妊娠黄体におけるステロイド産生諸酵素の活性に関する研究:-特に流産催起剤投与に際して-

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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 shown to be regulated by the activity of 20α-hydroxysteroid dehydrogenase (20α-HSD), which catabolizes progesterone to 20α-hydroxypregn-4-en-3-one, progestationally inert steroid. In regressing corpora lutea, extensive conversion of progesterone to 20α-hydroxypregn-4-en-3-one occurred with a marked increase in 20α-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 Δ5-3β-hydroxysteroid dehydrogenase (3β-HSD) have been investigated without any remarkable changes in corpora lutea 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 F2α (PGF2α), 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 105,000 g for 60 min. The supernatant solution was assayed for the activities of G 6 PDH, 6-phosphogluconate dehydrogenase (6 PGDH), malic enzyme, ATP citrate lyase, 20α-HSD and pyruvate kinase. The pellet fraction was re-homogenized, and centrifuged at 2,000 g for 5 min. The supernatant solution was used for the assay of 3β-HSD. Complete fetal resorption was observed in all rats treated with PGF2α, while 7 out of 15 rats (47%) treated with both PGF2α and LH-RH maitained 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 PGF2α-treated ones. In agreement with these ultrastructural findings, 20α-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 PGF2α-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 activities of G 6 PDH and malic enzyme were decreased, while 20α-HSD activity was maintained at a low level. When the dose level was increased, complete abortion was observed. In corpora lutea of these rats 20α-HSD was activated moderately and G 6 PDH had a slightly higher activity than control ones, whereas malic enzyme activity fell to much lower level. These changes of enzyme activities were quite similar to those observed in PGF2α-treated ones. In rats treated with clomid the activities of those enzymes concerned with steroidogenesis, G 6 PDH, malic enzyme and ATP citrate lyase decreased moderately as compared with control rats, while 20α-HSD activity was maintained at a very low level. 6 PGDH, 3β-HSD and pyruvate kinase activities were not altered appreciably in these rats. The activities of 20α-HSD in corpora lutea of 1 day post partum rats,
一般社団法人日本内分泌学会の論文

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岡崎武志
京都大学医学部婦人科学産科学教室

妊娠黄体におけるステロイド産生諸酵素の活性に関する研究:-特に流産催起剤投与に際して-

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