The Role of Bone-Derived Osteocalcin in Testicular Steroidogenesis: Contributing Factor to Male Fertility.

Osteocalcin (OCN), a protein predominantly produced by osteoblasts in bone, has emerged as a significant factor in bone metabolism and reproductive function. This article reviews the latest research on the role of OCN beyond its traditional functions in bone mineralisation, particularly its influence on testicular steroidogenesis and male fertility. The structure and modifications of OCN are elaborated upon, highlighting its uncarboxylated form (ucOCN), which is becoming increasingly recognised for its bioactive properties. The impact of OCN on bone quantity, quality and strength is summarised, emphasising its role as a regulator of bone metabolism. Furthermore, the influence of ucOCN on testicular steroidogenesis and the involvement of GPRC6A, a G protein-coupled receptor, in mediating these effects are also explored. Evidence suggests that ucOCN regulates testosterone synthesis and spermatogenesis, which indirectly have the potential to influence bone metabolism integrity. In conclusion, OCN, particularly in its uncarboxylated form, plays a crucial role in bone metabolism and male fertility by regulating testicular steroidogenesis, with GPRC6A mediating these effects, thereby linking bone health and reproductive functions.