermatogenesis metformin; male reproduction; type 2 diabetes mellitus; allosteric agonist; luteinizing hormone receptor; chorionic gonadotropin; testicular steroidogenesis; spermatogenesis
Show Figures

Figure 1

MDPI and ACS Style

Bakhtyukov, A.A.; Derkach, K.V.; Sorokoumov, V.N.; Stepochkina, A.M.; Romanova, I.V.; Morina, I.Y.; Zakharova, I.O.; Bayunova, L.V.; Shpakov, A.O. The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis. Int. J. Mol. Sci. 2022, 23, 198. https://doi.org/10.3390/ijms23010198

AMA Style

Bakhtyukov AA, Derkach KV, Sorokoumov VN, Stepochkina AM, Romanova IV, Morina IY, Zakharova IO, Bayunova LV, Shpakov AO. The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis. International Journal of Molecular Sciences. 2022; 23(1):198. https://doi.org/10.3390/ijms23010198

Chicago/Turabian Style

Bakhtyukov, Andrey A., Kira V. Derkach, Viktor N. Sorokoumov, Anna M. Stepochkina, Irina V. Romanova, Irina Y. Morina, Irina O. Zakharova, Liubov V. Bayunova, and Alexander O. Shpakov. 2022. "The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis" International Journal of Molecular Sciences 23, no. 1: 198. https://doi.org/10.3390/ijms23010198

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop