Challis J R, Manchester E L, Mitchell B F, Patrick J E
Biol Reprod. 1982 Dec;27(5):1026-32. doi: 10.1095/biolreprod27.5.1026.
We determined whether ACTH1-24, infused into fetal lambs at a rate that is known to cause premature labor, elicits changes in the responsiveness of the fetal adrenal glands, and alters the pattern of corticosteroid output. Plasma cortisol (F), corticosterone (B) and progesterone (P4) were measured during 72 h of infusion of saline or ACTH (10 micrograms/h) beginning on Day 127 of pregnancy. Adrenals were then dispersed into isolated cells, and the output of F, B and P4 after exogenous ACTH determined in vitro. Plasma concentrations of F and B were higher in ACTH-treated fetuses. The increment in F (5-to 7-fold) was greater than that in B (2-fold) such that the F:B ratio in plasma of ACTH-treated fetuses on Days 2 and 3 of infusion was 2.5 times higher than in controls. After 72 h of infusion, the adrenal weights in ACTH-treated fetuses (741 +/- 38 mg, +/- SEM; n = 4) were greater than in the control animals (349 +/- 11 mg). There was a significant effect of ACTH pretreatment in vivo on F output by isolated adrenal cells in vitro. Mean increments in F output after addition of ACTH1-24 (5000 pg/ml) in vitro rose from 368 +/- 235 pg/50,000 cells in controls, to 64,639 +/- 19,875 pg/50,000 cells after ACTH in vivo. There was no significant effect of ACTH in vivo on B output in vitro; the ratio of F:B output, either in the absence or presence of ACTH in vitro, was significantly higher in cells from ACTH-pretreated fetuses. There was a significant effect of in vivo ACTH on in vitro P4 output. After ACTH treatment in vivo there was an increase in the vitro output ratio of F:P4, but no change in the output ratio of B:P4. We conclude that ACTH treatment of the fetal lamb in vivo results in activation of fetal adrenal function, increased fetal adrenal responsiveness to ACTH, and directed corticosteroid biosynthesis towards cortisol. Our results are consistent with an increase in fetal adrenal 17 alpha-hydroxylase activity after ACTH treatment.
我们研究了以已知可导致早产的速率向胎羊输注促肾上腺皮质激素（ACTH）1 - 24 是否会引起胎羊肾上腺反应性的变化，并改变皮质类固醇的分泌模式。在妊娠第127天开始，在72小时内输注生理盐水或ACTH（10微克/小时）期间，测量血浆皮质醇（F）、皮质酮（B）和孕酮（P4）。然后将肾上腺分散成分离的细胞，并在体外测定外源性ACTH作用后F、B和P4的分泌量。接受ACTH治疗的胎羊血浆中F和B的浓度较高。F的增加幅度（5至7倍）大于B（2倍），因此在输注第2天和第3天，接受ACTH治疗的胎羊血浆中F:B比值比对照组高2.5倍。输注72小时后，接受ACTH治疗的胎羊肾上腺重量（741±38毫克，±标准误；n = 4）大于对照动物（349±11毫克）。ACTH体内预处理对体外分离的肾上腺细胞F分泌有显著影响。在体外添加ACTH1 - 24（5000皮克/毫升）后，F分泌的平均增加量从对照组的368±235皮克/每50,000个细胞，增加到ACTH体内处理后的64,639±19,875皮克/每50,000个细胞。ACTH体内处理对体外B分泌无显著影响；在体外无论有无ACTH存在，接受ACTH预处理的胎羊细胞中F:B分泌比值均显著更高。ACTH体内处理对体外P4分泌有显著影响。ACTH体内治疗后，体外F:P4分泌比值增加，但B:P4分泌比值无变化。我们得出结论，对胎羊进行ACTH体内治疗会导致胎羊肾上腺功能激活，胎羊肾上腺对ACTH的反应性增加，并使皮质类固醇生物合成向皮质醇方向发展。我们的结果与ACTH治疗后胎羊肾上腺17α - 羟化酶活性增加一致。
