Effect of 3 day infusion of ACTH or CRF on the pituitary-adrenal axis.
1. The effects of 72 h subcutaneous infusion of graded doses of rat CRF and ACTH(1-24) were studied in rats of initial weight 150-170 g. Rat CRF was infused at 30, 100 or 300 ng/h, and ACTH(1-24) at 125, 250 or 500 ng/h. 2. There was a progressive though modest increase in adrenal weight for all CRF doses, and an associated reduction of thymus weight. Circulating ir-ACTH, ir-beta-endorphin and corticosterone levels, and adrenal DNA content, were not increased after 3 days. Adrenal RNA and protein content were increased at the highest CRF dose used. 3. ACTH infusion caused a progressive increase in adrenal weight and thymic involution which was marked at the higher doses; circulating corticosterone levels were not significantly altered by the lowest dose but were significantly raised by the higher doses. As expected, plasma ir-beta-endorphin was suppressed to low levels with all doses. Adrenal DNA did not alter but there were progressive increases in adrenal protein and RNA. 4. There was a marked difference in gain between the two infusion regimens in terms of all parameters measured, suggesting that potent mechanisms exist to temper the pituitary-adrenal response to markedly different levels of peripheral CRF input. The damped effect of CRF infusion compared with that of ACTH may represent desensitization of CRF receptors at the pituitary; alternatively, it may reflect binding and substantial inactivation of CRF in peripheral blood.
Silberberg
S
S
Medical Research Centre, Prince Henry's Hospital, Melbourne, Victoria, Australia.
Funder
J W
JW
D000311:Adrenal Glands / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects / Q000254:growth & development; D001615:beta-Endorphin / Q000097:blood
D010455:Peptides; D011506:Proteins; D001615:beta-Endorphin; D012313:RNA; D000324:Adrenocorticotropic Hormone; D004247:DNA; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone