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 Jul;131(1):305-10. doi: 10.1210/endo.131.1.1612010.
Fetal adrenal steroid hydroxylase activity and messenger RNA (mRNA) expression increases concurrent with the preterm rise in fetal plasma cortisol during late gestation in sheep. By placing bilateral lesions of the fetal paraventricular nuclei (PVN) we have previously demonstrated that the fetal PVN is necessary for the initiation of parturition, the late gestation preparturient increase in fetal plasma cortisol and ACTH, and ACTH secretion in response to fetal hypoxemia and hypotension. The purpose of this study was to determine the role of the fetal PVN in the late gestation increase in expression of mRNA for 17 alpha-hydroxylase (P-450(17)alpha), side-chain cleavage (P-450SCC), 11 beta-hydroxylase (P-450(11)beta), 21 hydroxylase (P-450C21), and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in the fetal adrenal. Ovine fetuses were subjected to bilateral lesions of the PVN (Lx; n = 4) or sham lesions (Sh; n = 4) at 118-122 days gestational age (dGA). Lx fetuses were recovered by cesarean section at greater than or equal to 157 dGA; Sh fetuses were recovered immediately postbirth at normal term (146.5 +/- 0.9 dGA). In addition, uninstrumented fetuses were obtained at 145-147 dGA by cesarean section (n = 3). RNA obtained from individual fetal adrenals was subjected to Northern analysis. Lx of the fetal PVN decreased (P less than or equal to 0.05) mRNA for P-450(17)alpha and P-450SCC but did not affect adrenocortical mRNA for P-450C21, P-450(11)beta, or 3 beta-HSD compared to Sh. To determine if the differences observed between Lx and Sh for P-450(17)alpha and P-450SCC mRNA were due to the process of labor, we compared uninstrumented 145-147 dGA to Sh. No differences in adrenal mRNA content were observed for P-450(17)alpha or P-450SCC between these groups. We conclude that in late gestation fetal sheep an intact fetal PVN is necessary for normal gene expression of adrenocortical P-450(17)alpha and P-450SCC while P-450(11)beta, P-450C21, and 3 beta-HSD may be primarily regulated by factors not dependent upon a functional PVN.
在绵羊妊娠后期，胎儿肾上腺类固醇羟化酶活性和信使核糖核酸（mRNA）表达随着胎儿血浆皮质醇在早产前的升高而增加。通过对胎儿室旁核（PVN）进行双侧损伤，我们先前已经证明胎儿PVN对于分娩的启动、妊娠后期胎儿血浆皮质醇和促肾上腺皮质激素（ACTH）的产前增加以及对胎儿低氧血症和低血压的ACTH分泌是必需的。本研究的目的是确定胎儿PVN在妊娠后期胎儿肾上腺中17α-羟化酶（P-450(17)α）、侧链裂解酶（P-450SCC）、11β-羟化酶（P-450(11)β）、21-羟化酶（P-450C21）和3β-羟类固醇脱氢酶（3β-HSD）mRNA表达增加中的作用。在妊娠118 - 122天（dGA）时，对绵羊胎儿进行PVN双侧损伤（Lx；n = 4）或假损伤（Sh；n = 4）。Lx组胎儿在大于或等于157 dGA时通过剖宫产取出；Sh组胎儿在足月正常分娩后立即取出（146.5±0.9 dGA）。此外，在145 - 147 dGA时通过剖宫产获取未进行手术操作的胎儿（n = 3）。从单个胎儿肾上腺获得的RNA进行Northern分析。与Sh组相比，胎儿PVN的损伤使P-450(17)α和P-450SCC的mRNA减少（P≤0.05），但不影响肾上腺皮质中P-450C21、P-450(11)β或3β-HSD的mRNA。为了确定Lx组和Sh组在P-450(17)α和P-450SCC mRNA上观察到的差异是否是由于分娩过程导致的，我们将未进行手术操作的145 - 147 dGA胎儿与Sh组进行比较。这些组之间在P-450(17)α或P-450SCC的肾上腺mRNA含量上未观察到差异。我们得出结论，在妊娠后期的绵羊胎儿中，完整的胎儿PVN对于肾上腺皮质P-450(17)α和P-450SCC的正常基因表达是必需的，而P-450(11)β、P-450C21和3β-HSD可能主要受不依赖于功能性PVN的因素调节。
