Concentration-dependent, biphasic effect of prostaglandins on avian corticosteroidogenesis in vitro

Previous work with mammalian and frog adrenocortical tissue and cells indic ates that prostaglandins (PGs) can directly stimulate corticosteroidogenesi s. However, work with avian adrenal preparations is absent. Therefore, the present studies with isolated chicken (Gallus gallus domesticus) and turkey (Meleagris gallopavo) adrenal steroidogenic cells were conducted to determ ine whether PGs can directly influence avian corticosteroidogenesis as well . Cells (1 x 10(5) cells/ml) were incubated with a nide range of concentrat ions of PGs in the presence of indomethacin (1 mu g/ml) (to attenuate endog enous PG production) and 1-methyl-3-isobutylxanthine (0.5 mM) [to preserve cyclic AMP (cAMP)] for 2 h. Corticosterone and cAMP production were measure d by highly specific radioimmunoassay. PGI(2) was without effect. With the exception of PGF(2 alpha), which had a slight stimulation in chicken but no t in turkey cells, the influence of the other PGs on corticosterone product ion was biphasic. For the stimulatory phase (up to a concentration of 5 x 1 0(-5) M), there were prostanoid structural and avian species differences in both potency and efficacy of PGs. Overall, PGs were 11 times more potent i n turkey cells than in chicken cells. However, the order of potency for sti mulation was similar for both chicken and turkey cells: for chicken cells t he order was PGE(2) > PGE(1) > PGA(1) > PGB(2) > PGB(1) > PGF(2 alpha) and for turkey cells it was PGE2 > PGE(1) > PGA(1) > PGB(2) = PGB(1). In contra st, PG efficacy for stimulation was greater for chicken cells. In addition, the orders of efficacy were different from the orders of potency. In chick en cells, the order of efficacy was PGE(2) = PGA(1) > PGE(1) > PGB(2) > PGB (1) > PGF(2 alpha) and for turkey cells it was PGB(2) = PGE(2) > PGA(1) > P GE(1) > PGB(1). Because of the greater maximal corticosterone response over basal production of chicken cells to PGs, they were used to assess the int eraction of PGs with ACTH and to examine more fully the inhibitory phase of PGs. Cells were incubated with PGs in the presence of threshold (2.5 x 10( -11) M), half-maximal (1 x 10(-10) M), and maximal (1 x 10(-7) M) steroidog enic concentrations of ACTH. With the exception of PGF(2 alpha), the averag e efficacy of PGs to elevate corticosterone was increased 55% by a threshol d steroidogenic concentration of ACTH. However, with higher concentrations of ACTH, this enhancement of efficacy disappeared as did the stimulatory ef fect of some PGs. The results suggest that the steroidogenic actions of PGs and ACTH converge on the same pool of steroidogenic enzymes leading to cor ticosterone. At concentrations greater than 5 x 10(-5) M, several PGs (nota bly PGA(1), PGA(2), PGB(1), and PGB(2)) inhibited both ACTH-induced and bas al corticosterone production. PGA, and PGA(2) were the most potent inhibito rs. Corticosterone and cAMP production were closely associated in the bipha sic action of PGs, suggesting that the effect of PGs was mediated by the ch anging levels of intracellular cAMP. Collectively, these data suggest that PGs may be important modulators of corticosteroidogenesis in the avian adre nal gland. (C) 1999 Academic Press.