PTH1R and secondary hyperparathyroidism: Moreover, literature data suggest that GH and IGF-I are capable of directly interacting with the PTHrP/PTH1R/Gsα/cAMP/PKA-signaling pathway in bone cell cultures34-37 and animal models (eg, model for chronic renal failure and severe secondary hyperparathyroidism).38 It is therefore tempting to speculate that rhGH therapy contributes not only to an optimal IGF-I concentration in the growth plate, but also to a decrease, at least in part, in the degree of PTH/PTHrP resistance, by interfering with PTHrP/PTH1R expression and/or function locally.