Bone phenotypes in response to gonadotropin misexpression: the role for gonadotropins in postmenopausal osteoporosis

Jason P Mansell

Department of Oral and Dental Sciences, Division of Oral Medicine, University of Bristol Dental School, Lower Maudlin Street, Bristol, BS1 2LY, UK

Abstract: Scant attention has been paid to the potential role of gonadotropins in bone tissue homeostasis. The focus on estrogen and estrogen replacement therapy for osteoporosis as far back as the 1940’s may account for the paucity of gonadotropin studies in bone biology. It is conceivable that prevailing dogma may have subconsciously steered us away from addressing whether gonadotropins have a place in skeletal physiology. However an examination of bone tissue catabolism in ovariectomized (OVX) and luteinizing hormone-releasing hormone (LHRH) agonist (Zoladex^®)-treated rats generated some interesting and conflicting data; Zoladex-treated rats, unlike the OVX group, failed to exhibit increased bone collagen catabolism despite clear evidence for estrogen deficiency. The findings, although controversial, supported the possibility that elevated gonadotropins in the OVX model were in some way accountable for increased bone catabolism. In response to these initial findings further studies were performed to determine if altered LH status may in some way impact on the skeleton To this end an investigation of bone mass and histomorphometry were conducted in LH receptor nullizygous mice and human chorionic gonadotropin (hCG) overexpressing mice. There were clear phenotypic differences; the LH receptor knockout mice displayed reduced bone mass whereas the hCG overexpressing animals had stark increases in bone mass. Much more recently the team of the Mount Sinai Bone Program have made a significant discovery that bone-resorbing osteoclasts express receptors for follicle-stimulating hormone (FSH) and that mice nullizygous for FSH receptor are resistant to bone loss despite severe estrogen deficiency. Details of these fascinating models will be presented together with additional findings that give credence for exploring gonadotropin action on the skeleton as we enter the twilight of this Decade of the Bone and Joint.

Keywords: gonadotropins, bone, osteoblasts, osteoclasts, follicle-stimulating hormone, luteinizing hormone