Zhou Yingqiao, Kang Jian, Chen Di, Han Ningning, Ma Haitian
Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
PLoS One. 2015 May 11;10(5):e0124511. doi: 10.1371/journal.pone.0124511. eCollection 2015.
Dehydroepiandrosterone (DHEA) is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD) and testosterone (T) were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectively. Estradiol (E2) content significantly increased at 6h after DHEA administration, which was 113% higher than that in control group. Gavage with DHEA could significantly reduce 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA level at 3-12h and 17β-hydroxysteroid dehydrogenase (17β-HSD) mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24, and 48 h. It is interesting that administration of DHEA caused a significant increase of 17β-HSD, 3β-HSD and aromatase mRNA levels in adrenal. The AD and T contents also markedly increased by 537% and 2737% after DHEA administration in ovariectomised rats, in company with a significant increase in 17β-HSD and 3β-HSD mRNA levels and decreased aromatase mRNA level in adrenal. However, DHEA administration did not restore the decreased E2, estrone (E1), and progesterone (P) caused by the removal of the ovaries in females. These results clearly illustrated that exogenous DHEA is preferentially converted into androgens in adrenal, while its conversion to estrogens mainly happens in the ovary through steroidogenic enzyme in female rats.
脱氢表雄酮(DHEA)对人体健康很重要,尤其是对女性。所有雌激素以及几乎一半的雄激素都是由外周组织中的DHEA合成的。然而,女性体内DHEA生物转化的机制和确切靶组织尚不完全清楚。本研究表明,在给雌性大鼠注射DHEA后3小时观察到雄烯二酮(AD)和睾酮(T)的含量最高,分别比对照组高264%和8000%。给药后6小时雌二醇(E2)含量显著增加,比对照组高113%。灌胃DHEA可显著降低卵巢中3 - 12小时的3β - 羟基类固醇脱氢酶(3β - HSD)mRNA水平以及12小时的17β - 羟基类固醇脱氢酶(17β - HSD)mRNA水平,同时在6、24和48小时增加芳香化酶mRNA水平。有趣的是,给予DHEA会导致肾上腺中17β - HSD、3β - HSD和芳香化酶mRNA水平显著增加。在去卵巢大鼠中给予DHEA后,AD和T含量也显著增加了537%和2737%,同时肾上腺中17β - HSD和3β - HSD mRNA水平显著增加,芳香化酶mRNA水平降低。然而,给予DHEA并未恢复雌性大鼠因卵巢切除而降低的E2、雌酮(E1)和孕酮(P)水平。这些结果清楚地表明,外源性DHEA在雌性大鼠体内优先在肾上腺中转化为雄激素,而其向雌激素的转化主要发生在卵巢中通过类固醇生成酶进行。