Comparative analysis of the steroidogenic effects of thienopyrimidine derivatives with the activity of partial agonists of the luteninizing hormone receptor DOI
К. В. Деркач, V. N. Sorokoumov, А. О. Шпаков

et al.

Reviews on Clinical Pharmacology and Drug Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Background: Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) preparations are widely used in medicine to correct reproductive disorders, but characterized by many side effects. In this regard, low-molecular-weight allosteric agonists of the LH receptor (LHR) being developed, most active which thieno[2,3-d]-pyrimidine derivatives (TPs). Aim: To study stimulating effects compound TP03, developed us, on activity membrane-bound adenylate cyclase (AC) vitro testicular ovarian steroidogenesis vivo comparison with those Org43553, “gold” standard LHR agonists. Materials methods: The TP03 Org43553 (10-8–10-3 M) basal hCG-stimulated (10-9 AC membrane fractions isolated from rat testes ovaries were assessed using [α-32P]-ATP. (in two doses – 10 20 mg/kg, i.p.) blood testosterone levels male rats progesterone immature female pre-stimulated Follimag® vivo, as well effect co-administration or (10 hCG IU/rat, s.c.) rats. Testosterone determined enzyme immunoassay. Results: Compound was comparable its ability stimulate membranes. When administered rats, dose-dependently stimulated production, when it increased their levels, not inferior these parameters. relatively low together additivity observed, more pronounced than case a combination hCG. Conclusions: we is along this, demonstrates hCG, indicates prospects for use increase effectiveness therapy.

Language: Английский

Effect of Intranasally Administered Insulin on Metabolic Parameters and Inflammation Factors in Control and Diabetic Rats under Conditions of Cerebral Ischemia and Reperfusion DOI
И. И. Зорина, A. S. Pechalnova,

E. E. Chernenko

et al.

Российский физиологический журнал им  И  М  Сеченова, Journal Year: 2024, Volume and Issue: 110(6), P. 976 - 993

Published: Oct. 20, 2024

The search for natural biologically active substances that have a neuroprotective effect on cerebral ischemia-reperfusion is one of the urgent problems modern neuroscience and medicine. Intranasally administered insulin (IAI) has pronounced restorative various neurodegenerative diseases, but mechanisms its action therapeutic effects in ischemia not been studied well, including type 2 diabetes mellitus (DM2), which increases risk cerebrovascular dysfunction. aim work was to study IAI metabolic parameters inflammatory factors male rats with DM2 subjected two-vessel prolonged forebrain reperfusion, comparison non-diabetic animals. A long-term high-fat diet an injection low dose streptozotocin (25 mg/kg) used induce DM2, model global induced by occlusion both common carotids reperfusion (IR) 7 days ischemia. Two hours after end ischemia, were treated at 0.5 or 2.0 IU/rat, drug same doses daily subsequent days. It found prevents body weight loss nondiabetic diabetic underwent IR, also total cholesterol level proportion epididymal fat without IR. In explored reduces postprandial glucose content blood, indicates improvement tolerance, levels blood – C-reactive protein (at IU/rat/day) tumor necrosis factor-α (in IU/rat/day), reveals anti-inflammatory potential. Thus, course treatment induction followed leads weakens reactions may be demand correction ischemic stroke patients DM2.

Language: Английский

Citations

0
Sexual Dimorphism in Impairment of Acetylcholine-Mediated Vasorelaxation in Zucker Diabetic Fatty (ZDF) Rat Aorta: A Monogenic Model of Obesity-Induced Type 2 Diabetes DOI Open Access

Rifat Ara Islam,

Xiaoyuan Han, Sonali Shaligram

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11328 - 11328

Published: Oct. 21, 2024

Several reports, including our previous studies, indicate that hyperglycemia and diabetes mellitus exert differential effects on vascular function in males females. This study examines sex differences the of type 2 (T2D) an established monogenic model obesity-induced T2D, Zucker Diabetic Fatty (ZDF) rats. Acetylcholine (ACh) responses were assessed phenylephrine pre-contracted rings before after apocynin, a NADPH oxidase (NOX) inhibitor. The mRNA expressions aortic endothelial NOS (eNOS), key NOX isoforms also measured. We demonstrated following: (1) had contrasting vasorelaxation ZDF rats, impairing relaxation to ACh females while enhancing it male rats; (2) inhibition NOX, major source superoxide vasculature, restored female (3) eNOS NOX4 elevated (but not male) rat aortas compared their respective leans. highlights sexual dimorphism ACh-mediated aorta suggesting may play role impaired observed

Language: Английский

Citations

0
Leptin fragment modulates the stimulatory effects of chorionic gonadotropin on testicular steroidogenesis in a model of diet-induced obesity in rats DOI
A. A. Bakhtyukov, I. A. Lebedev, I. Yu. Morina

et al.

Журнал эволюционной биохимии и физиологии, Journal Year: 2024, Volume and Issue: 60(3), P. 223 - 233

Published: Nov. 16, 2024

Language: Английский

Citations

0
Multiple mechanisms of allosteric regulation of the luteninizing hormone receptor DOI

A. O. Shpakov,

К. В. Деркач

Успехи физиологических наук, Journal Year: 2024, Volume and Issue: 55(4), P. 45 - 74

Published: Dec. 8, 2024

The regulatory effects of luteinizing hormone (LH) and chorionic gonadotropin (CG) are realized through the activation G-protein coupled LH/CG receptor (LH/CG-R). result this is various types G proteins, which leads to stimulation (Gs) or inhibition (Gi) cAMP-dependent pathway calcium signaling (Gq/11, Gi), recruitment β-arrestins, prevent protein internalization downregulation, but can also activate mitogen-activated kinase cascade. Despite a certain similarity in LH CG, there differences between them both efficiency pattern regulation LH/CG-R. This consequence affinity CG orthosteric site receptor, as well at level allosteric due presence C-terminal extension β-subunit including sites for O-glycosylation, variability N-glycosylation α- β-subunits gonadotropins. Moreover, number N-glycans, degree their branching charge differ, different intracellular cascades, affecting physiological response reproductive system Of great importance formation homodi(oligo)meric complexes LH/CG-R its heterocomplexes with follicle-stimulating where protomers allosterically influence bias signal transduction. Taking into account large LH/CG-R, development low-molecular regulators underway, agonists based on thieno[2,3-d]-pyrimidine peptides derived from cytoplasmic loops These become prototypes drugs correcting functions system. review devoted analysis data similarities gonadotropins activity, role mechanisms this, prospects creating

Language: Английский

Citations

0
Comparative analysis of the steroidogenic effects of thienopyrimidine derivatives with the activity of partial agonists of the luteninizing hormone receptor DOI
К. В. Деркач, V. N. Sorokoumov, А. О. Шпаков

et al.

Reviews on Clinical Pharmacology and Drug Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Background: Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) preparations are widely used in medicine to correct reproductive disorders, but characterized by many side effects. In this regard, low-molecular-weight allosteric agonists of the LH receptor (LHR) being developed, most active which thieno[2,3-d]-pyrimidine derivatives (TPs). Aim: To study stimulating effects compound TP03, developed us, on activity membrane-bound adenylate cyclase (AC) vitro testicular ovarian steroidogenesis vivo comparison with those Org43553, “gold” standard LHR agonists. Materials methods: The TP03 Org43553 (10-8–10-3 M) basal hCG-stimulated (10-9 AC membrane fractions isolated from rat testes ovaries were assessed using [α-32P]-ATP. (in two doses – 10 20 mg/kg, i.p.) blood testosterone levels male rats progesterone immature female pre-stimulated Follimag® vivo, as well effect co-administration or (10 hCG IU/rat, s.c.) rats. Testosterone determined enzyme immunoassay. Results: Compound was comparable its ability stimulate membranes. When administered rats, dose-dependently stimulated production, when it increased their levels, not inferior these parameters. relatively low together additivity observed, more pronounced than case a combination hCG. Conclusions: we is along this, demonstrates hCG, indicates prospects for use increase effectiveness therapy.

Language: Английский

Citations

0