Activation of the baboon fetal pituitary-adrenocortical axis at midgestation by estrogen: responsivity of the fetal adrenal gland to adrenocorticotropic hormone in vitro.
Activation of the baboon fetal pituitary-adrenocortical axis at midgestation by estrogen: responsivity of the fetal adrenal gland to adrenocorticotropic hormone in vitro.
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雌激素对妊娠中期狒狒胎儿垂体-肾上腺皮质轴的激活：胎儿肾上腺对体外促肾上腺皮质激素的反应。
DOI：
10.1095/biolreprod53.5.996
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发表时间：
1995
影响因子：
3.6
通讯作者：
Pepe,GJ
中科院分区：
文献类型：
--
作者：
Berghorn,KA;Albrecht,ED;Pepe,GJ
我们先前已经证明，胎盘中雌激素诱导的母体皮质醇氧化为皮质醇的变化，调节了胎儿脑下垂体前阿片黑素皮质醇mRNA的表达增加和足月胎儿肾上腺皮质醇形成酶的诱导。为了验证雌激素诱导胎盘皮质醇氧化诱导胎儿垂体促肾上腺皮质激素(ACTH)产生导致胎儿肾上腺对ACTH的反应性增加的假设，在本研究中，我们在体外比较了未处理对照组和妊娠期给予雌激素治疗的动物体外中期胎儿肾上腺对ACTH的敏感性。在第100天(n=7)、第165天(n=5)和第100天(第70-100天；n=10)或雄激素前体治疗(n=3)后，从未经处理的狒狒身上获得胎儿肾上腺。肾上腺切片(15~25 mg)用不含酚红的199培养液灌流(温度37℃，L 100ug/min)，每隔10min收集培养液，测定皮质醇和脱氢表雄酮含量。皮质醇和脱氢表雄酮的分泌在140分钟后达到平衡；因此，基础释放以190-240分钟内的平均类固醇浓度计算。然后用生理盐水或促肾上腺皮质激素在240nmo1、370nmo1和490nmo1的条件下灌流20min，计算240~600min的皮质醇/脱氢表雄酮分泌速率(pg/min/mg)。对照组(9±3)和雌激素组(13±3)大鼠肾上腺基础皮质醇生成量在165天(85±11)天高于100天(P<0.05)。而对照组(30±6)和雌激素组(20±3)，165日龄对照组肾上腺脱氢表雄酮(13±4)显著低于100日龄(20±3)。因此，孕中期(4.93±2.15)显著高于足月(0.16±0.05)，肾上腺脱氢表雄酮/皮质醇分泌比值(1.87±0.38)显著降低(p<；0.05)。各组大鼠输注生理盐水后，皮质醇和脱氢表雄酮的基础分泌量均无明显变化。与之相反，促肾上腺皮质激素使165日龄≥的肾上腺皮质醇分泌量增加了50%(116±20)，而在雌激素处理组(18±3)和未处理的(10±4)日龄则增加了(10±4)。ACTH增加(p<；0.05)雌激素处理的肾上腺在第100天的雄激素产生(p<；0.05)幅度(515%±161%)比对照组(154%±81%)更大(p<；0.05)。这些数据表明，孕中期体内雌激素治疗诱导了胎儿肾上腺脱氢表雄酮和皮质醇的体外分泌比率，这一比率与近期胎儿肾上腺脱氢表雄酮和皮质醇分泌的比率相似，并与ACTH引起的类固醇激素分泌增加有关。因此，我们认为胎儿下丘脑-垂体-肾上腺轴在足月和妊娠中期的激活与胎儿肾上腺对ACTH的反应性增加有关。
We have previously demonstrated that increased expression of fetal pituitary proopiomelanocortin mRNA and the induction of enzymes catalyzing fetal adrenal cortisol formation at term are regulated by estrogen-induced changes in placental oxidation of maternal cortisol to cortisone. To test the hypothesis that induction of fetal pituitary adrenocorticotropic hormone (ACTH) production by estrogen-induced changes in placental cortisol oxidation results in increased responsivity of the fetal adrenal gland to ACTH, in the present study we compared fetal adrenal sensitivity to ACTH in vitro at midgestation in untreated controls and in animals treated at this time in gestation with estrogen. Fetal adrenals were obtained on Day 100 (n = 7) and Day 165 (n = 5; term = Day 184) from untreated baboons and on Day 100 following maternal treatment with estradiol (s.c.; Days 70–100; n = 10) or androgen precursor (n = 3). Adrenal slices (15–25 mg) were perifused (100 µl/min; 37°C) with Medium 199 (no phenol red); media were collected at 10-min intervals and assayed for cortisol and dehydroepiandrosterone. Secretion of cortisol and dehydroepiandrosterone reached equilibrium after 140 min of perifusion; therefore, basal release was calculated as the mean steroid concentrations during 190–240 min. Adrenal slices were then perifused for 20 min with saline or ACTH at 240 (0.001 nmol), 370 (0.01 nmol), and 490 (0.1 nmol) min, and an overall average cortisol/dehydroepiandrosterone secretion rate (pg/min/mg) between 240–600 min was calculated. Basal cortisol production at Day 165 (85 ± 11) exceeded (p< 0.05) that at Day 100 in adrenals of control (9 ± 3) and estrogen-treated (13 ± 3) animals. In contrast, dehydroepiandrosterone production by control adrenals of Day 165 (13 ± 4) was lower than that at Day 100 in control (30 ± 6) and estrogen-treated (20 ± 3) animals. Thus, the ratio of dehydroepiandrosterone:cortisol secretion was significantly (p< 0.05) higher at midgestation (4.93 ± 2.15) than at term (0.16 ± 0.05) and was reduced (p< 0.05) in adrenals of estrogen-treated baboons (1.87 ± 0.38). In all groups, basal secretion of cortisol and dehydroepiandrosterone was not altered after infusion of saline. In contrast, ACTH increased (p< 0.05) cortisol secretion by ≥ 50% in adrenals of Day 165 (116 ± 20) and in those of estrogen-treated (18 ± 3) but not untreated (10 ± 4) baboons of Day 100. ACTH increased (p< 0.05) androgen production by estrogen-treated adrenals of Day 100 to a greater (p< 0.05) extent (515% ± 161%) than that of controls at Day 100 (154% ± 81%). These data indicate that estrogen treatment in vivo at midgestation induced a ratio of dehydroepiandrosterone:cortisol secretion in vitro in fetal adrenals that mimicked the ratio near term and was associated with increased steroid hormone production in response to ACTH. Therefore, we suggest that activation of the fetal hypothalamic-pituitary-adrenal axis at term and at midgestation following maternal estrogen administration is associated with increased responsivity of the fetal adrenal to ACTH.
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影响因子：
4.8
作者：
E. Albrecht;Michael C. Henson;Margaret L. Walker;G. Pepe
通讯作者：
E. Albrecht;Michael C. Henson;Margaret L. Walker;G. Pepe
ACTH 诱导羊胎肾上腺中 ACTH 敏感的腺苷酸环化酶系统的成熟。
DOI：
10.1016/0022-4731(81)90312-5
发表时间：
1981
期刊：
Journal of steroid biochemistry
影响因子：
--
作者：
P. Durand;A. Locatelli;A. Cathiard;A. Dazord;J. Saez
通讯作者：
J. Saez
雌激素对狒狒胎盘中 1lβ-羟基类固醇脱氢酶活性的调节*
DOI：
--
发表时间：
1990
期刊：
影响因子：
--
作者：
S. Baggia;E. Albrecht;G. Pepe
通讯作者：
G. Pepe
影响因子：
4.8
作者：
Carr,BR;Simpson,ER
通讯作者：
Simpson,ER
灵长类胎儿垂体和靶组织功能和生长的肽调节。
DOI：
10.1016/b978-0-12-571144-9.50017-x
发表时间：
1988
期刊：
Recent progress in hormone research
影响因子：
--
作者：
R. Jaffe;J. Mulchahey;A. Di Blasio;M. Martín;Z. Blumenfeld;D. Dumesic
通讯作者：
D. Dumesic