Restoration of Bone Mass in Hpg Mouse by Preoptic Area Grafting

Hereditary hypogonadism in the hpg mouse, caused by a deletion mutation in the gonadotropin-releasing hormone (GnRH) gene, is associated with sterility, absent ovarian development, and undetectable circulating sex steroids. Eight-month-old female hpg mice had a significantly reduced bone mineral density (BMD) at the lumbar spine, femur, and tibia. In addition, the mice showed significant reductions in liver and kidney weight, with virtually nonexistent ovaries. Successfully transplanted hpg mice with preoptic area grafts contained GnRH-positive neurons, consistent with our previous experience, and the host median eminence was innervated by GnRH immunoreactive fibers. A return of reproductive function was evident from increased ovarian weight and vaginal cornification. Of note was that grafted hpg mice showed a complete reversal to baseline of their BMD measured at all three sites. This establishes that the low bone mass that occurs in old hpg mice can be fully and rapidly ameliorated by preoptic area grafting.