RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function

RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function

Purpose 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 s...

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Published in:Journal of endocrinological investigation Vol. 45; no. 9; pp. 1673 - 1682
Main Authors: Jawich, K., Rocca, M. Santa, Al Fahoum, S., Alhalabi, M., Di Nisio, A., Foresta, C., Ferlin, A., De Toni, L.
Format: Journal Article
Language:English
Published: Cham Springer International Publishing 01-09-2022
Springer Nature B.V
Subjects:
Body mass index
Cholesterol
Endocrinology
Follicle-stimulating hormone
Gene polymorphism
High density lipoprotein
Hypothalamus
Infertility
Internal Medicine
Leydig cells
Low density lipoprotein
Luteinizing hormone
Medicine
Medicine & Public Health
Metabolic Diseases
Original Article
Osteocalcin
Patients
Pituitary
Polymorphism
Testosterone
Triglycerides
GPRC6A
Testosterone
Osteocalcin
Bone
Male infertility
Leydig cells
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Summary:Purpose 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. Methods 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. 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 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). Conclusions Our data suggest the involvement of ucOCN-GPRC6A axis in the regulation of T production by the testis, subsidiary to HPG.
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ISSN:1720-8386
0391-4097
1720-8386
DOI:10.1007/s40618-022-01803-9