The present study was undertaken to determine the structure-activity relationships of ACTH analogs on corticosteroid production by frog adrenal gland. Rana ridibunda interrenal dice were perifused with amphibian culture medium for 10 hr. Corticosterone and aldosterone concentrations were measured in the effluent perifusate using sensitive and specific radioimmunoassay methods. Perifusion of interrenal fragments with increasing concentrations of synthetic human ACTH 1-39 (ranging from 6.25 X 10(-11) to 10(-9) M) led to a linear log-dose increase in both corticosterone and aldosterone secretion. Thus, this model made it possible to compare the steroidogenic potency of several ACTH analogs. Synthetic alpha-MSH and its des-N alpha-acetyl derivative were found to be approximately equipotent, and 5 X 10(3) times less active than authentic ACTH. The short-chain analog ACTH 1-10 was 2 X 10(4) times less potent than ACTH whereas ACTH 4-10 was totally inactive. A fragment of the N-terminal region of the proopiomelanocortin molecule, gamma 3-MSH, caused a dose-related stimulation of steroid secretion. However, in contrast to what has been observed in the rat, gamma 3-MSH did not potentiate the corticotropic action of ACTH on frog interrenal gland. Since processing of proopiomelanocortin in frog intermediate lobe generates high amounts of alpha-MSH and des-N alpha-acetyl alpha-MSH, these results suggest that in amphibians, several peptides other than ACTH may be involved in the control of corticosteroidogenesis.
In vitro study of frog (Rana ridibunda Pallas) interrenal function by use of a simplified perifusion system. VIII. Structure activity relationship of synthetic ACTH fragments and gamma-MSH
PERROTEAU, Isabelle;
1986-01-01
Abstract
The present study was undertaken to determine the structure-activity relationships of ACTH analogs on corticosteroid production by frog adrenal gland. Rana ridibunda interrenal dice were perifused with amphibian culture medium for 10 hr. Corticosterone and aldosterone concentrations were measured in the effluent perifusate using sensitive and specific radioimmunoassay methods. Perifusion of interrenal fragments with increasing concentrations of synthetic human ACTH 1-39 (ranging from 6.25 X 10(-11) to 10(-9) M) led to a linear log-dose increase in both corticosterone and aldosterone secretion. Thus, this model made it possible to compare the steroidogenic potency of several ACTH analogs. Synthetic alpha-MSH and its des-N alpha-acetyl derivative were found to be approximately equipotent, and 5 X 10(3) times less active than authentic ACTH. The short-chain analog ACTH 1-10 was 2 X 10(4) times less potent than ACTH whereas ACTH 4-10 was totally inactive. A fragment of the N-terminal region of the proopiomelanocortin molecule, gamma 3-MSH, caused a dose-related stimulation of steroid secretion. However, in contrast to what has been observed in the rat, gamma 3-MSH did not potentiate the corticotropic action of ACTH on frog interrenal gland. Since processing of proopiomelanocortin in frog intermediate lobe generates high amounts of alpha-MSH and des-N alpha-acetyl alpha-MSH, these results suggest that in amphibians, several peptides other than ACTH may be involved in the control of corticosteroidogenesis.
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