Myers D A, McDonald T J, Nathanielsz P W
Laboratory for Pregnancy and Newborn Research, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853-6401.
Endocrinology. 1992 Sep;131(3):1329-35. doi: 10.1210/endo.131.3.1505467.
The preterm rise in the concentration of ovine fetal plasma cortisol that initiates the events of parturition in sheep commences at approximately 125 days of gestational age (dGA; term = approximately 147 dGA). Concurrent with the rise in fetal plasma cortisol, adrenocortical steroid hydroxylase enzyme activity increases. The purpose of this study was 1) to quantitate changes in levels of mRNA for the steroid hydroxylases, 17-hydroxylase cytochrome P450 (P450(17)alpha), side-chain cleavage cytochrome P450 (P450scc), 11 beta-hydroxylase cytochrome P450 (P450(11)beta), and C21-hydroxylase cytochrome P450 (P450C21); and 2) examine the role of the fetal paraventricular nucleus (PVN) in the onset of adrenocortical steroid hydroxylase mRNA expression. Unperturbed fetuses were collected by cesarian section under halothane anesthesia at 105 (n = 4), 120 (n = 4), 126-128 (n = 4), and 136 dGA (n = 3); neonatal animals were collected within 2 h after birth. To examine the role of the fetal PVN in regulation of adrenocortical steroid hydroxylase mRNA expression, ovine fetuses were stereotaxically implanted bilaterally 2 mm lateral to the fetal PVN at 105-107 dGA with either cholesterol (n = 4) or dexamethasone (DEX; n = 3). Implanted fetuses were collected by cesarian section under halothane anesthesia at 126-128 dGA. mRNA for both cytochrome P450(17)alpha and P450scc declined 3-fold from 105 to 120 dGA (P less than or equal to 0.05), and then increased by 126-128 dGA compared to that on 120 dGA (P less than or equal to 0.05) and continued to increase through term. Cytochrome P450C21 increased at 126-128 dGA compared to that on 105 and 120 dGA (P less than or equal to 0.05) and remained elevated through term. Three distinct transcripts [approximately 6.2, 4.2, and 2.5 kilobases (kb)] were observed for cytochrome P450(11)beta; the 4.2-kb transcript was predominant. While total message for P450(11)beta declined over increasing gestational age, no differences were noted for the 4.2-kb transcript until after birth, when levels significantly declined (P less than or equal to 0.025). Placement of DEX adjacent to the fetal PVN prevented reemergence of expression of mRNA for P450(17)alpha and P450scc at 126-128 dGA, but had no effect on mRNA for P450C21 or P45011 beta. We conclude that mRNA for P450(17)alpha and P450scc undergoes a decline in expression concurrent with the previously described period of adrenal hyporesponsiveness from 105-126 dGA, followed by an increase in mRNA that accompanies the preterm rise in fetal plasma cortisol.(ABSTRACT TRUNCATED AT 400 WORDS)
绵羊胎儿血浆皮质醇浓度的早产期升高引发了绵羊分娩过程，这一过程大约在妊娠125天（dGA；足月约为147 dGA）开始。与胎儿血浆皮质醇升高同时，肾上腺皮质类固醇羟化酶活性增加。本研究的目的是：1）定量类固醇羟化酶17 - 羟化酶细胞色素P450（P450(17)α）、侧链裂解细胞色素P450（P450scc）、11β - 羟化酶细胞色素P450（P450(11)β）和C21 - 羟化酶细胞色素P450（P450C21）的mRNA水平变化；2）研究胎儿室旁核（PVN）在肾上腺皮质类固醇羟化酶mRNA表达起始中的作用。在氟烷麻醉下，于妊娠105天（n = 4）、120天（n = 4）、126 - 128天（n = 4）和136天（n = 3）通过剖宫产收集未受干扰的胎儿；新生动物在出生后2小时内收集。为研究胎儿PVN在肾上腺皮质类固醇羟化酶mRNA表达调节中的作用，在妊娠105 - 107天对绵羊胎儿双侧立体定位植入到胎儿PVN外侧2 mm处，植入胆固醇（n = 4）或地塞米松（DEX；n = 3）。在氟烷麻醉下，于妊娠126 - 128天通过剖宫产收集植入胎儿。从105天到120天，细胞色素P450(17)α和P450scc的mRNA均下降了3倍（P≤0.05），然后与120天时相比，在126 - 128天时增加（P≤0.05），并持续增加直至足月。与105天和120天时相比，细胞色素P450C21在126 - 128天时增加（P≤0.05），并在足月时保持升高。观察到细胞色素P450(11)β有三种不同的转录本[约6.2、4.2和2.5千碱基（kb）]；4.2 - kb转录本占主导。虽然P450(11)β的总信息随着胎龄增加而下降，但直到出生后4.2 - kb转录本才出现差异且水平显著下降（P≤0.025）。在胎儿PVN附近放置DEX可阻止126 - 128天时P450(17)α和P450scc的mRNA表达再次出现，但对P450C21或P450(11)β的mRNA无影响。我们得出结论，P450(17)α和P450scc的mRNA表达在与之前描述的105 - 126天肾上腺反应性降低期同时下降，随后mRNA增加，这与胎儿血浆皮质醇的早产期升高相伴。（摘要截断于400字）
