Testicular Function and Skeletal Alterations

Although testosterone is the major testicular factor that acts on the bone and allows for skeletal growth and bone mass accrual during development and puberty and maintain bone metabolism during adulthood, other functions of the Leydig cells are important in the testis-bone crosstalk. These cells in fact contribute to bone homeostasis also by producing the peptide hormone INSL3, which has an anabolic role acting on osteoblasts and osteocytes, and by expressing CYP2R1, an enzyme that converts the inactive cholecalciferol to 25-hydroxy vitamin D. All these functions are under the control of the pituitary LH hormone. Disturbed Leydig cell function, as observed in the primary, secondary, and subclinical hypogonadism, is associated with reduction of INSL3, 25-hydroxy vitamin D, and testosterone, therefore increasing the risk of osteoporosis. Leydig cell function is also regulated by the skeleton, as osteocalcin produced by osteoblasts acts in parallel to LH to stimulate testosterone and 25-hydroxy vitamin D production.