Powell W A, Challis J R
Gynecol Obstet Invest. 1986;22(2):73-8. doi: 10.1159/000298894.
The output of progesterone by explants of chorion incubated without exogenous precursor was increased in the presence of 20 alpha-dihydroprogesterone (20 alpha-diHP). We have now examined the nature of the 20 alpha-diHP effect. Explants of chorion were incubated with [3H]progesterone and 3 microM non-radiolabelled 20 alpha-diHP to examine the effect of 20 alpha-diHP on progesterone metabolism. Significantly more radioactivity remained as unmetabolized [3H]progesterone compared to chorion incubated in the absence of non-radiolabelled 20 alpha-diHP. There was also a decrease in the output of [3H]-20 alpha-diHP by the explants but no change in the output of a second metabolite of progesterone [3H]-5 alpha-pregnanedione. When explants were incubated with 20 alpha-diHP in the presence of the 3 beta-hydroxysteroid dehydrogenase inhibitor, trilostane, the output of progesterone was significantly greater than with explants incubated with trilostane but without addition of 20 alpha-diHP. Radiochemically pure [3H]progesterone was produced by explants of chorion incubated with [3H]-20 alpha-diHP. We conclude that 20 alpha-diHP may serve as substrate for chorionic progesterone production through 20 alpha-hydroxysteroid dehydrogenase. 20 alpha-diHP, formed from progesterone, may also exert product feedback inhibition on this enzyme.
在没有外源性前体的情况下培养的绒毛膜外植体，在20α-二氢孕酮（20α-diHP）存在时孕酮产量增加。我们现在研究了20α-diHP作用的本质。将绒毛膜外植体与[3H]孕酮和3 microM非放射性标记的20α-diHP一起孵育，以研究20α-diHP对孕酮代谢的影响。与在没有非放射性标记的20α-diHP的情况下培养的绒毛膜相比，作为未代谢的[3H]孕酮保留的放射性明显更多。外植体产生的[3H]-20α-diHP产量也有所下降，但孕酮的第二种代谢产物[3H]-5α-孕烷二酮的产量没有变化。当外植体在3β-羟基类固醇脱氢酶抑制剂曲洛司坦存在下与20α-diHP一起孵育时，孕酮产量明显高于与曲洛司坦但未添加20α-diHP一起孵育的外植体。用[3H]-20α-diHP孵育的绒毛膜外植体产生了放射化学纯的[3H]孕酮。我们得出结论，20α-diHP可能通过20α-羟基类固醇脱氢酶作为绒毛膜孕酮产生的底物。由孕酮形成的20α-diHP也可能对该酶产生产物反馈抑制作用。
