Endocrine Abstracts

Purpose: Undercarboxylated-Osteocalcin (ucOCN), acting on its putative receptor GPRC6A, was shown to stimulate of 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 is to evaluate the association among serum ucOCN, rs2247911 polymorphism of GPRC6A gene and the endocrine/reproductive pattern in a cohort of infertile males, possibly identifying an involvement of the ucOCN-GPRC6A axis on testis function.

Methods: 172 males, including 74 oligozoospermic, 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 and 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.

Results: 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 coung compared to GA genotype (P=0.043) and, compared to both AG and AA genotypes, 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).

Conclusions: Our data suggest the involvement of ucOCN-GPRC6A axis in the regulation of T production by the testis complementary to HPG.