Structure-activity relationships of steroids in inducing germinal vesicle breakdown of Atlantic croaker oocytes in...

The effect of alterations of the steroid nucleus on its potency to induce germinal vesicle breakdown (GVBD) of Atlantic croaker oocytes in vitro was investigated. The addition of 17 alpha-, 20 beta-, or 21-hydroxyl groups to the progesterone steroid nucleus enhanced steroid potency to induce GVBD. Whereas the 20 beta-hydroxyl group on the side chain was the most potent single alteration of the progesterone nucleus, the 17 alpha-hydroxyl group seemed to be vital for establishing the proper steric orientation of the side chain. The most potent steroids to induce GVBD contained either the 17 alpha,20 beta-dihydroxy or the 17 alpha,20 beta,21-trihydroxy configuration. Steroids of the 3-keto-delta 4 and the 3 beta-hydroxy-delta 5 configuration had similar potency. In addition, the 3 beta-hydroxysteroid dehydrogenase inhibitor, cyanoketone, did not affect human chorionic gonadotropin-induced GVBD. However, other alterations of the A and B rings of the steroid nucleus resulted in diminished potency (3 alpha-hydroxy, 5 alpha, and 5 beta configurations). Addition of hydroxyl groups at the 11 beta, 16 alpha, or 20 alpha positions resulted in steroids with reduced potency. The low potency of steroids lacking the side chain (estrogens and androgens) and steroids with the side chain in the 17 alpha position (progestin analogs) is further evidence that the side chain configuration is important for biological activity. Human chorionic gonadotropin and other gonadotropin preparations induced GVBD of croaker oocytes in vitro which indicates that the maturational steroid is of ovarian origin. The finding that 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one (20 beta-S), a major steroid product of croaker oocytes during final oocyte maturation, is a potent inducer of GVBD suggests that it may function as a maturation-inducing steroid in this species.