Challis J R, Brooks A N
Lawson Research Institute, St. Joseph's Health Centre, London, Ontario, Canada.
Endocr Rev. 1989 May;10(2):182-204. doi: 10.1210/edrv-10-2-182.
The progressive rise in the concentration of cortisol in the plasma of fetal sheep during late pregnancy arises from the sequential maturation of the fetal HPA axis. In addition, cortisol itself occupies a central role in accelerating this process through a series of feed-forward mechanisms. Before days 100-110 of pregnancy AVP appears to predominate over CRH as the major corticotropin-releasing factor in the fetus. Pituitary responsiveness to CRH increases progressively after day 100, and precedes maturation of fetal adrenal responsiveness to endogenous or exogenous ACTH. Cortisol accelerates the increase in the ratio of adult-fetal corticotropes in the fetal pituitary. In addition, cortisol modulates the mechanism by which ACTH activates fetal adrenal function, possibly through an action at the level of the ACTH receptor. Cortisol appears also to mediate the rise in fetal plasma CBG concentrations during late pregnancy, and may thereby alter the efficacy of the negative feedback process. In women, cortisol acts on the placenta to promote rather than to inhibit CRH output. CRH from the placenta may reach significant concentrations in the fetal circulation and augment the drive to fetal ACTH release. It may also act in a paracrine fashion to promote placental POMC gene expression. The importance of placental CRF and ACTH in the sheep is not yet apparent. These feed-forward loops establish a series of positive cascades that ensure concurrent rises in plasma ACTH and cortisol in the fetal circulation during late pregnancy. We suggest that this sequence leads to, and is broken by, the process of birth.
妊娠晚期绵羊胎儿血浆中皮质醇浓度的逐渐升高源于胎儿下丘脑-垂体-肾上腺（HPA）轴的顺序成熟。此外，皮质醇本身通过一系列前馈机制在加速这一过程中发挥核心作用。在妊娠100 - 110天之前，血管加压素（AVP）似乎比促肾上腺皮质激素释放激素（CRH）更占主导地位，是胎儿主要的促肾上腺皮质激素释放因子。垂体对CRH的反应性在100天后逐渐增加，并先于胎儿肾上腺对内源性或外源性促肾上腺皮质激素（ACTH）反应性的成熟。皮质醇加速了胎儿垂体中成年型与胎儿型促肾上腺皮质激素细胞比例的增加。此外，皮质醇可能通过作用于ACTH受体水平来调节ACTH激活胎儿肾上腺功能的机制。皮质醇似乎还介导了妊娠晚期胎儿血浆中皮质类固醇结合球蛋白（CBG）浓度的升高，从而可能改变负反馈过程的效力。在女性中，皮质醇作用于胎盘以促进而非抑制CRH的分泌。来自胎盘的CRH可能在胎儿循环中达到显著浓度，并增强对胎儿ACTH释放的驱动。它也可能以旁分泌方式促进胎盘阿黑皮素原（POMC）基因的表达。胎盘促肾上腺皮质激素释放因子（CRF）和ACTH在绵羊中的重要性尚不明显。这些前馈回路建立了一系列正反馈级联反应，确保妊娠晚期胎儿循环中血浆ACTH和皮质醇同时升高。我们认为这一序列导致了分娩过程，并在分娩时被打破。
