Modulation of adrenocorticotropin-stimulated baboon fetal adrenal dehydroepiandrosterone formation in vitro by estrogen at mid- and late gestation.
Modulation of adrenocorticotropin-stimulated baboon fetal adrenal dehydroepiandrosterone formation in vitro by estrogen at mid- and late gestation.
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DOI：
10.1210/endo-126-6-3083
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发表时间：
1990-06
期刊：
影响因子：
4.8
通讯作者：
E. Albrecht;Michael C. Henson;Margaret L. Walker;G. Pepe
中科院分区：
文献类型：
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作者：
E. Albrecht;Michael C. Henson;Margaret L. Walker;G. Pepe
我们报道了狒狒胎儿肾上腺在妊娠中期对促肾上腺皮质激素（ACTH）刺激脱氢表雄酮（DHA）的形成被雌激素抑制。由于胎儿肾上腺的调节随着妊娠的进展而变化，雌激素对胎儿肾上腺类固醇生成的作用也可能取决于胎儿肾上腺的成熟程度。我们在本研究中通过确定 ACTH 和雌激素对从妊娠中后期狒狒以及在整个妊娠后期施用抗雌激素 MER-25 的动物中获得的胎儿的肾上腺细胞 DHA 形成的影响来检验这种可能性。由于低密度脂蛋白 (LDL) 为胎儿肾上腺提供底物，因此我们还确定了雌激素的作用是否由 LDL 摄取介导。未处理动物在妊娠第 100 天（妊娠中期；n = 7）和第 170 天（妊娠晚期；n = 6；足月，第 184 天）狒狒胎儿的肾上腺被切除，母亲在第 140-170 天接受 MER-25（25 mg/kg BW.day；n = 7）治疗的母亲的胎儿在第 170 天被切除肾上腺。将细胞用0.2％胶原酶分散并在4ml培养基199(含有10nM ACTH、10(-6)M雌二醇和/或500微克LDL)中于37℃温育3小时。通过RIA测定DHA向培养基的分泌。妊娠中期，平均 (+/- SE) 基础 DHA 形成（纳克每 10(5) 细胞/3 小时）为 5.8 +/- 2.1，ACTH 使 DHA 增加（P 小于 0.01）至 20.0 +/- 5.9。虽然单独使用雌二醇没有效果，但雌二醇可以阻止使用 ACTH 获得的 DHA 的增加。妊娠晚期肾上腺产生的基础 DHA（0.7 +/- 0.3 ng/10(5) 细胞）低于妊娠中期（P 小于 0.01）。在雌二醇存在 (2.0 +/- 0.4) 或不存在 (1.7 +/- 0.4) 的情况下，ACTH 会以类似的方式增加近期 DHA（P 小于 0.01）。因此，与第100天相比，雌激素在第170天并没有减弱ACTH对肾上腺细胞的作用。在第170天从经MER-25处理的狒狒获得的胎儿肾上腺细胞中，DHA形成（1.4+/-0.6ng/10（5）细胞）相对增加（P小于0.05）至2.4+/-0.2，并且在不存在或存在雌二醇的情况下，ACTH 为 3.0 +/- 0.5 ng/10(5) 个细胞。因此，ACTH 在通过子宫内暴露于抗雌激素的胎儿的肾上腺细胞增强 DHA 方面仍然有效。 LDL 和 ACTH 加 LDL 使妊娠中期肾上腺形成的 DHA 分别增加（P 小于 0.05）至 15.4 +/- 4.8 和 27.4 +/- 7.5 ng/10(5) 细胞。（摘要截断为 400 字）
We have reported that ACTH stimulation of dehydroepiandrosterone (DHA) formation by the baboon fetal adrenal at midgestation was suppressed by estrogen. Because fetal adrenal regulation changes with advancing gestation, the action of estrogen on fetal adrenal steroidogenesis may also be dependent on the degree of fetal adrenal maturation. We examined this possibility in the present study by determining the effects of ACTH and estrogen on DHA formation by adrenal cells of fetuses obtained from baboons at mid- and late gestation and from animals administered the antiestrogen MER-25 throughout late gestation. Because low density lipoprotein (LDL) provides substrate for the fetal adrenal, we also determined whether the effect of estrogen was mediated by LDL uptake. Adrenals were removed from baboon fetuses on day 100 (midgestation; n = 7) and day 170 (late gestation; n = 6; term, day 184) of gestation from untreated animals and on day 170 from fetuses whose mothers were treated with MER-25 on days 140-170 (25 mg/kg BW.day; n = 7). Cells were dispersed with 0.2% collagenase and incubated at 37 C for 3 h in 4 ml medium 199 with 10 nM ACTH, 10(-6) M estradiol and/or 500 micrograms LDL. The secretion of DHA into medium was determined by RIA. At midgestation, mean (+/- SE) basal DHA formation (nanograms per 10(5) cells/3 h) was 5.8 +/- 2.1, and DHA was increased (P less than 0.01) by ACTH to 20.0 +/- 5.9. Although estradiol alone had no effect, estradiol prevented the increase in DHA obtained with ACTH. Basal DHA production by adrenals of late gestation (0.7 +/- 0.3 ng/10(5) cells) was lower (P less than 0.01) than at midgestation. ACTH increased (P less than 0.01) DHA in a comparable manner near term in the presence (2.0 +/- 0.4) or absence (1.7 +/- 0.4) of estradiol. Thus, in contrast to day 100, estrogen did not attenuate the action of ACTH on adrenal cells on day 170. In fetal adrenal cells obtained on day 170 from MER-25-treated baboons, DHA formation (1.4 +/- 0.6 ng/10(5) cells) was comparably increased (P less than 0.05) to 2.4 +/- 0.2 and 3.0 +/- 0.5 ng/10(5) cells by ACTH in the absence or presence of estradiol. Thus, ACTH remained effective in enhancing DHA by adrenal cells of fetuses exposed in utero to antiestrogen. DHA formation by adrenals of midgestation was increased (P less than 0.05) to 15.4 +/- 4.8 and 27.4 +/- 7.5 ng/10(5) cells, respectively, by LDL and ACTH plus LDL.(ABSTRACT TRUNCATED AT 400 WORDS)