Rose J C, Turner C S, Ray D, Rawashdeh N
Department of Physiology, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103.
Endocrinology. 1988 Sep;123(3):1307-13. doi: 10.1210/endo-123-3-1307.
To ascertain if reductions in fetal plasma cortisol cause increases in fetal plasma ACTH, we treated pregnant ewes or their fetuses with aminoglutethimide (10 mg/kg BW) and metyrapone (20 mg/kg BW) and measured the hormonal responses with RIAs. When given to fetuses (n = 9) at 0.90 +/- 0.01 gestation (term-145 days), the steroid synthesis inhibitors reduced fetal plasma cortisol from 35.1 +/- 11.9 to 18.5 +/- 6.2 ng/ml (P less than 0.01) and plasma ACTH increased from 37 +/- 7 to 189 +/- 74 pg/ml (P less than 0.02). Thus, late in gestation cortisol from the fetal adrenal suppresses basal fetal ACTH secretion. Blockade of steroid biosynthesis in pregnant ewes carrying intact fetuses at 0.76 +/- 0.02 gestation (n = 11) or adrenalectomized fetuses at 0.81 +/- 0.01 gestation (n = 6) also reduced cortisol and increased ACTH in fetal plasma. In intact fetuses cortisol declined from 9.4 +/- 2.0 to 3.6 +/- 0.9 ng/ml (P less than 0.05), and ACTH increased from 46 +/- 8 to 183 +/- 67 (P less than 0.01); cortisol declined in adrenalectomized fetuses from 2.1 +/- 0.4 to 1.1 +/- 0.3 ng/ml (P less than 0.01), and ACTH increased from 106 +/- 13 to 400 +/- 104 pg/ml (P less than 0.01). Cortisol infusions into intact and adrenalectomized fetuses prevented both the decline in steroid concentration caused by the biosynthesis inhibitors given to the ewe and the increase in fetal plasma ACTH concentration. These data indicate that reductions in plasma cortisol in adrenalectomized fetuses or intact fetuses at a time in development when the fetal adrenal produces little cortisol cause compensatory increases in fetal plasma ACTH concentration. The simplest explanation for these observations is that from approximately 0.70 gestation, basal fetal ACTH secretion is tonically inhibited by cortisol circulating in fetal plasma. This cortisol can originate from sources other than the fetal adrenal.
为了确定胎儿血浆皮质醇的降低是否会导致胎儿血浆促肾上腺皮质激素（ACTH）升高，我们用氨鲁米特（10mg/kg体重）和甲吡酮（20mg/kg体重）处理怀孕母羊或其胎儿，并通过放射免疫分析法（RIAs）测量激素反应。当在妊娠0.90±0.01（足月为145天）时给予胎儿（n = 9），这些类固醇合成抑制剂使胎儿血浆皮质醇从35.1±11.9降至18.5±6.2ng/ml（P＜0.01），血浆ACTH从37±7升至189±74pg/ml（P＜0.02）。因此，在妊娠后期，胎儿肾上腺分泌的皮质醇抑制胎儿ACTH的基础分泌。在妊娠0.76±0.02（n = 11）时携带完整胎儿的怀孕母羊或在妊娠0.81±0.01（n = 6）时携带肾上腺切除胎儿的怀孕母羊中，阻断类固醇生物合成也降低了胎儿血浆中的皮质醇并增加了ACTH。在完整胎儿中，皮质醇从9.4±2.0降至3.6±0.9ng/ml（P＜0.05），ACTH从46±8升至183±67（P＜0.01）；在肾上腺切除胎儿中，皮质醇从2.1±0.4降至1.1±0.3ng/ml（P＜0.01），ACTH从106±13升至400±104pg/ml（P＜0.01）。向完整胎儿和肾上腺切除胎儿输注皮质醇可防止因给母羊使用生物合成抑制剂而导致的类固醇浓度下降以及胎儿血浆ACTH浓度升高。这些数据表明，在胎儿肾上腺产生很少皮质醇的发育阶段，肾上腺切除胎儿或完整胎儿血浆皮质醇的降低会导致胎儿血浆ACTH浓度的代偿性升高。对这些观察结果最简单的解释是，从大约妊娠0.70开始，胎儿ACTH的基础分泌受到胎儿血浆中循环皮质醇的持续抑制。这种皮质醇可能来源于胎儿肾上腺以外的其他来源。
