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Corticosteroidogenesis and Adenosine 3',5'- Monophosphate Production by the Amino-Terminal (1–34) Fragment of Human Parathyroid Hormone in Rat Adrenocortical Cells

National Institute for Biological Standards and Control Holly Hill, Hampstead, London NW3 6RB, United Kingdom
Endocrine Unit, Massachusetts General Hospital Boston, Massachusetts 02114

Address requests for reprints to: B. Rafferty, National Institute for Biological Standards and Control, Holly Hill, Hampstead, London NW3 6RB, United Kingdom.

Abstract

Several studies have revealed a variety of interactions between PTH and ACTH. The existence of a significant area of homology in the bioactive regions of the two molecules has been proposed as a possible reason for such interactions. To clarify the relationship, corticosteroidogenic and cAMP accumulative effects of bovine PTH (bPTH 1–84), its amino-terminal fragment (bPTH 1–34), and the amino terminal fragment of human PTH (hPTH 1–34) were compared with ACTH 1–39 by determining their dose-response characteristics in collagenasedissociated adrenocortical cells from rats. bPTH 1–84 and bPTH 1–34 (10^–8–10^–5 M) did not alter steroid production of the cells nor did 10^–6 M bPTH 1–34 affect the steroid response curve to ACTH 1–39. However, the degree of steroidogenesis elicited by hPTH 1–34 over the dose range 3.3 X 10^–7–3.3 X 10^–5 M was the same as that elicited by ACTH 1–39 over the range 10^–11–10^–9 M. cAMP generation with hPTH 1–34 was maximal at 10^–4 M but the correlation between the steroid and cAMP responses with ACTH 1–39 was noticeably different from that with hPTH 1–34. In experiments with ACTH 6–24 (a competitive inhibitor of ACTH 1–39), both steroid and cAMP responses to hPTH 1–34 were greatly reduced. Oxidized hPTH 1–34 did not elicit any steroid production nor did several other peptide hormones (arginine vasopressin, angiotensin II, calcitonin, insulin, GH) at 10^–5 M.

These observations indicate that hPTH 1–34 can exert a direct and specific effect on rat adrenocortical cells revealing the peptide as a full agonist for steroid production in this system. We suggest that it is a combination of sequence homology and conformational structure which permits hPTH 1–34 to interact with, and elicit its response through, the receptor for ACTH 1–39. (Endocrinology 113: 1036,1983)

Received October 18, 1982.

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