Adrenocorticotropin and beta-endorphin release from rat adenohypophysis in vitro: inhibition by prostaglandin E2 formed locally in response to vasopressin and corticotropin-releasing factor.
The present study examined the involvement of prostaglandins (PGs) in the mechanisms of ACTH and beta-endorphin release from rat anterior pituitary quarters incubated in vitro. Various cyclooxygenase inhibitors (indomethacin, diclofenac, flurbiprofen) had no effect on basal release of ACTH-like or beta-endorphin-like immunoreactivity (beta-EI), but enhanced ACTH-immunoreactivity/beta-EI release upon stimulation by arginine-vasopressin (AVP) or synthetic ovine corticotropin-releasing factor [CRF-(1-41)]. The lowest effective concentration of indomethacin was just sufficient to prevent PG synthesis. Indomethacin was similarly active after blockade of the phosphodiesterase by 3-isobutyl-1-methylxanthine. When added to the incubation media in concentrations up to 1 microM, PGE2, D2, F2 alpha, or prostacyclin (PGI2) did not alter basal beta-EI release; however, with stimulation by AVP or CRF-(1-41), PGE2 but not PGD2, F2 alpha, or I2 inhibited beta-EI release by about 60%. The concentrations of PGE2 in the incubation media, as measured by RIA, were somewhat higher than those of any other cyclooxygenase product (PGD2, F2 alpha, 6-keto-PGF1 alpha, thromboxane B2). Upon stimulation by AVP or CRF-(1-41), the concentrations of PGE2 increased, whereas those of PGD2 or F2 alpha remained unchanged. The release of beta-EI stimulated by high potassium concentration was not enhanced by indomethacin, although this release was sensitive to inhibition by PGE2. We conclude that PGE2 is formed locally subsequent to binding of the neurohormones and may act as a negative feedback-modulator of vasopressin's and CRF-(1-41)'s activity in the anterior pituitary gland.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac / Q000494:pharmacology; D015237:Dinoprost; D015232:Dinoprostone; D004723:Endorphins / Q000378:metabolism*; D005480:Flurbiprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin
D016861:Cyclooxygenase Inhibitors; D004723:Endorphins; D011458:Prostaglandins E; D011460:Prostaglandins F; D001127:Arginine Vasopressin; D004008:Diclofenac; D005480:Flurbiprofen; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D015237:Dinoprost; D015232:Dinoprostone; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin