Di Blasio A M, Jaffe R B
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143.
Biol Reprod. 1988 Oct;39(3):617-21. doi: 10.1095/biolreprod39.3.617.
We investigated whether human fetal adrenal cells pretreated with or continuously exposed to adrenocorticotropic hormone (ACTH) would develop refractoriness of the steroidogenic response. Fetal adrenal glands from fetuses of 18-24 wk gestation, were studied. Fetal zone cells were pretreated with increasing doses of ACTH (0-10(-6) M) for 24 h and then restimulated with a single dose of ACTH (10(-6) M) for an additional 24 h. Regardless of the dose of ACTH in the first incubation, the cells responded to the second stimulation with a 2- to 6-fold increase in dehydroepiandrosterone sulfate (DHAS) production. When human fetal adrenal cells were incubated in the continuous presence of 10(-8) M ACTH for 72 h, DHAS production was increased compared to that of the untreated cultures (5-fold at 24 h and 50-fold at 72 h), and the cells remained responsive during the entire experimental period. In contrast, human adult adrenal cells showed a significant decrease of the steroidogenic response after 48 h of ACTH treatment. Twenty-four hours of incubation with increasing doses of ACTH also increased the basal steroidogenic capacity of the fetal adrenal cells. One of the steroidogenic enzymatic steps stimulated by ACTH pretreatment was that of 17 alpha-hydroxylase/17, 20-lyase, since conversion of pregnenolone and 17 alpha-hydroxypregnenolone to DHAS was increased in a dose-dependent manner. These results demonstrate that human fetal adrenal cells, in contrast to those of the adult, do not become desensitized to ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了经促肾上腺皮质激素（ACTH）预处理或持续暴露的人胎儿肾上腺细胞是否会出现类固醇生成反应的不应性。对妊娠18 - 24周胎儿的肾上腺进行了研究。将胎儿带区细胞用递增剂量的ACTH（0 - 10⁻⁶ M）预处理24小时，然后再用单剂量ACTH（10⁻⁶ M）再刺激24小时。无论首次孵育时ACTH的剂量如何，细胞对第二次刺激的反应是硫酸脱氢表雄酮（DHAS）生成增加2至6倍。当人胎儿肾上腺细胞在10⁻⁸ M ACTH持续存在下孵育72小时时，与未处理的培养物相比，DHAS生成增加（24小时时增加5倍，72小时时增加50倍），并且细胞在整个实验期间仍保持反应性。相比之下，成人肾上腺细胞在ACTH处理48小时后类固醇生成反应显著降低。用递增剂量的ACTH孵育24小时也增加了胎儿肾上腺细胞的基础类固醇生成能力。ACTH预处理刺激的类固醇生成酶促步骤之一是17α - 羟化酶/17,20 - 裂解酶，因为孕烯醇酮和17α - 羟孕烯醇酮向DHAS的转化呈剂量依赖性增加。这些结果表明，与人成年肾上腺细胞不同，人胎儿肾上腺细胞不会对ACTH产生脱敏。（摘要截短于250字）
