title: Perinatal testosterone surge is required for normal adult bone size but not for normal bone remodeling.
abstract: Although testosterone (T) has striking effects on mature skeletal size and structure, it is not clear whether this depends exclusively on adult circulating levels of T or whether additional early-life factors also play a role. We have compared the androgen-deficient hypogonadal (hpg) mutant mouse with intact, orchidectomized, and T-treated non-hpg mice to determine relative contributions of adult and perinatal T to bone growth and development. At 3 wk of age, although trabecular and cortical bone structure was normal, bone turnover was significantly altered in hpg male mice; osteoid volume (OV/BV) and osteoblast surface (ObS/BS) were significantly lower and osteoclast surface (OcS/BS) significantly higher in hpg mice compared with age-matched non-hpg mice, pointing to a role for the perinatal T surge in determining bone turnover levels before sexual maturity. At 9 wk of age, the hpg bone phenotype mimicked closely that of age-matched non-hpg mice that had been orchidectomized at 3 wk of age, including low trabecular bone mass and high bone turnover. These bone phenotypes of hpg and orchidectomized non-hpg mice were all prevented by replacement doses of T or dihydrotestosterone (DHT), suggesting that these are determined by adult sex steroid hormones. In contrast, a short bone phenotype that could not be prevented by T or DHT treatment was observed in 9-wk-old hpg mice yet not in intact or castrated non-hpg mice. These data suggest a role for the perinatal T surge in determining adult bone length and confirms that adult circulating T determines adult bone density.
authors.affiliation: Department of Medicine at St. Vincent's Hospital, the University of Melbourne and St. Vincent's Institute, Fitzroy, Victoria, Australia. nsims@unimelb.edu.au
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Sims
authors.forename: Karen
authors.initials: K
authors.lastname: Brennan
authors.forename: Jenny
authors.initials: J
authors.lastname: Spaliviero
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Seibel
mesh_terms: D000728:Androgens / Q000172:deficiency*; D000818:Animals; D015519:Bone Density / Q000502:physiology; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D005269:Femur / Q000033:anatomy & histology / Q000378:metabolism; D007006:Hypogonadism / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009919:Orchiectomy; D015675:Osteocalcin / Q000097:blood; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology; D013977:Tibia / Q000033:anatomy & histology / Q000378:metabolism
chemical_list: D000728:Androgens; D013196:Dihydrotestosterone; D015675:Osteocalcin; D013739:Testosterone