Casey M L, Howell M L, Winkel C A, Simpson E R, MacDonald P C
J Clin Endocrinol Metab. 1981 Nov;53(5):990-6. doi: 10.1210/jcem-53-5-990.
The levels of deoxycorticosterone (DOC) and DOC-SO4 are extraordinarily high in umbilical cord plasma of human newborns compared to those in plasma of men and nonpregnant women. Progesterone is converted to DOC in minces, homogenates, and microsome-enriched preparations of human fetal kidney tissue. Since DOC, a mineralocorticosteroid, is formed in situ in kidney, its potential site of action, we sought to define whether sulfurylation of DOC also occurred in fetal kidney. We found that radiolabeled DOC-SO4 was formed from [3H]DOC and from [3H]progesterone in minces of human fetal kidneys. C-21 hydroxysteroid sulfotransferase activity was found to be localized principally in the cytosolic fraction of homogenates of human fetal kidney tissue and was present in both the cortical and medullary portions of fetal kidney. In cytosolic fractions prepared from homogenates of human fetal kidneys, we found that the apparent Km of the C-21 hydroxysteroid sulfotransferase for DOC was 4.7 microM; the reaction was linear with time for 60 min and was linear with protein concentration up to 1.2 mg X ml-1 incubation mixture. Thus, DOC-SO4, as well as DOC, is synthesized in the kidney of the human fetus, and kidney may be an important site of formation of these steroids that are found in fetal blood in very high concentrations.
与男性和未怀孕女性的血浆相比,人类新生儿脐带血浆中脱氧皮质酮(DOC)和硫酸脱氧皮质酮(DOC-SO4)的水平极高。在人胎儿肾组织的碎块、匀浆和富含微粒体的制剂中,孕酮可转化为DOC。由于盐皮质激素DOC是在其潜在作用部位——肾脏原位形成的,我们试图确定DOC的硫酸化是否也发生在胎儿肾脏中。我们发现,在人胎儿肾碎块中,放射性标记的DOC-SO4可由[3H]DOC和[3H]孕酮形成。发现C-21羟类固醇硫酸转移酶活性主要定位于人胎儿肾组织匀浆的胞质部分,且在胎儿肾脏的皮质和髓质部分均有存在。在由人胎儿肾匀浆制备的胞质部分中,我们发现C-21羟类固醇硫酸转移酶对DOC的表观Km为4.7 microM;反应在60分钟内与时间呈线性关系,在高达1.2 mg X ml-1孵育混合物的蛋白质浓度范围内与蛋白质浓度呈线性关系。因此,DOC-SO4以及DOC都是在人类胎儿的肾脏中合成的,并且肾脏可能是这些在胎儿血液中以非常高浓度存在的类固醇的重要形成部位。