Androgens and their relation to calcium regulatory hormones and IGF1

Several older reports concerned direct androgen effects on calcium regulatory hormones. It has been claimed that calcitonin concentrations are lowered in hypogo-nadal men and levels can be increased by testosterone administration (Foresta etal. 1983; 1985). In rats, androgens seem to enhance hypocalcemia induced by calcitonin (Ogata etal. 1970). Concerning parathyroid hormone (PTH) concentrations, an increment under testosterone substitution therapy of hypogonadal men has been reported (Katznelson et al. 1996; Wang etal. 1996; 2001). The skeletal responsiveness to PTH seems to be increased in hypogonadism, as an experimental setting in men receiving a GnRH-agonist demonstrates (Leder et al. 2001). This effect is likely to be indirect and caused by withdrawal of androgenic influence on osteoclast-responsiveness to PTH. In regard to vitamin D, which is under direct influence of PTH, no consistent findings concerning androgenic influence have been reported. Long-term physiological testosterone replacement did not alter 1,25-(OH)2 vitamin D levels in hypogonadal men (Finkelstein etal. 1989; Tenover 1992) while this was observed on a short-term basis in a small uncontrolled study (Hagenfeldt et al. 1992). Altogether, the modulation androgens exert on the effects of calcium regulatory hormones on bone morphogenetic cells seems to be relevant, while direct androgenic influence on the concentrations of these hormones do not seem to play an important role.

Some effects of testosterone on bone tissue maybe facilitated indirectly by growth hormone (GH) and, consequently, insulin-like growth factor type 1 (IGF-1) levels. These hormones have an intrinsic effect on bone tissue, increasing bone mass and density (Baum et al. 1996; Grinspoon et al. 1995; Monson 2003). Administration of androgens to hypogonadal men enhances GH secretion, mediated at the hypothalamic level primarily by promoting GHRH shedding (Bondenelli et al. 2003). Elevation of testosterone levels increases exercise- or GHRH-stimulated GH pulsatility in hypo- and eugonadal men; consecutively, these effects were also observed for IGF-1 concentrations (Fryburg et al. 1997). This appears to be an important issue for assessing the role of the somatotropic axis is important when androgen effects on bone metabolism are investigated.

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