Bakhtyukov A A, Derkach K V, Dar'in D V, Shpakov A O
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia.
St. Petersburg State University, St. Petersburg, Russia.
Dokl Biochem Biophys. 2019 May;484(1):78-81. doi: 10.1134/S1607672919010216. Epub 2019 Apr 22.
Abstract-It was shown that the thienopyrimidine derivative TP03, a low-molecular-weight agonist of the luteinizing hormone receptor (LHR), during the treatment of male rats for 7 days steadily increased the production of testosterone (T), whose elevated level was retained for 7 days, and increased the expression of the gene for LHR, which indicates the maintenance of the sensitivity of Leydig cells to gonadotropins. At the same time, the steroidogenic effect of human chorionic gonadotropin (hCG), which significantly increased the T level on the first day of administration, was further weakened, which was accompanied by a decrease in the expression of the gene for LHR in the testes, indicating the development of resistance of Leydig cells to hCG. Along with this, in the case of hCG administration, a compensatory increase in the expression of genes of the steroidogenic enzymes, such as cytochrome P450 and dehydrogenase 3β-HSD, was shown in the testes, while in the case of TP03 administration this effect was absent.
研究表明，噻吩并嘧啶衍生物TP03是促黄体生成素受体（LHR）的低分子量激动剂，在对雄性大鼠进行7天治疗期间，可使睾酮（T）的分泌持续稳定增加，且T水平升高可维持7天，同时可增加LHR基因的表达，这表明睾丸间质细胞对促性腺激素的敏感性得以维持。与此同时，人绒毛膜促性腺激素（hCG）给药第一天可显著提高T水平，但其类固醇生成作用在后续进一步减弱，同时睾丸中LHR基因的表达下降，这表明睾丸间质细胞对hCG产生了抗性。此外，在给予hCG的情况下，睾丸中细胞色素P450和3β-羟基类固醇脱氢酶等类固醇生成酶基因的表达出现代偿性增加，而给予TP03则未出现此效应。
