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[堕胎药处理的早期妊娠大鼠黄体中甾体生成酶活性的研究(作者译)]

[Studies on the activities of steroidogenic enzymes in corpora lutea of early pregnant rats treated with abortifacient drugs (author's transl)].

作者信息

Okazaki T

出版信息

Nihon Naibunpi Gakkai Zasshi. 1975 Oct 20;51(10):813-24. doi: 10.1507/endocrine1927.51.10_813.

Abstract

The major role of the corpus luteum is biosynthesis of progesterone. Luteal function has been investigated by following plasma progesterone concentrations and by studying ultrastructural and histochemical changes in corpora lutea. Recently, changes in enzyme activities concerned with formation and degradation of progesterone are taken into investigation in order to understand the regulation of luteal function. In rat ovaries, progestational potency of ovarian secretions has been regulated by the activity of 20 alpha-hydroxysteroid dehydrgoenase (20 alpha-HSD), Which catabolizes progesterone to 20 alpha-hydroxypregn-4-en-3-one, progestatinally inert steroid. In regressing corpora lutea, extensive conversion of progesterone to 20 alpha-hydroxypregn-4-en-3-one occurred with a marked increase in 20 alpha-HSD activity as well as a decrease in plasma progesterone concentrations. On the other hand, histochemical studies of glucose-6-phosphate dehydrogenase (G 6 PDH) and delta5-3beta-hydroxysteroid dehydrogenase (3 beta-HSD) have been investigated without any remarkable changes in corporalutea at their early stages of luteolysis. In the present study the activities of steroidogenic enzymes in corpora lutea of pregnant rats are measured after treatment with a variety of abortifacient drugs, and compared with those in corpora lutea of 1 day post partum rats which showed changes characteristic of spontaneous luteolysis. On days 7 to 9 of pregnancy, Wistar-strain pregnant rats were injected with either prostaglandin F2alpha (PGF2alpha), aminoglutethimide or clomiphene citrate (clomid). Animals were sacrificed 15 to 63 hrs. after the last injection, and implantation sites were inspected. Ovaries were removed, and corpora lutea dissected free, weighed and homogenized. The homogenate was centrifuged at 105,000g for 60 min. The supernatant solution was assayed for the activities of G 6 PDH, 6-phosphogluconate dehydrogenase (6 PGDH), malic enzyme, ATP citrate lysase, 20 alpha-HSD and pyruvate kinase. The pellet fraction was re-homogenized, and centrifugated 2,000 g for 5 min. The supernatant solution was used for the assay of 3 beta-HSD. Complete fetal resorption was observed in all rats treated with PGF2alpha, while 7 out of 15 rats (47%) treated with both PGF2alpha and LH-RH maintained pregnancy. In intact rats after treatment with both drugs, lutein cells showed ultrastructures characteristic for luteolysis, although the degree of luteolysis was greatly diminished compared with PGF2alpha-treated ones. In agreement with these ultrastructural findings, 20alpha-HSD activity in corpora lutea was maintained at a rather low level in intact rats, while it was increased moderately in aborted ones after treatment with both drugs. In PGF2alpha-treated rats, G 6 PDH activity increased to 140% and malic enzyme activity decreased to 27% of the activity in control rats. In aminoglutethimide-treated rats, the activites of G 6 PDH and malic enzyme were decreased, while 2-alpha-HSD activity was maintained at a low level...

摘要

黄体的主要作用是孕酮的生物合成。通过追踪血浆孕酮浓度以及研究黄体的超微结构和组织化学变化来研究黄体功能。最近,为了了解黄体功能的调节,人们对与孕酮形成和降解有关的酶活性变化进行了研究。在大鼠卵巢中,卵巢分泌物的孕激素活性受20α-羟类固醇脱氢酶(20α-HSD)活性的调节,该酶将孕酮分解代谢为20α-羟基孕-4-烯-3-酮,这是一种无孕激素活性的类固醇。在退化的黄体中,孕酮大量转化为20α-羟基孕-4-烯-3-酮,同时20α-HSD活性显著增加,血浆孕酮浓度降低。另一方面,对葡萄糖-6-磷酸脱氢酶(G 6 PDH)和δ5-3β-羟类固醇脱氢酶(3β-HSD)的组织化学研究表明,在黄体溶解早期,黄体没有明显变化。在本研究中,用各种堕胎药物处理妊娠大鼠的黄体后,测量其类固醇生成酶的活性,并与产后1天大鼠的黄体进行比较,后者表现出自发性黄体溶解的特征性变化。在妊娠第7至9天,给Wistar品系的妊娠大鼠注射前列腺素F2α(PGF2α)、氨鲁米特或枸橼酸氯米芬(克罗米芬)。在最后一次注射后15至63小时处死动物,并检查着床部位。取出卵巢,分离出黄体,称重并匀浆。匀浆液在105,000g下离心60分钟。测定上清液中G 6 PDH、6-磷酸葡萄糖酸脱氢酶(6 PGDH)、苹果酸酶、ATP柠檬酸裂解酶、20α-HSD和丙酮酸激酶的活性。将沉淀部分重新匀浆,在2,000g下离心5分钟。用上清液测定3β-HSD的活性。所有用PGF2α处理的大鼠均观察到完全的胚胎吸收,而用PGF2α和LH-RH处理的15只大鼠中有7只(47%)维持妊娠。在用两种药物处理的完整大鼠中,黄体细胞显示出黄体溶解的超微结构特征,尽管与用PGF2α处理的大鼠相比,黄体溶解程度大大降低。与这些超微结构结果一致,完整大鼠黄体中的20α-HSD活性维持在相当低的水平,而在用两种药物处理的流产大鼠中,该活性适度增加。在PGF2α处理的大鼠中,G 6 PDH活性增加到对照大鼠活性的140%,苹果酸酶活性降低到27%。在氨鲁米特处理的大鼠中,G 6 PDH和苹果酸酶的活性降低,而2-α-HSD活性维持在低水平……

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