摘要
本文用消旋棉酚及其旋光异构体比较研究了对纯化小鼠肝脏LDH-A_4,心脏LDH-B_4和睾丸LDH-C_4的抑制作用。其抑制程度与实验温度和棉酚剂量有关。37℃时的抑制作用比25℃时强得多。棉酚低浓度(1～4μM)时三种酶对同一种棉酚的反应有明显的不同,而在较高棉酚浓度(20～100μM)时棉酚对三种酶的抑制作用大体相同。对同一种酶来说,消旋棉酚,右旋棉酚和左旋棉酚对LDH的抑制作用并无差异。结论是,棉酚及其旋光异构体并不特异地抑制LDH-C_4,而在离体试验中,不能反映棉酚在体内试验中所表现的光学立体结构特异性。
Gossypol is a potential male antifertility agent. It can inhibit sperm specific lactate
dehydrogenase C4 (LDH-C4 or LDH-X) in mammals. Therefore, it has been supposed
that LDH-C4 is a target enzyme of gossypol action. The investigations of gossypol
antifertility effect indicated that only (-) -gossypol revealed antifertility effect, but not
(+) -gossypol.
In order to understand the mechanism of gossypol antifertility effects with respect to
enzymology, comparative studies on the inhibitory effect of gossypol and its isomers on
LDH isozymes were carried out.
Our results clearly indicated that both gossypol and its isomers had a remarkable inhi-
bitory effect on these isozymes. The inhibition was temperature- and dose-dependent. The
inhibitory effect on these isozymes was much stronger at 37℃ than at 25℃. The concen-
trations of gossypol required for 50% inhibition of LDH-C4 were 56μM at 37℃ and
2.1μM at 25℃.
Regarding the extent or response of the isozymes to gossypol and its isomers, remark-
able differences between these isozymes were observed at low concentrations of gossypol
and its isomers (1μM-4μM, at 37℃), but at high concentrations (20μM-100μM, 25
℃), there was no significant difference observed in the extent of inhibition of gossypol
on LDH-A4, LDH-C4 and LDH-B4.
Our studies also indicated that in the whole range of concentrations of gossypols at
the two indicated temperatures, the extent of inhibition on each of the isozymes was al-
most the same for LDH-A4, LDH-B4 and LDH-C4. No significant difference of inhibi-
tion on each of the isozymes was found between gossypol and its isomers. In other words,
the 3 gossypols possessed similar affinity to the same isozyme.
In conclusion, gossypol and its isomers do not specifically inhibit sperm-specific lacta-
te dehydrogtnase C4, which cannot be considered a target enzyme of gossypol action.
Moreover, gossypol does not have stereo-specificity in its inhibitory effect on LDH-C4
isozyme.
出处
《生殖与避孕》
CAS
CSCD
北大核心
1991年第1期20-25,共6页
Reproduction and Contraception
基金
联合国人口活动基金
世界卫生组织资助
