Fist described by Albright and colleagues [119], Pseudohypoparathyroidism (PHP) refers to end-organ resistance to multiple hormones that primarily involves the actions of parathyroid hormone. PTH exerts its actions in bone and kidney through the PTH/parathyroid hormone-related peptide receptor (PTHR1), which couples to Gs and, less effectively, to Gq [120, 121]. PTH increases bone turnover, leading to mobilization of calcium and phosphate from bone [122, 123]. In the proximal renal tubule, it induces the synthesis of 1,25-dihydroxyvitamin D and inhibits phosphate reabsorption from the glomerular filtrate, while in the distal renal tubule, it enhances the absorption of calcium mediated via transcellular mechanisms. Exogenous administration of biologically active PTH, used previously as a diagnostic test [124], results in a blunted excretion of urinary phosphate in both PHP type-I and PHP type-II, but this defect is accompanied by blunted nephrogenous cAMP production in PHP type-I only; the PTH-induced generation of nephrogenous cAMP is normal in PHP type-II [119, 125]. Clinically, PHP-I is far more frequent than PHP-II, for which underlying molecular defects are not well understood. On the other hand, significant advances have been recently made regarding the molecular pathology underlying PHP-I.
