Department of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Damascus, Syrian Arab Republic.
Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padua, Italy.
J Endocrinol Invest. 2022 Sep;45(9):1673-1682. doi: 10.1007/s40618-022-01803-9. Epub 2022 Apr 28.
Undercarboxylated-Osteocalcin (ucOCN), acting on its putative receptor GPRC6A, was shown to stimulate testosterone (T) production by Leydig cells in rodents, in parallel with the hypothalamus-pituitary-gonadal axis (HPG) mediated by luteinizing hormone (LH). The aim of this cross-sectional study was to evaluate the association among serum ucOCN, rs2247911 polymorphism of GPRC6A gene and the endocrine/semen pattern in a cohort of infertile males, possibly identifying an involvement of the ucOCN-GPRC6A axis on testis function.
190 males, including 74 oligozoospermic subjects, 58 azoosperminc patients and 58 normozoospermic controls, were prospectively recruited at the Orient Hospital for Infertility, Assisted Reproduction and Genetics in Syria (Study N. 18FP), from July 2018 to June 2020. Outpatient evaluation included the clinical history, anthropometrics and a fasting blood sampling for hormonals, serum OCN (both carboxylated and undercarboxylated), glycemic and lipid profile and screening for rs2247911 GPRC6A gene polymorphism.
Higher serum ucOCN associated with higher T and HDL-cholesterol (respectively: r = 0.309, P < 0.001 and r = 0.248, P = 0.001), and with lower FSH (r = - 0.327, P < 0.001) and LDL-cholesterol (r = - 0.171; P = 0.018). Patients bearing the GG genotype of rs2247911 had higher sperm count compared to GA genotype (P = 0.043) and, compared to both AG and AA genotypes, had higher serum T (P = 0.004, P = 0.001) and lower triglycerides levels (P = 0.002, P < 0.001). Upon normalization for LH levels and body mass index, rs2274911 and ucOCN were significantly associated with higher serum T at linear stepwise regression analysis (P = 0.013, P = 0.007).
Our data suggest the involvement of ucOCN-GPRC6A axis in the regulation of T production by the testis, subsidiary to HPG.
已证实，去羧化骨钙素（ucOCN）通过其假定受体 GPRC6A 作用，可与黄体生成素（LH）介导的下丘脑-垂体-性腺轴（HPG）平行刺激睾丸间质细胞产生睾酮（T）。本横断面研究旨在评估血清 ucOCN、GPRC6A 基因 rs2247911 多态性与不育男性内分泌/精液模式之间的关联，以期确定 ucOCN-GPRC6A 轴对睾丸功能的影响。
2018 年 7 月至 2020 年 6 月，叙利亚东方不孕不育、辅助生殖和遗传学医院（研究编号 18FP）前瞻性招募了 190 名男性，包括 74 名少精子症患者、58 名无精子症患者和 58 名正常精子症患者。门诊评估包括临床病史、人体测量学以及空腹血液取样，用于检测激素、血清 OCN（羧化和去羧化）、血糖和血脂谱以及 rs2247911 GPRC6A 基因多态性。
较高的血清 ucOCN 与较高的 T 和高密度脂蛋白胆固醇相关（分别为：r=0.309，P<0.001 和 r=0.248，P=0.001），与较低的 FSH（r=-0.327，P<0.001）和 LDL 胆固醇相关（r=-0.171；P=0.018）。与 GA 基因型相比，rs2247911 的 GG 基因型患者的精子计数更高（P=0.043），与 AG 和 AA 基因型相比，血清 T 更高（P=0.004，P=0.001），甘油三酯水平更低（P=0.002，P<0.001）。在校正 LH 水平和体重指数后，rs2274911 和 ucOCN 在逐步线性回归分析中与血清 T 升高显著相关（P=0.013，P=0.007）。
我们的数据表明，ucOCN-GPRC6A 轴参与了 HPG 对睾丸 T 产生的调节。
