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脱氢表雄酮及其硫酸盐在妊娠狒狒(豚尾狒狒)雌激素生成中的利用

Utilization of dehydroepiandrosterone and its sulphate for oestrogen production by pregnant baboons (Papio papio).

作者信息

Townsley J D

出版信息

Acta Endocrinol (Copenh). 1976 Apr;81(4):830-8. doi: 10.1530/acta.0.0810830.

DOI:10.1530/acta.0.0810830
PMID:176856
Abstract

The effect of varying maternal circulating 3beta-hydroxy-5-androsten-17-one (D) and its sulphate (DS) on urinary oestrogen (Oe) excretion by baboons was determined between 65 and 174 days gestation (term = 184 days). Oe (mainly oestrone) was determined by radioimmunoassay after enzymic hydrolysis of conjugates. Increments in Oe were estimated from the difference between Oe during 5 days pre- and post-treatment. Oestradiol-17beta (5 mg in 5.0 ml saline-ethanol, 1:1) administered iv increased (P less than 0.001) Oe by 2.46 +/- 0.71, 7 (mean, mg +/- SD, number of experiments). The response to 100 mg D (3.20 +/- 1.50, 7) was greater (P less than 0.001) than that due to 100 mg DS (0.03 +/- 0.75, 7). The response to DS was not different from that due to saline-ethanol alone (-0.05 +/- 0.27, 5). Betamethasone (9alpha-fluoro-11beta,17,21-trihydroxy-16beta-methyl-1,4-pregnadiene-3,20-dione) administration (3 mg bi-daily, im) caused an approximately 90% reduction in Oe within 4 days. In animals treated chronically with betamethasone the response due to 100 mg D (2.74 +/- 1.04, 5) was again greater (P less than 0.001) that that due to 100 mg DS (0.10 +/- 0.09, 5). ACTH (8 U or 40 U, im, N = 11) produced a variable but not significant mean change in Oe at either dose level. Metyrapone (300 mg every 4 h for 6 doses) increased (P less than 0.005) Oe (0.77 +/- 0.48, 5). It is concluded that in normal pregnant animals and those treated with betamethasone, in which endogenous levels of D and DS are presumably reduced, D is preferentially used over DS for oestrogen produced. Variations in DS availability do not produce marked changes in oestrogen production. This suggest that rapid increases in oestrogen production, as occur for example close to term, may result from increased availability of D rather than DS. The variable responses to ACTH and the increase in Oe following metyrapone administration are compatible with significant foetal contributions of oestrogen precursors, the production of which is under ACTH control.

摘要

在妊娠65至174天(足月为184天)期间,测定了不同水平的母体循环3β - 羟基 - 5 - 雄烯 - 17 - 酮(D)及其硫酸盐(DS)对狒狒尿雌激素(Oe)排泄的影响。通过对结合物进行酶水解后,采用放射免疫分析法测定Oe(主要为雌酮)。根据治疗前5天和治疗后5天Oe的差值估算Oe的增量。静脉注射雌二醇 - 17β(5mg溶于5.0ml生理盐水 - 乙醇,1:1)使Oe增加(P<0.001),增加量为2.46±0.71(均值,mg±标准差,实验次数7次)。100mg D引起的反应(3.20±1.50,7次实验)比100mg DS引起的反应(0.03±0.75,7次实验)更大(P<0.001)。DS引起的反应与单独使用生理盐水 - 乙醇引起的反应(-0.05±0.27,5次实验)无差异。每日两次肌肉注射倍他米松(9α - 氟 - 11β,17,21 - 三羟基 - 16β - 甲基 - 1,4 - 孕二烯 - 3,20 - 二酮)(3mg),4天内Oe降低约90%。在长期接受倍他米松治疗的动物中,100mg D引起的反应(2.74±1.04,5次实验)再次比100mg DS引起的反应(0.10±0.09,5次实验)更大(P<0.001)。促肾上腺皮质激素(8U或40U,肌肉注射,N = 11)在任一剂量水平下均使Oe产生可变但不显著的平均变化。甲吡酮(每4小时300mg,共6剂)使Oe增加(P<0.005),增加量为0.77±0.48(5次实验)。结论是,在正常妊娠动物和接受倍他米松治疗的动物中,内源性D和DS水平可能降低,雌激素生成优先利用D而非DS。DS可用性的变化不会使雌激素生成产生显著变化。这表明,例如在接近足月时发生的雌激素生成快速增加可能是由于D而非DS可用性增加所致。对促肾上腺皮质激素的可变反应以及甲吡酮给药后Oe的增加与雌激素前体的显著胎儿贡献相一致,其产生受促肾上腺皮质激素控制。

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