Ross J T, Phillips I D, Owens J A, McMillen I C
Department of Physiology, Adelaide University, Australia.
J Neuroendocrinol. 1997 Sep;9(9):663-8. doi: 10.1046/j.1365-2826.1997.00623.x.
We have investigated the effects of a 5 day infusion of cortisol into fetal sheep, in which the hypothalamus and pituitary were surgically disconnected (HPD), on fetal pituitary-adrenal function. Fetal HPD and vascular catheterization were carried out at between 104 and 124 days gestation. Cortisol was administered (3.5 mg 24 h-1) for 120 h between 134 and 140 days (HPD + F group; n = 5) and saline was administered during the same gestational age range to HPD (HPD group; n = 12) and intact fetal sheep (Intact group; n = 6). Cortisol infusion into the HPD fetal sheep did not suppress the mRNA levels for Proopiomelanocortin (POMC) in the fetal anterior pituitary at 139/140 days gestation (POMC mRNA: 18S rRNA: Intact 0.40 +/- 0.05; HPD 0.56 +/- 0.07; HPD + F 0.49 +/- 0.07). Similarly, there was no significant effect of either HPD or cortisol infusion on the plasma concentrations of immunoreactive (ir) ACTH or ACTH(1-39). The adrenal: fetal body weight ratio was significantly higher, however, in the HPD + F (88.4 +/- 8.7 mg kg-1) and Intact groups (84.1 +/- 5.6 mg kg-1) when compared with the HPD fetal sheep (63.7 +/- 5.4 mg kg-1). The ratio of total IGF-II mRNA: 18S rRNA was similar in the adrenals of the Intact (0.48 +/- 0.09), HPD (0.78 +/- 0.09) and HPD + F (0.71 +/- 0.11) groups. The ratios of CYPIIA1, 3 beta-HSD and CYP21A1 mRNA: 18S rRNA were significantly lower in adrenals from the HPD group when compared to those in the Intact group and were not restored to normal by cortisol infusion. We have therefore demonstrated that cortisol does not act directly at the fetal pituitary to suppress POMC synthesis or ACTH secretion in late gestation. Cortisol does, however, stimulate fetal adrenal growth after HPD in the absence of any effects on adrenal IGF-II or steroidogenic enzyme mRNA levels. The data provide evidence that an intact hypothalamic-pituitary axis and cortisol each play an important role in the stimulation of adrenal growth and steroidogenesis which occurs during the last 10-15 days of gestation in the sheep.
我们研究了对妊娠绵羊胎儿连续5天输注皮质醇对其垂体-肾上腺功能的影响，这些胎儿的下丘脑和垂体已通过手术切断（HPD）。在妊娠104至124天之间进行胎儿HPD手术及血管插管。在妊娠134至140天之间，对HPD + F组（n = 5）的胎儿连续120小时给予皮质醇（3.5 mg 24 h-1），在相同妊娠年龄范围内，对HPD组（n = 12）和完整胎儿绵羊组（完整组；n = 6）给予生理盐水。在妊娠139/140天时，向HPD胎儿绵羊输注皮质醇并未抑制胎儿垂体中阿黑皮素原（POMC）的mRNA水平（POMC mRNA：18S rRNA：完整组0.40 +/- 0.05；HPD组0.56 +/- 0.07；HPD + F组0.49 +/- 0.07）。同样，HPD或皮质醇输注对免疫反应性（ir）促肾上腺皮质激素（ACTH）或ACTH(1-39)的血浆浓度均无显著影响。然而，与HPD胎儿绵羊（63.7 +/- 5.4 mg kg-1）相比，HPD + F组（88.4 +/- 8.7 mg kg-1）和完整组（84.1 +/- 5.6 mg kg-1）的肾上腺与胎儿体重之比显著更高。完整组（0.48 +/- 0.09）、HPD组（0.78 +/- 0.09）和HPD + F组（0.71 +/- 0.11）肾上腺中总胰岛素样生长因子-II（IGF-II）mRNA与18S rRNA的比值相似。与完整组相比，HPD组肾上腺中细胞色素P450 11A1（CYP11A1）、3β-羟基类固醇脱氢酶（3β-HSD）和细胞色素P450 21A2（CYP21A2）mRNA与18S rRNA的比值显著更低，且皮质醇输注并未使其恢复正常。因此，我们证明了在妊娠晚期，皮质醇并非直接作用于胎儿垂体以抑制POMC合成或ACTH分泌。然而，在HPD后，皮质醇确实刺激了胎儿肾上腺生长，且对肾上腺IGF-II或类固醇生成酶mRNA水平无任何影响。这些数据表明，完整的下丘脑-垂体轴和皮质醇在刺激绵羊妊娠最后10 - 15天期间发生的肾上腺生长和类固醇生成中均发挥重要作用。
