Barbiturates modulate the activity of the pituitary 3 alpha-hydroxysteroid oxidoreductases and inhibit their production of 3 alpha,5 alpha-tetrahydroprogesterone.
Barbiturates modulate the activity of the pituitary 3 alpha-hydroxysteroid oxidoreductases and inhibit their production of 3 alpha,5 alpha-tetrahydroprogesterone.
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巴比妥类药物调节垂体 3α-羟基类固醇氧化还原酶的活性并抑制其产生 3α,5α-四氢孕酮。
DOI：
10.1016/0960-0760(93)90344-v
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Hodges,DR
中科院分区：
文献类型：
--
作者：
Karavolas,HJ;Hodges,DR
本文观察了苯巴比妥钠和巴比妥钠对雌性大鼠垂体前叶颗粒和胞浆5α-二氢孕酮3α-羟类固醇氧化还原酶（3α-HSORs）活性的影响。通过改变3α-HSOR催化的5 α-DHP转化为3α，5 α-THP，这些巴比妥酸盐可以影响3α，5 α-THP的原位合成。3α，5 α-THP对脑GABA A受体具有强的巴比妥类作用。苯巴比妥和3α，5 α-THP均可影响雌性大鼠促性腺激素的释放。在存在苯巴比妥钠（0.1 - 10.0 mM）或巴比妥钠（1.0 - 10.0 mM）的情况下，测定各3α-HSOR活性的体外孵育。由于3α-HSOR活性都催化5α-DHP和3α，5 α-THP的可逆氧化还原，因此我们不仅研究了这些巴比妥酸盐对5α-DHP转化为3α，5 α-THP（还原反应）的影响，而且还研究了3α，5 α-THP向5α-DHP的“逆转化”（氧化反应）。结果表明，苯巴比妥和巴比妥（在较小程度上）在还原和氧化方向上显著影响两种3α-HSORs的活性。在还原方向上，苯巴比妥抑制细胞溶质和颗粒酶的活性（33%），这可能会降低3α，5 α-THP的水平。在氧化方向上，观察到刺激模式（20 - 100%）。因此，这种对3α，5 α-THP氧化转化为5α-DHP的刺激作用（可能也会降低3α，5 α-THP水平）似乎与这些巴比妥酸盐对5α-DHP还原转化为3α，5 α-THP的抑制作用相关。巴比妥钠表现出类似的作用。提示巴比妥类药物可降低垂体前叶3α，5 α-THP水平。结果还表明，降低的3α，5 α-THP水平可能至少部分参与了巴比妥类药物减少促性腺激素释放的可能性。
The effects of sodium phenobarbital and sodium barbital on the activity of the particulate and cytosolic 5α-dihydroprogesterone 3α-hydroxysteroid oxidoreductases (3α-HSORs) of female rat anterior pituitary were investigated. By altering the 3α-HSOR catalyzed conversion of 5α-dihydroprogesterone (5α-DHP) to 3α,5α-tetrahydroprogesterone (3α,5α-THP), these barbiturates could influence the in situ production of 3α,5α-THP. 3α,5α-THP has potent barbiturate-like effects on brain GABAAreceptors. Both phenobarbital and 3α,5α-THP can affect gonadotropin release in female rats. In vitro incubations of each 3α-HSOR activity were assayed in the presence of sodium phenobarbital (0.1 to 10.0 mM) or sodium barbital (1.0 to 10.0 mM). Since both 3α-HSOR activities catalyze the reversible oxidoreduction of 5α-DHP and 3α,5α-THP, we examined the effect of these barbiturates not only on the conversion of 5α-DHP to 3α,5α-THP (reductive reaction) but also on the “back conversion” of 3α,5α-THP to 5α-DHP (oxidative reaction). The results indicate that both phenobarbital and, to a lesser extent barbital, significantly affected the activities of the two 3α-HSORs in both reductive and oxidative directions. In the reductive direction, phenobarbital inhibited the activity (33%) of both cytosolic and particulate enzymes which would presumably decrease the levels of 3α,5α-THP. In the oxidative direction, a pattern of stimulation was observed (20 to 100%). Thus, this stimulatory effect on the oxidative conversion of 3α,5α-THP to 5α-DHP, which would presumably also decrease 3α,5α-THP levels, appears correlated with the inhibitory effect of these barbiturates on the reductive conversion of 5α-DHP to 3α,5α-THP. Sodium barbital exhibited somewhat similar effects. These changes suggest that barbiturates can lower 3α,5α-THP levels in the anterior pituitary. The results also suggest the possibility that lowered 3α,5α-THP levels may be involved, at least in part, in the reduction of gonadotropin release by barbiturates.