Lanoux M J, Cleland W H, Mendelson C R, Carr B R, Simpson E R
Endocrinology. 1985 Jul;117(1):361-8. doi: 10.1210/endo-117-1-361.
The purpose of the present investigation was to characterize and determine what hormones affect the activity of aromatase in human fetal hepatocytes maintained in primary monolayer culture. The major product of aromatization of androstenedione was estrone sulfate. Optimal conditions for assay of aromatase activity in fetal liver cells were determined. The apparent Km for androstenedione was 50 nM. Aromatase activity was stimulated by glucocorticoids in the presence of fetal calf serum. The concentration of dexamethasone required for half-maximal stimulation was 10(-8) M, similar to the concentration required for half-maximal binding to glucocorticoid receptors. This action of dexamethasone was inhibited by cortisol 21-mesylate, a glucocorticoid antagonist. Aromatase activity was also stimulated by (Bu)2cAMP and cholera toxin, and was inhibited by fetal calf serum. This effect of fetal calf serum was mimicked by epidermal growth factor. However, epidermal growth factor did not mimic the permissive action of serum to stimulate aromatase activity by dexamethasone. In these respects, the regulation of aromatase activity of human fetal hepatocytes is similar to that of human adipose stromal cells. A polycyclic hydrocarbon, benzo(a)pyrene, which causes induction of aryl hydrocarbon hydroxylase activity in fetal hepatocytes, inhibited the stimulation of aromatase activity by dexamethasone. Of a number of hormones tested, including glucagon, insulin, angiotensin II, ACTH, hCG, GH, PRL, and T3, only glucocorticoids were effective in stimulating aromatase activity of human fetal hepatocytes. These results emphasize the complex and multiparameter nature of the regulation of aromatase activity in this as in other tissues.
本研究的目的是表征并确定哪些激素会影响原代单层培养的人胎儿肝细胞中芳香化酶的活性。雄烯二酮芳香化的主要产物是硫酸雌酮。确定了胎儿肝细胞中芳香化酶活性测定的最佳条件。雄烯二酮的表观 Km 为 50 nM。在胎牛血清存在的情况下，糖皮质激素可刺激芳香化酶活性。半数最大刺激所需的地塞米松浓度为 10(-8) M，与半数最大结合糖皮质激素受体所需的浓度相似。地塞米松的这一作用被糖皮质激素拮抗剂甲磺酸皮质醇抑制。(Bu)2cAMP 和霍乱毒素也可刺激芳香化酶活性，而胎牛血清则抑制该活性。表皮生长因子可模拟胎牛血清的这一作用。然而，表皮生长因子不能模拟血清对通过地塞米松刺激芳香化酶活性的允许作用。在这些方面，人胎儿肝细胞中芳香化酶活性的调节与人类脂肪基质细胞相似。一种多环烃苯并(a)芘可诱导胎儿肝细胞中芳烃羟化酶活性，它抑制了地塞米松对芳香化酶活性的刺激。在测试的多种激素中，包括胰高血糖素、胰岛素、血管紧张素 II、促肾上腺皮质激素、人绒毛膜促性腺激素、生长激素、催乳素和三碘甲状腺原氨酸，只有糖皮质激素能有效刺激人胎儿肝细胞的芳香化酶活性。这些结果强调了该组织以及其他组织中芳香化酶活性调节的复杂性和多参数性质。
