STUDIES OF LYSOSOMES. VI. THE EFFECT OF NEUTRAL STEROIDS AND BILE ACIDS ON LYSOSOMES IN VITRO.
STUDIES OF LYSOSOMES. VI. THE EFFECT OF NEUTRAL STEROIDS AND BILE ACIDS ON LYSOSOMES IN VITRO.
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溶酶体的研究。
DOI：
10.1016/0006-2952(65)90225-x
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发表时间：
1965
影响因子：
5.8
通讯作者：
Gerald Weissmann
中科院分区：
文献类型：
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作者：
Gerald Weissmann
已经在蔗糖悬浮液中研究了类固醇激素和胆汁酸对兔肝脏和白细胞颗粒部分中溶酶体释放水解酶的影响。当浓度高于 2.5 × 10−4M 时，类固醇如乙胆醇酮、孕二酮、孕酮、石胆酸和黄体酮被发现会从兔肝颗粒中释放 β-葡萄糖醛酸酶和酸性磷酸酶活性。乙胆甾酮的代谢前体，如睾酮、脱氢表雄酮或 11-去氧皮质醇，在 37° 时活跃，但在 20° 时不活跃。虽然这些 5-β-H 和 Δ4,5 或 Δ5,6 类固醇将酶从颗粒释放到悬浮介质中，但没有 5-α-H 异构体（例如雄酮）具有可比的活性。孕烷醇酮或乙胆醇酮的碳11的氧化或羟基化降低了类固醇颗粒的活性。用醋酸皮质醇、醋酸可的松或氯喹预处理肝颗粒可减少乙胆甾醇或黄体酮释放的酸性水解酶。乙胆甾酮和黄体酮均降低了分离的白细胞颗粒悬浮液的表观吸光度，并从颗粒中释放β-葡萄糖醛酸酶，而不会物理破坏大部分颗粒。这些数据与溶酶体被热原类固醇破坏的假设相一致。这种体外作用与它们在人体中引起发烧的能力之间的关系尚未确定。
The effect of steroid hormones and bile acids on the release of hydrolases from lysosomes in granular fractions of rabbit liver and leukocytes has been studied in sucrose suspensions. At concentrations above 2.5 × 10−4M, steroids such as etiocholanolone, pregnanedione, pregnanolone, lithocholic acid, and progesterone were found to release β-glucuronidase and acid phosphatase activity from granules of rabbit liver. Metabolic precursors of etiocholanolone, such as testosterone, dehydroepiandrosterone, or 11-desoxycortisol, were active at 37° but not at 20°. Whereas these 5-β-H and Δ4,5 or Δ5,6 steroids released enzymes from the granules into the suspending medium, no 5-α-H isomer, such as androsterone, had comparable activity. Oxygenation or hydroxylation of carbon-11 of pregnanolone or etiocholanolone decreased the activity on the granules of the steroids. Pretreatment of liver granules with cortisol acetate, cortisone acetate, or chloroquine diminished the release of acid hydrolases by etiocholanolone or progesterone. Both etiocholanolone and progesterone reduced the apparent absorbance of suspensions of isolated leukocyte granules, and released β-glucuronidase from the particles, without physically disrupting the majority of granules. The data are compatible with the hypothesis that lysosomes are disrupted by pyrogenic steroids; the relationship of this actionin vitroto their fever-provoking capacity in man has yet to be determined.