Lund J, Mason J I, Simpson E R, Waterman M R
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
Endocr Res. 1989;15(1-2):17-29. doi: 10.1080/07435808909039086.
Among the multifactorial aspects of regulation of steroid hydroxylase gene expression, it is the developmental process which leads to imprinting of expression of particular steroid hydroxylases in specific cell types. We have begun to investigate the ontogeny of steroidogenesis in fetal bovine tissues. Expression of most steroid hydroxylases and related enzymes is detectable in adrenals of the smallest fetuses studied and continues throughout fetal life. Like the other steroid hydroxylases, P-450(17)alpha is detectable in the earliest fetal adrenals studied. However, following an increase in expression, P-450(17)alpha disappears from the fetal adrenal by 100 days gestational age and remains absent until about 230 days gestational age. The absence of P-450(17)alpha is correlated with the absence of cortisol in the fetal adrenal and the absence of ACTH in fetal plasma. Thus expression of P-450(17)alpha in bovine fetal adrenal appears to be strictly dependent on cAMP while expression of other steroid hydroxylases appears to involve both cAMP-dependent and cAMP-independent mechanisms. Furthermore, P-450(17)alpha is expressed in fetal testis at gestational times when it is absent in fetal adrenal. We have begun to examine binding of nuclear proteins from adrenals of various gestational ages to the 5'-flanking region of the bovine P-450(17)alpha gene. Preliminary evidence indicates the presence of a protein in nuclei of fetal adrenals not expressing P-450(17)alpha that is not present in fetal adrenals of other gestational ages.
在类固醇羟化酶基因表达调控的多因素方面，发育过程导致特定类固醇羟化酶在特定细胞类型中的表达印记。我们已开始研究胎牛组织中类固醇生成的个体发生。在研究的最小胎儿的肾上腺中可检测到大多数类固醇羟化酶和相关酶的表达，并且在整个胎儿期持续存在。与其他类固醇羟化酶一样，在最早研究的胎儿肾上腺中可检测到P-450(17)α。然而，在表达增加后，P-450(17)α在妊娠100天时从胎儿肾上腺中消失，直到妊娠约230天时仍未出现。P-450(17)α的缺失与胎儿肾上腺中皮质醇的缺失以及胎儿血浆中促肾上腺皮质激素的缺失相关。因此，牛胎儿肾上腺中P-450(17)α的表达似乎严格依赖于cAMP，而其他类固醇羟化酶的表达似乎涉及cAMP依赖性和cAMP非依赖性机制。此外，P-450(17)α在胎儿肾上腺中不存在的妊娠时期在胎儿睾丸中表达。我们已开始研究来自不同妊娠年龄肾上腺的核蛋白与牛P-450(17)α基因5'-侧翼区域的结合。初步证据表明，在不表达P-450(17)α的胎儿肾上腺细胞核中存在一种蛋白质，而在其他妊娠年龄的胎儿肾上腺中不存在这种蛋白质。
