Simmonds P J, Phillips I D, Poore K R, Coghill I D, Young I R, Canny B J
Department of Physiology, Monash University, PO Box 13F, Clayton, Victoria 3800, Australia.
J Endocrinol. 2001 Mar;168(3):475-85. doi: 10.1677/joe.0.1680475.
To further understand the relative roles of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins that are essential for adrenal development, we investigated the effects of, first, an ACTH infusion and labour in intact fetuses and, secondly, the effect of an ACTH infusion to fetuses with and without a pituitary gland, on the relative abundance of the mRNA encoding for the ACTH receptor (MC2R), steroidogenic factor 1 (SF-1), cholesterol side-chain cleavage enzyme (P450(scc)), 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17alpha-hydroxylase (P450(C17)) in the fetal adrenal gland. ACTH(1-24) infusion (14.7 pmol/kg per h) to intact fetuses was without effect on the abundance of mRNA encoding MC2R and SF-1, irrespective of whether the infusion was given for 18 (115-132 days of gestation) or 32 days (115 days to term (147 days of gestation)). Hypophysectomy (HX) did not alter the expression of MC2R mRNA; however, the abundance of SF-1 mRNA fell by approximately 50% following the removal of the pituitary gland. ACTH(1-24) infusion to HX fetuses failed to restore levels of SF-1 mRNA to that seen in intact animals. P450(scc) and 3betaHSD mRNAs were increased by ACTH(1-24) infusion for 18 days in intact animals, although no effects of the infusion were seen on P450(C17) mRNA levels. For all three of these mRNAs, there was a significant increase in their abundance between 132 days of gestation and term in intact fetuses. By term, ACTH(1-24) infusion was without any additional effect on their abundance. HX decreased the expression of P450(scc), 3betaHSD and P450(C17) mRNAs, while ACTH(1-24) infusion to HX fetuses increased the expression of these mRNAs to levels seen in intact animals. There were significant correlations between the abundance of the mRNA for P450(scc), 3betaHSD and P450(C17), but not MC2R and SF-1, and premortem plasma cortisol concentrations. These results emphasise the importance of the pituitary gland and ACTH in the regulation of the enzymes involved in adrenal steroidogenesis. Factors in addition to ACTH may also play some role, as the infusion was not always effective in increasing the abundance of the mRNAs. Surprisingly, the mRNA for MC2R and SF-1 did not appear to be regulated by ACTH in the late-gestation ovine fetus, though a pituitary-dependent factor may be involved in the regulation of SF-1 mRNA abundance.
为了进一步了解垂体和促肾上腺皮质激素（ACTH）在调节对肾上腺发育至关重要的蛋白质编码mRNA中的相对作用，我们进行了如下研究：首先，对完整胎儿进行ACTH输注和分娩，观察其影响；其次，对有或无垂体的胎儿进行ACTH输注，观察其对胎儿肾上腺中ACTH受体（MC2R）、类固醇生成因子1（SF-1）、胆固醇侧链裂解酶（P450(scc)）、3β-羟基类固醇脱氢酶（3βHSD）和17α-羟化酶（P450(C17)）编码mRNA相对丰度的影响。对完整胎儿输注ACTH(1 - 24)（14.7 pmol/kg每小时），无论输注18天（妊娠115 - 132天）还是32天（妊娠115天至足月（147天）），均对MC2R和SF-1编码mRNA的丰度无影响。垂体切除（HX）未改变MC2R mRNA的表达；然而，切除垂体后SF-1 mRNA的丰度下降了约50%。对HX胎儿输注ACTH(1 - 24)未能将SF-1 mRNA水平恢复到完整动物的水平。在完整动物中，输注ACTH(1 - 24) 18天可使P450(scc)和3βHSD mRNA增加，尽管输注对P450(C17) mRNA水平无影响。对于所有这三种mRNA，在完整胎儿中，从妊娠132天到足月，其丰度显著增加。到足月时，输注ACTH(1 - 24)对其丰度无任何额外影响。HX降低了P450(scc)、3βHSD和P450(C17) mRNA的表达，而对HX胎儿输注ACTH(1 - 24)可使这些mRNA的表达增加到完整动物的水平。P450(scc)、3βHSD和P450(C17) mRNA的丰度与死前血浆皮质醇浓度之间存在显著相关性，但MC2R和SF-1 mRNA与死前血浆皮质醇浓度之间无显著相关性。这些结果强调了垂体和ACTH在调节肾上腺类固醇生成相关酶中的重要性。除ACTH外的其他因素可能也起一定作用，因为输注并不总是能有效增加mRNA的丰度。令人惊讶的是，在妊娠晚期绵羊胎儿中，MC2R和SF-1 mRNA似乎不受ACTH调节，尽管一种垂体依赖性因子可能参与SF-1 mRNA丰度的调节。
