ACTH and corticosterone secretion following indomethacin, in intact, adrenalectomized and dexamethasone-pretreated male rats.
The present study was designed to determine the role of glucocorticoids in the mediation of the stimulatory effect of indomethacin (IM) on the hypothalamo-hypophyseal-adrenal axis. Intact male rats were treated with a single injection of either dexamethasone (Dex; 20 micrograms/100 g body weight), IM (5 mg/100 g body weight), or IM + Dex or their respective vehicles. In Dex-treated rats, ACTH and corticosterone (CS) were significantly reduced over a period of 20 h as compared to the vehicle-treated group. As we have previously demonstrated, injection of IM markedly elevated serum ACTH and CS for at least 20 h. Administration of Dex 2 h prior to IM treatment delayed the stimulatory effect of IM for 5 h; subsequently, however, Dex was without effect. In adrenalectomized rats, ether stress elicited a marked rise in serum ACTH levels. On the contrary, IM was completely ineffective in these rats. These studies suggest that the mode of action of IM in causing hypersecretion of ACTH and CS is by interfering with the negative feedback effects of the glucocorticoids.
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D011458:Prostaglandins E; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D015232:Dinoprostone; D003345:Corticosterone; D007213:Indomethacin