EFFECTS OF ADRENOCORTICOTROPIN ON ADRENAL AND PLASMA - 11-BETA-HYDROXYANDROSTENEDIONE IN THE GUINEA-PIG AND DETERMINATION OF ITS RELATIVE ANDROGEN POTENCY
EFFECTS OF ADRENOCORTICOTROPIN ON ADRENAL AND PLASMA - 11-BETA-HYDROXYANDROSTENEDIONE IN THE GUINEA-PIG AND DETERMINATION OF ITS RELATIVE ANDROGEN POTENCY
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DOI：
10.1016/0039-128x(93)90014-e
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发表时间：
1993-01-01
期刊：
影响因子：
2.7
通讯作者：
BELANGER, A
中科院分区：
文献类型：
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作者：
BELANGER, B;FIET, J;BELANGER, A
为了更好地了解豚鼠肾上腺激素的产生，我们给阉割的成年豚鼠注射促肾上腺皮质激素（ACTH），并在6小时内测定其肾上腺和血浆中C-21和C-19类固醇的水平。注射ACTH后，肾上腺皮质醇和皮质酮的浓度分别增加了近40倍和3倍，而C-21类固醇前体，即孕烯醇酮、17-羟基孕烯醇酮、孕酮和17-羟基孕酮的含量则增加了2至10倍。C-19类固醇水平，即脱氢表雄酮（DHEA），雄烯二酮（4-DIONE），睾酮和11β -羟基雄烯二酮（11β - dione），在肾上腺中也观察到1.5至8倍的增加。在阉割的豚鼠中，基础血浆DHEA、4-DIONE和睾酮水平无法通过放射免疫测定检测到，而11 - β - dione浓度的范围与未阉割的豚鼠相似。在血浆中，ACTH对皮质酮、皮质醇和11β - dione有显著影响。目前的结果表明，尽管豚鼠肾上腺合成了几种C-19类固醇，但即使在给药ACTH后，只有11β - dione由肾上腺分泌进入循环。然后用硅胶植入阉割豚鼠体内评估这种羟基化C-19类固醇的生物活性，结果表明血浆11 - β - dione浓度增加了三倍，但对前列腺重量没有影响。此外，通过使用对雄激素极其敏感的乳腺癌细胞系ZR-75-1细胞，我们发现11β - dione的雄激素效能比双氢睾酮低35倍。
In order to gain a better understanding of adrenal steroid production in guinea pigs, adrenocorticotropin (ACTH) was administered to castrated adult guinea pigs and a series of C-21 and C-19 steroid levels were determined in both adrenals and plasma over a 6-h period. After injection of ACTH, adrenal cortisol and corticosterone concentrations were stimulated by almost 40- and threefold, respectively, whereas the content of C-21 steroid precursors, namely pregnenolone, 17-hydroxypregnenolone, progesterone, and 17-hydroxyprogesterone, was stimulated by two- to 10-fold. Increases of C-19 steroid levels, namely dehydroepiandrosterone (DHEA), androstenedione (4-DIONE), testosterone, and 11beta-hydroxyandrostenedione (11beta-DIONE) ranging from 1.5 to eight times were also observed in the adrenals. In castrated guinea pigs, basal plasma DHEA, 4-DIONE, and testosterone levels were undetectable by radioimmunoassay, whereas 11beta-DIONE concentrations were in a range similar to those in intact animals. In plasma, ACTH had a marked effect on corticosterone, cortisol, and 11beta-DIONE. The present results indicate that although guinea pig adrenals synthesized several C-19 steroids, only 11beta-DIONE was secreted by the adrenals into circulation even after administration of ACTH. The biological activity of this hydroxylated C-19 steroid was then assessed by using silastic implants in castrated guinea pigs, and it was shown that plasma 11beta-DIONE concentrations increased by threefold and had no effect on prostate weight. Moreover, by using ZR-75-1 cells, a mammary cancer cell line extremely sensitive to androgens, we demonstrated that 11beta-DIONE had an androgenic potency 35-fold less than that of dihydrotestosterone.