Corticosteroidogenesis and adenosine 3', 5'- monophosphate production by the amino-terminal (1-34) fragment of human parathyroid hormone in rat adrenocortical cells.
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 collagenase-dissociated 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.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D019379:Teriparatide / Q000031:analogs & derivatives
D000305:Adrenal Cortex Hormones; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; C025076:parathyroid hormone (1-34), bovine; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; C035748:parathyroid hormone (1-34)amide