Casey M L, Guerami A, Winkel C A, MacDonald P C
J Steroid Biochem. 1984 Jan;20(1):237-43. doi: 10.1016/0022-4731(84)90210-3.
DOC and DOC-SO4, which are present in large amounts in the blood of pregnant women, are derived from sources other than maternal adrenal. Other investigators demonstrated that treatment of near-term pregnant women with ACTH or dexamethasone did not cause alterations in the blood levels of DOC. To define the source(s) of DOC and DOC-SO4 in plasma of pregnant women, we evaluated the conversion of plasma progesterone (P) to DOC in extraadrenal sites. DOC is formed from plasma P and, provided that the pregnancy is one characterized by the usual large production of estrogen, DOC production in a given woman is proportional to the level of P in plasma. Unlike other steroid conversions or interconversions, however, the fractional conversion of P to DOC among apparently normal persons varied widely 0.011 +/- 0.003 (mean +/- SEM, n = 40, range = 0.001 to 0.030). In women pregnant with a normal living fetus, the product of the production rate of P and the fractional conversion of P to DOC is sufficient to account for the majority of DOC produced in the mother. There may be a second source of DOC, i.e. the transfer of DOC from the fetal to the maternal compartment in a manner that involves (a) direct transfer of DOC by way of trophoblast and (b) by desulfurylation of DOC-SO4 from fetal umbilical arterial plasma in trophoblast and thence transfer of DOC liberated in trophoblast to the maternal compartment. Presently, it is clear that DOC-SO4 in blood of pregnant women is not derived from plasma DOC; and there is little or no evidence in support of the proposition that DOC-SO4 (as a sulfoconjugate) is transferred from the fetal to the maternal compartment because of placental hydrolysis to DOC. Among the extraadrenal tissue sites identified as those in which 21-hydroxylation of plasma P could be effected are some also believed to be tissue sites of mineralocorticosteroid action, viz, kidney, aorta, thymus, and spleen. Quantitatively, the origin of DOC in the fetus is not as clear as in the maternal compartment; yet, many tissues of the fetus have been identified in which both steroid 21-hydroxylase and 21-hydroxysteroid sulfotransferase activity are present. Thus, in the human fetus, extraadrenal as well as adrenal production of DOC and DOC-SO4 are possible.
在孕妇血液中大量存在的双氢皮质醇(DOC)和硫酸双氢皮质醇(DOC-SO4)并非源自母体肾上腺。其他研究人员表明,对足月孕妇使用促肾上腺皮质激素(ACTH)或地塞米松治疗并不会导致血液中DOC水平发生改变。为了确定孕妇血浆中DOC和DOC-SO4的来源,我们评估了肾上腺外部位血浆孕酮(P)向DOC的转化情况。DOC由血浆P形成,并且如果妊娠具有通常大量产生雌激素的特征,那么特定女性体内DOC的产生量与血浆中P的水平成正比。然而,与其他类固醇转化或相互转化不同的是,在明显正常的人群中,P向DOC的分数转化率差异很大,为0.011±0.003(平均值±标准误,n = 40,范围为0.001至0.030)。在怀有正常存活胎儿的女性中,P的产生速率与P向DOC的分数转化率的乘积足以解释母体中产生的大部分DOC。可能存在DOC的第二个来源,即DOC以以下方式从胎儿向母体 compartment转移:(a)通过滋养层直接转移DOC,以及(b)通过滋养层中胎儿脐动脉血浆中的DOC-SO4脱硫,然后将滋养层中释放的DOC转移到母体 compartment。目前,很明显孕妇血液中的DOC-SO4并非源自血浆DOC;并且几乎没有证据支持DOC-SO4(作为硫酸共轭物)因胎盘水解为DOC而从胎儿转移到母体 compartment这一观点。在被确定为能够实现血浆P 21-羟化的肾上腺外组织部位中,有些也被认为是盐皮质激素作用的组织部位,即肾脏、主动脉、胸腺和脾脏。从数量上看,胎儿体内DOC的来源不如母体 compartment中那么清晰;然而,已经在胎儿的许多组织中鉴定出同时存在类固醇21-羟化酶和21-羟类固醇硫酸转移酶活性。因此,在人类胎儿中,肾上腺外以及肾上腺产生DOC和DOC-SO4都是可能的。