Albrecht E D, Henson M C, Walker M L, Pepe G J
Department of Obstetrics/Gynecology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Endocrinology. 1990 Jun;126(6):3083-8. doi: 10.1210/endo-126-6-3083.
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)
我们曾报道，雌激素可抑制狒狒胎儿肾上腺在妊娠中期由促肾上腺皮质激素（ACTH）刺激生成脱氢表雄酮（DHA）的过程。由于胎儿肾上腺的调节会随着妊娠进展而变化，雌激素对胎儿肾上腺类固醇生成的作用可能也取决于胎儿肾上腺的成熟程度。在本研究中，我们通过测定ACTH和雌激素对取自妊娠中期和晚期狒狒胎儿以及在整个妊娠晚期给予抗雌激素MER - 25的动物胎儿的肾上腺细胞生成DHA的影响，来检验这种可能性。因为低密度脂蛋白（LDL）为胎儿肾上腺提供底物，所以我们还确定雌激素的作用是否通过LDL摄取介导。从未处理动物的妊娠第100天（妊娠中期；n = 7）和第170天（妊娠晚期；n = 6；足月为第184天）的狒狒胎儿以及在第140 - 170天用MER - 25（25 mg/kg体重·天；n = 7）处理的母亲所生的第170天胎儿身上取出肾上腺。用0.2%胶原酶分散细胞，并在含有10 nM ACTH、10⁻⁶ M雌二醇和/或500微克LDL的4 ml培养基199中于37℃孵育3小时。通过放射免疫分析（RIA）测定培养基中DHA的分泌量。在妊娠中期，平均（±标准误）基础DHA生成量（每10⁵个细胞/3小时的纳克数）为5.8±2.1，ACTH可使其增加（P＜0.01）至20.0±5.9。虽然单独的雌二醇没有作用，但雌二醇可阻止ACTH使DHA增加。妊娠晚期肾上腺的基础DHA生成量（0.7±0.3纳克/10⁵个细胞）低于（P＜0.01）妊娠中期。在接近足月时，无论有无雌二醇，ACTH均以类似方式增加（P＜0.01）DHA（有雌二醇时为2.0±0.4，无雌二醇时为1.7±0.4）。因此，与第100天不同，在第170天雌激素不会减弱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，无论有无雌二醇，ACTH均可使DHA生成量（1.4±0.6纳克/10⁵个细胞）类似地增加（P＜0.05）至2.4±0.2和3.0±0.5纳克/10⁵个细胞。因此，ACTH对子宫内暴露于抗雌激素的胎儿的肾上腺细胞增强DHA生成仍有效。妊娠中期肾上腺分别通过LDL以及ACTH加LDL使DHA生成量增加（P＜0.05）至15.4±4.8和27.4±7.5纳克/10⁵个细胞。（摘要截短至400字）
