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Parathyroid Hormone Inhibitors: Comparison of Biological Activity in Bone- and Skin-Derived Tissue^*

STEVEN R. GOLDRING, JANE E. MAHAFFEY, MICHAEL ROSENBLATT, JEANMICHEL DAYER, JOHN T. POTTS, JR. and STEPHEN M. KRANE

Department of Medicine, Harvard Medical School, and the Medical Services (Arthritis and Endocrine Units), Massachusetts General Hospital, Boston, 02114; and the New England Deaconess Hospital, Boston, Massachusetts 02215

To evaluate the biological properties of parathyroid hormone (PTH) and two synthetic inhibitors of PTH, monolayer cell cultures derived from two human tissues were utilized. One cell culture system was prepared from human giant cell tumors of bone and the other from human neonatal foreskin. The level of cAMP was increased in cells obtained from both of these tissues when the cell cultures were incubated with PTH. The apparent affinity constants for PTH (1.2 x 10⁸ and 1.6 x 10⁸ M in dermal and tumor-derived cells, respectively) and the concentrations of the synthetic PTH analogs which produced 50% inhibition of PTH-induced increases in cAMP content in the two human cell cultures (5 x 10⁸ and 8 x 10⁸ M for the analog [Nle-8, Nle-18, Tyr-34]bovine PTH-(3-34) amide in dermal and tumor-derived cells, respectively) were nearly identical to the values previously observed in studies employing membranes prepared from canine renal tissue. Although not regarded as a PTH target tissue, fibroblasts from human neonatal foreskin possessed PTH receptors comparable to those of bone and kidney tissue. This study extends the evaluation of parathyroid inhibitors to cells in monolayer culture and illustrates that such cell culture systems provide a model for investigation of PTH receptor interactions in human tissues. (J Clin Endocrinol Metab 48: 655, 1979)

^* This work was supported in part by NIAMDD Grants AM-03564, AM-04501, and AM-11794.

Teaching and Research Scholar of the American College of Physicians.

Recipient of a National Research Service Award and a Research Fellowship from the Medical Foundation funded by the Godfrey M. Hyams Trust.

Supported by Fond National Suisse de Recherche Scientifique.

Received October 18, 1978.

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