In vivo adrenocorticotropin (1-24)-induced accumulation of cyclic adenosine monophosphate by ovine fetal adrenal cells is inhibited by concomitant infusion of metopirone.
Activation of the ovine fetal adrenal gland after pulse ACTH (P-ACTH) administration is associated with an increase in plasma cortisol levels. We have investigated whether cortisol may play a role in this adrenal activation process. The ability of fetal adrenal cells to accumulate cAMP in response to ACTH in vitro was compared in fetuses (day 132 of gestation) that had received infusions (100 h) in utero of 1) saline or saline + tartrate (0.5 ml for 15 min/2 h) (n = 4); 2) P-ACTH (66.6 ng/min for 15 min/2 h) (n = 4); 3) P-ACTH + metopirone (31.3 mg/h) (n = 4), to inhibit 11 beta-hydroxylase activity. Control fetuses showed no significant increase in plasma cortisol levels throughout the infusion and there was no significant accumulation of cAMP by fetal adrenal cells in vitro in response to ACTH. There was a significant (P less than 0.05) increase in plasma cortisol concentrations from 2.21 +/- 0.47 (mean +/- SEM) ng/ml at 0 h to 35.7 +/- 11.6 ng/ml at 96 h in fetuses receiving P-ACTH in vivo. In these fetuses there was a significant (P less than 0.05) accumulation of cAMP after addition of ACTH by fetal adrenal cells in vitro (mean increment delta = 48 pmol). This rise in plasma cortisol was prevented in fetuses receiving P-ACTH + metopirone. Further, metopirone treatment prevented the increase in fetal adrenal weight and accumulation of cAMP after in vitro ACTH that normally followed ACTH treatment in vivo. This effect was not overcome by further addition of guanylylimido-diphosphate. These experiments raise the possibility that cortisol might mediate the increase in cAMP accumulation resultant upon in vivo P-ACTH treatment.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects / Q000196:embryology*; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives*; D000818:Animals; D003366:Cosyntropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D008797:Metyrapone / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012756:Sheep; D013997:Time Factors
D003366:Cosyntropin; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine; D006854:Hydrocortisone; D008797:Metyrapone