Aberdeen G W, Babischkin J S, Davies W A, Pepe G J, Albrecht E D
Department of Obstetrics/Gynecology/Reproductive Sciences, University of Maryland School of Medicine, Baltimore 21201, USA.
Endocrinology. 1997 Apr;138(4):1634-41. doi: 10.1210/endo.138.4.5079.
We have previously shown a decrease in fetal zone-specific ACTH-stimulable dehydroepiandrosterone formation and an increase in definitive zone-specific cortisol biosynthesis in the baboon fetal adrenal gland in the second half of gestation. Therefore, the fetal and definitive zones seem to develop a divergence in functional capacity with advancing gestation. We have proposed, therefore, that there is a selective decrease in ACTH receptor expression and thus tropic responsivity to ACTH within the fetal zone in the second half of primate pregnancy. The present study examined this possibility and whether corresponding changes occurred in the developmental expression of major components required for steroidogenesis. ACTH receptor messenger RNA (mRNA) levels, determined by in situ hybridization, in the fetal zone of the baboon fetal adrenal were approximately 2-fold greater (P < 0.05) at mid (i.e. day 100) than at late (i.e. day 170) gestation and 3-fold greater (P < 0.01) in the definitive zone than in the fetal zone in late gestation (term = 184 days). Both ACTH receptor and low density lipoprotein receptor mRNA levels, determined by Northern blot in the whole fetal adrenal, also decreased (P < 0.001) by approximately 50%, whereas the mRNA levels for the definitive zone-specific delta5-3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) enzyme required for cortisol biosynthesis increased over 13-fold (P < 0.001) between mid and late gestation. In contrast, mRNA expression of the steroidogenic enzymes P-450 cholesterol side-chain cleavage and 17alpha-hydroxylase/17-20 lyase were unchanged throughout gestation. We conclude that the decrease in ACTH receptor mRNA expression and ACTH-stimulable dehydroepiandrosterone formation in the second half of gestation reflect a decline in functional capacity of the fetal zone, whereas the increase in 3beta-HSD mRNA expression and cortisol production results from the ACTH receptor-mediated development and enhanced functional capacity of the definitive zone.
我们之前已经表明，在狒狒胎儿肾上腺中，妊娠后半期胎儿带特异性促肾上腺皮质激素（ACTH）刺激的脱氢表雄酮生成减少，而成熟带特异性皮质醇生物合成增加。因此，随着妊娠进展，胎儿带和成熟带在功能能力上似乎出现了差异。所以，我们提出，在灵长类动物妊娠后半期，胎儿带内ACTH受体表达存在选择性降低，因而对ACTH的促激素反应性也降低。本研究检验了这种可能性，以及类固醇生成所需主要成分的发育表达是否发生了相应变化。通过原位杂交测定，狒狒胎儿肾上腺胎儿带中ACTH受体信使核糖核酸（mRNA）水平在妊娠中期（即第100天）比晚期（即第170天）大约高2倍（P < 0.05），在妊娠晚期成熟带中的水平比胎儿带高3倍（P < 0.01）（足月为184天）。通过Northern印迹法在整个胎儿肾上腺中测定，ACTH受体和低密度脂蛋白受体mRNA水平也下降了（P < 0.001）约50%，而皮质醇生物合成所需的成熟带特异性δ5-3β-羟基类固醇脱氢酶/异构酶（3β-HSD）的mRNA水平在妊娠中期和晚期之间增加了超过13倍（P < 0.001）。相比之下，类固醇生成酶P-450胆固醇侧链裂解酶和17α-羟化酶/17,20裂解酶的mRNA表达在整个妊娠期间没有变化。我们得出结论，妊娠后半期ACTH受体mRNA表达和ACTH刺激的脱氢表雄酮生成减少反映了胎儿带功能能力的下降，而3β-HSD mRNA表达和皮质醇产生的增加是由于ACTH受体介导的成熟带发育和功能能力增强所致。
