Adrenocorticotropin andβ-Endorphin Release from Rat Adenohypophysisin Vitro: Inhibition by Prostaglandin E2Formed Locally in Response to Vasopressin and Corticotropin-Releasing Factor*

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Abstract
The involvement of prostaglandins (PG) in the mechanisms of ACTH and .beta.-endorphin release from rat anterior pituitary quarters incubated in vitro was examined. 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 .mu.M. PGE2, PGD2, PGF2.alpha., or prostacyclin (PGI2) did not alter basal .beta.-EI release. 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 radioimmunoassay [RIA] were somewhat higher than those of any other cyclooxygenase product (PGD2, PGF2.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 PGF2.alpha. remained unchanged. The release of .beta.-EI stimulated by high K concentration was not enhanced by indomethacin, although this release was sensitive to inhibition by PGE2. 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.