卵巢胆固醇酯生物合成的调控

Control of ovarian cholesterol ester biosynthesis.

作者信息

Flint A P, Grinwich D L, Armstrong D T

出版信息

Biochem J. 1973 Feb;132(2):313-21. doi: 10.1042/bj1320313.

DOI:10.1042/bj1320313

PMID:4353446

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1177589/

Abstract

Experimental evidence is presented for a role of progesterone and 20alpha-hydroxypregn-4-en-3-one as inhibitors of cholesterol ester synthetase in the acute depletion of ovarian cholesterol ester after trophic stimulation. 2. Luteinizing hormone in vitro decreased by 84% the rate of esterification of cholesterol with added [(14)C]oleate by slices of rabbit ovarian interstitial tissue; this effect was mimicked by cyclic AMP (adenosine 3':5'-cyclic monophosphate) in vitro, and occurred without large changes in precursor pool sizes or membrane permeability. 3. Cyclic AMP was shown to have no direct effect on cholesterol ester synthetase or cholesterol esterase in cell-free extracts of rabbit ovarian interstitial tissue, but decreased the activity of cholesterol ester synthetase (not that of cholesterol esterase) in extracts prepared from slices previously incubated with it. 4. The inhibitory effect of cyclic AMP on esterification of cholesterol with added [(14)C]-oleate was prevented by both cycloheximide and aminoglutethimide phosphate (which also inhibited steroid synthesis in response to cyclic AMP). 5. Cyclic AMP raised the intracellular concentrations of progesterone and 20alpha-hydroxypregn-4-en-3-one in incubated slices by factors of 2.8 and 3.9 respectively. 6. Cycloheximide and aminoglutethimide phosphate administered in vivo blocked cholesterol ester depletion in response to luteinizing hormone in rats; in these ovaries cycloheximide and aminoglutethimide phosphate decreased the concentrations of progesterone and 20alpha-hydroxypregn-4-en-3-one and luteinizing hormone raised them. 7. Progesterone and 20alpha-hydroxypregn-4-en-3-one added to cell-free extracts of rabbit ovarian interstitial tissue in vitro (at concentrations comparable with those found in incubated slices) inhibited cholesterol ester synthetase by up to 85%. 8. The results are discussed with reference to the acute control of cholesterol ester concentrations in the ovary and adrenal cortex.

摘要

有实验证据表明，孕酮和20α - 羟基孕-4-烯-3-酮在营养刺激后卵巢胆固醇酯的急性消耗中作为胆固醇酯合成酶的抑制剂发挥作用。2. 体外实验中，促黄体生成素使兔卵巢间质组织切片中添加的[(14)C]油酸与胆固醇的酯化速率降低了84%；环磷酸腺苷（腺苷3':5'-环一磷酸）在体外模拟了这种作用，且发生时前体池大小和膜通透性没有大幅变化。3. 环磷酸腺苷对兔卵巢间质组织无细胞提取物中的胆固醇酯合成酶或胆固醇酯酶没有直接影响，但降低了先前用其孵育过的切片提取物中胆固醇酯合成酶的活性（而非胆固醇酯酶的活性）。4. 环磷酸腺苷对添加[(14)C]油酸的胆固醇酯化的抑制作用被放线菌酮和磷酸氨基谷氨酰胺（它们也抑制响应环磷酸腺苷的类固醇合成）所阻止。5. 环磷酸腺苷使孵育切片中的孕酮和20α - 羟基孕-4-烯-3-酮的细胞内浓度分别提高了2.8倍和3.9倍。6. 体内给予放线菌酮和磷酸氨基谷氨酰胺可阻断大鼠对促黄体生成素的反应中胆固醇酯的消耗；在这些卵巢中，放线菌酮和磷酸氨基谷氨酰胺降低了孕酮和20α - 羟基孕-4-烯-3-酮的浓度，而促黄体生成素则提高了它们的浓度。7. 体外向兔卵巢间质组织的无细胞提取物中添加孕酮和20α - 羟基孕-4-烯-3-酮（浓度与孵育切片中发现的浓度相当）可使胆固醇酯合成酶的活性抑制高达85%。8. 参考卵巢和肾上腺皮质中胆固醇酯浓度的急性控制对结果进行了讨论。