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Silve, C. et al.

Selective resistance to parathyroid hormone in cultured skin fibroblasts from patients with pseudohypoparathyroidism type Ib.

We measured cAMP production in response to agonists in cultured skin fibroblasts from subjects with pseudohypoparathyroidism type Ib ( PHP Ib; normal phenotype, resistance to PTH only, normal guanine nucleotide stimulatory coupling protein activity) and skin fibroblasts from normal subjects. There were no significant differences in basal or prostaglandin E1- and forskolin-stimulated cAMP production in PHP Ib vs. normal fibroblasts. Fibroblasts from 7 of 10 subjects with PHP Ib had significantly reduced peak cAMP responses to PTH [3.95 +/- 0.88 vs. 15.9 +/- 4.2 pmol/100 micrograms protein (mean +/- SD); n = 7 for both groups; P less than 0.001]. PTH- stimulated cAMP production was significantly reduced in the 7 subjects with PHP Ib at all concentrations of PTH tested [3-1000 ng/ml human PTH-(1-34)]. In the other 3 subjects with PHP Ib, the cAMP response to PTH was either normal (2 subjects) or above the normal range (1 subject). Thus, skin fibroblasts from many, but not all, subjects with PHP Ib have selective resistance to PTH in terms of cAMP response. Since the defect is hormone specific and persists in culture, we suggest that an intrinsic defect in the PTH receptor may cause PTH resistance in certain subjects with PHP Ib. The cause of PTH resistance in the subjects with a normal cAMP response to PTH is not known, but the data suggest heterogeneity even within the PHP Ib subgroup.[1]

References

Selective resistance to parathyroid hormone in cultured skin fibroblasts from patients with pseudohypoparathyroidism type Ib. Silve, C., Santora, A., Breslau, N., Moses, A., Spiegel, A. J. Clin. Endocrinol. Metab. (1986) [Pubmed]

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