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

Previous work with mammalian and frog adrenocortical tissue and cells indicates that prostaglandins (PGs) can directly stimulate corticosteroidogenesis. 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 determine whether PGs can directly influence avian corticosteroidogenesis as well. Cells (1 x 10(5) cells/ml) were incubated with a wide range of concentrations of PGs in the presence of indomethacin (1 microg/ml) (to attenuate endogenous PG production) and 1-methyl-3-isobutylxanthine (0.5 mM) [to preserve cyclic AMP (cAMP)] for 2 h. Corticosterone and cAMP production were measured by highly specific radioimmunoassay. PGI2 was without effect. With the exception of PGF2alpha, which had a slight stimulation in chicken but not in turkey cells, the influence of the other PGs on corticosterone production was biphasic. For the stimulatory phase (up to a concentration of 5 x 10(-5) M), there were prostanoid structural and avian species differences in both potency and efficacy of PGs. Overall, PGs were 11 times more potent in turkey cells than in chicken cells. However, the order of potency for stimulation was similar for both chicken and turkey cells: for chicken cells the order was PGE2 > PGE1 > PGA1 > PGB2 > PGB1 > PGF2alpha and for turkey cells it was PGE2 > PGE1 > PGA1 > PGB2 = PGB1. In contrast, PG efficacy for stimulation was greater for chicken cells. In addition, the orders of efficacy were different from the orders of potency. In chicken cells, the order of efficacy was PGE2 = PGA1 > PGE1 > PGB2 > PGB1 > PGF2alpha and for turkey cells it was PGB2 = PGE2 > PGA1 > PGE1 > PGB1. Because of the greater maximal corticosterone response over basal production of chicken cells to PGs, they were used to assess the interaction 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) steroidogenic concentrations of ACTH. With the exception of PGF2alpha, the average efficacy of PGs to elevate corticosterone was increased 55% by a threshold steroidogenic concentration of ACTH. However, with higher concentrations of ACTH, this enhancement of efficacy disappeared as did the stimulatory effect of some PGs. The results suggest that the steroidogenic actions of PGs and ACTH converge on the same pool of steroidogenic enzymes leading to corticosterone. At concentrations greater than 5 x 10(-5) M, several PGs (notably PGA1, PGA2, PGB1, and PGB2) inhibited both ACTH-induced and basal corticosterone production. PGA1 and PGA2 were the most potent inhibitors. Corticosterone and cAMP production were closely associated in the biphasic action of PGs, suggesting that the effect of PGs was mediated by the changing levels of intracellular cAMP. Collectively, these data suggest that PGs may be important modulators of corticosteroidogenesis in the avian adrenal gland.