Male pubertal development: role of androgen therapy on bone mass and body composition.

Puberty is the developmental period during which rapid somatic changes and attainment of reproductive capacity take place. The sine qua non event for the onset of puberty is the increase in pulsatile GnRH release from GnRH neurons. GnRH neurons originate in the nasal placode and migrate, from the nasal compartment through the basal forebrain, before they attain their positions in the hypothalamus. Failure of GnRH neurons to migrate, mainly due to genetic alterations, leads to a clinical condition defined congenital hypogonadotropic hypogonadism. Other important factors demonstrated a permissive role for GnRH secretion at time of puberty, such as the kisspeptin G-protein-coupled receptor 54 (GPR54, now called KISS-1R) and its ligand, as well as neurokinin B (NKB) and the neurokinin 3 (NK3) receptor. Kisspeptin and neurokinin B colocalized in a subset of hypothalamic neurons that regulate GnRH secretion by GnRH neurons. Indeed, loss of function mutations in the above-mentioned and other genes result in hypogonadotrophic hypogonadism with absence of pubertal development. In males, pubertal increase of androgens levels seems to be required for the attainment of a normal bone density and male-specific body composition. However, also genetic variants of genes involved in bone metabolism as well as in osteoblast/osteoclast activation are associated to bone mineral density.