NORMAL PARATHYROID-HORMONE RESPONSIVENESS OF BONE-DERIVED CELLS FROM A PATIENT WITH PSEUDOHYPOPARATHYROIDISM

Pseudohypoparathyroidism (PI-D) is characterized by a lack of response to parathyroid hormone (PTH); however, normal skeletal responsiveness to PTH in some patients with PHP type Ia was previously suggested on the basis of clinical observations, To test this hypothesis, we measur ed cyclic adenosine monophosphate (cAMP) production in response to var ious agonists in bone-derived osteoblast-like (OBL) cells from trabecu lar explants obtained from an iliac crest biopsy of a 25-year-old woma n with PHP, The patient was proved to have PW type Ia on the basis of Albright's hereditary osteodystrophy and decreased activity of stimula tory guanine nucleotide-binding protein (G(s)) in erythrocytes. Respon siveness of the patient's OBL cells was compared with OBL cells from e ight subjects aged 18-39 years who had no evidence of metabolic bone d isease, OBL cells from the patient responded to the following agonists (expressed in multiples of elevation of cAMP, stimulated/basal, mean +/- SE, n = 3): PTH, 3.8 +/- 0.3; forskolin, 8.2 +/- 0.2; and cholera toxin, 56.8 +/- 10.0. These responses were not significantly different from those of control OBL cells: PTH, 4.5 +/- 1.1 (range 2.4-7.5); fo rskolin, 7.7 +/- 1.4; and cholera toxin, 57.9 +/- 16.2. The normal cho lera toxin response indicated the presence of functional Gs. Bone cell s from patients with PHP type Ia may exhibit a normal PTH receptor-cou pled adenylyl cyclase system in vitro despite clinical evidence of imp aired hormone-responsive adenylyl cyclase in other tissues, including the kidney. Skeletal responsiveness to PTH may explain the long period s of spontaneous normocalcemia observed in this patient.