The effects of corticotropin, opioid peptides and crude pituitary extract on the production of dehydroepiandrosterone and corticosterone by mature rat adrenal cells in tissue culture.

In order to study the steroidogenic response to pituitary factors, a technique of monolayer tissue culture of mature female rat adrenal cells was used. During the first 24 h, rat adrenal cells produced dehydroepiandrosterone (DHEA) and small amount of corticosterone but in the absence of corticotropin (ACTH), the release of these two steroids were reduced to very low levels. The addition of synthetic alpha-ACTH-(1-24) [0.01-100 ng/ml] elicited a marked increase in the production of both steroids. This stimulating effect was not observed when synthetic methionine and leucine-enkephalins (1-100 ng/ml), human beta-endorphin (1-100 ng/ml) or human beta-lipotropin (1 ng/ml), were added to the culture medium. When these peptides were added concomitantly with alpha-ACTH (1-24) at half of the maximum response dose (1 ng/ml), no synergistic effect upon DHEA and corticosterone production was shown. The addition of crude extract from rat pituitary gland (1-100 ng/ml) with or without alpha-ACTH-(1-24) definitely showed both a stimulatory and synergistic effect upon the production of these two steroids. Furthermore, the ratio between DHEA production and corticosterone production was significantly higher when crude extract of the pituitary gland was given alone or concomitantly with alpha-ACTH(1-24) than when alpha-ACTH(1-24) was given alone. These data suggest the existence of a still undefined pituitary adrenal androgen stimulating which may preferentially stimulate DHEA production over corticosterone production.