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.

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.

— A characteristic feature of type 1 diabetes mellitus (DM1) in humans and experimental animals is an androgen deficiency, which is usually compensated by using the gonadotropin preparations...

Hashimoto thyroiditis is the most common thyroid disease. This form of pathology has a diverse clinical picture, including neuropsychiatric disorders. There are frequent cases of comorbidity of autoimmune thyroiditis and psychiatric forms of pathology, along with such a nosological entity as Hashimotos encephalopathy (aka: Steroid-responsive encephalopathy of autoimmune thyroiditis), characterized by an increased level of antithyroid autoantibodies and various mental disorders, with still unclear pathogenesis. The question arises, how to regard patients with psychiatric disorders and Hashimoto thyroiditis either as patients having autoimmune thyroiditis, comorbid with psychiatric forms of pathology, or as patients with Hashimotos encephalopathy? We studied groups of patients with autoimmune thyroiditis free from any psychiatric disorders, autoimmune thyroiditis comorbid with psychiatric forms of pathology, and a group of healthy donors similar as regards to their age and sex. We also studied medical history, clinical manifestations of the disease, instrumental data and the serum levels of thyrotropin, thyroid hormones, various antithyroid autoantibodies, and prolactin. We analyzed the correlation of laboratory and instrumental parameters and clinical data in all groups of patients. Therewas a significant relationship (p 0,05) between various psychiatric symptoms and a decreased level of free thyroxine, an increased level of thyroid stimulating hormone (TSH), an increased level of prolactin and an increased volume of a thyroid gland. Asignificant relationship (p 0,05) was also found between various symptoms of hypothyroidism and a decreased level of free triiodothyronine (FT3), an increased level of antibodies to thyroglobulin (anti-TG Ab), and an increased level of antibodies to thyroid peroxidase (anti-TPO Ab).

Восстановление функций мужской репродуктивной системы при сахарном диабете 2-го типа (СД2) представляет собой одну из актуальных проблем современной эндокринологии. Для этого могут быть использованы как препараты, улучшающие глюкозный гомеостаз и инсулиновую чувствительность, в первую очередь метформин, так и активаторы рецептора лютеинизирующего гормона (ЛГР) – хорионический гонадотропин человека (ХГЧ) и низкомолекулярные аллостерические агонисты ЛГР. Целью исследования было изучить влияние метформиновой терапии (4 нед., 120 мг/кг/сутки) на стимулирующие стероидогенез и сперматогенез эффекты, вызываемые пятидневным введением самцам крыс Вистар с СД2 5-амино-N-трет-бутил-2-(метилсульфанил)-4-(3-(никотинамидо)фенил)тиено[2,3-d]пиримидин-6-карбоксамида (ТП03), аллостерического ЛГР-агониста (15 мг/кг/сутки), и ХГЧ (20 МЕ/крысу/сутки). СД2 вызывали высокожировой диетой и инъекцией низкой дозы стрептозотоцина (25 мг/кг). Лечение метформином частично восстанавливало уровни тестостерона и нормализовало сперматогенез у крыс с СД2...