A direct inhibitory action of prostaglandins upon ACTH secretion at the late stages of the secretory pathway of AtT‐20 cells

Abstract

The mouse AtT‐20/D16‐16 anterior pituitary tumour cell line was used as a model system for the study of the effects of prostaglandins upon the late stages of the adrenocorticotrophin (ACTH) secretory pathway. Calcium (1 nM – 100 μM), guanosine‐5′‐O‐(3‐thiotriphosphate) (GTP‐γ‐S) (1 – 100 μM) and mastoparan (1 and 10 μM) all stimulated ACTH secretion from permeabilized AtT‐20 cells in a concentration‐dependent manner. GTP‐γ‐S and mastoparan stimulated ACTH secretion from permeabilized cells in the absence of calcium. Co‐incubation with prostaglandins E1 and E2 (PGE1, PGE2) (10 μM) but not prostaglandin F2α (PGF2α) (10 μM) significantly inhibited calcium‐, GTP‐γ‐S and mastoparan‐evoked secretion by 30 – 50%. The effects of PGE1 and PGE2 upon GTP‐γ‐S (100 μM)‐, calcium (10 μM)‐ and mastoparan (10 μM)‐evoked secretion were concentration‐dependent. PGE1 significantly inhibited GTP‐γ‐S‐ and calcium‐evoked secretion at concentrations of PGE1 above 1 μM but mastoparan‐evoked secretion only at the highest concentration of PGE1 investigated (10 μM). PGE2 was much more potent than PGE1 and significantly inhibited GTP‐γ‐S‐ and calcium‐evoked secretion at 10 nM and above and mastoparan‐evoked secretion above 1 μM. The inhibitory effects of PGE1 and PGE2 upon calcium‐, GTP‐γ‐S‐ and mastoparan‐stimulated ACTH secretion from permeabilized cells were pertussis toxin (PTX) sensitive. In intact cells PGE1, PGE2 and PGF2α (1 nM – 10 μM) acting singly had little or no effect upon ACTH secretion. However, only PGE2 (1 nM – 10 μM) significantly inhibited corticotrophin‐releasing factor‐41 (CRF‐41) (100 nM)‐evoked secretion in a concentration dependent manner. The present study finds that prostaglandins of the E series exert an inhibitory action, via a pertussis toxin‐sensitive GTP‐binding (G)‐protein, in the late stages of the ACTH secretory pathway distal to the G‐exocytosis (Ge)/calcium point of control. British Journal of Pharmacology (2002) 135, 1851–1858; doi:10.1038/sj.bjp.0704652

Co-localisation of prostaglandin endoperoxide synthase and immunoreactive adrenocorticotrophic hormone in ovine foetal pituitary

“…There is convincing evidence that metabolites of arachadonic acid can modulate the secretory response to CRH (Cowell et al 1991) and AVP (Brooks 1992, Brooks & Gibson 1992. Studies performed in vitro (Vlaskovska & Knepel 1984, Abou-Samra et al 1986, Wilson & Guild 2002 and in vivo (Hedge 1977) have shown that inhibition of PGE 2 and/or injection of PGE 2 has a direct modulatory effect on corticotropes.…”

A histological study on the effect of noise on the adrenal cortex of adult male guinea pigs and the possible role of combined vitamins (A, C, and E) supplementation

“…This congestion was attributed to an increase in ACTH, which stimulated the formation of prostaglandins leading to congestion [43]. This congestion was attributed to an increase in ACTH, which stimulated the formation of prostaglandins leading to congestion [43].…”