Havlíková Helena, Hill Martin, Kancheva Lyudmila, Vrbíková Jana, Pouzar Vladimír, Cerny Ivan, Kancheva Radmila, Stárka Luboslav
Institute of Endocrinology, Národní trida 8, CZ 116 94 Prague 1, Czech Republic.
J Clin Endocrinol Metab. 2006 Aug;91(8):3092-9. doi: 10.1210/jc.2005-2785. Epub 2006 May 23.
Pregnanolone isomers (PI) with a hydroxy group in the 3alpha-position are neuroinhibitors operating via positive modulation of GABA(A) receptors. The 3beta-PI and sulfates of PI and pregnenolone exert the opposite effect. In addition to the brain's in situ synthesis, some circulating steroids can penetrate the blood-brain barrier.
To assess the physiological impact of peripheral endogenous neuroactive pregnanolone isomers and their polar conjugates in women, serum allopregnanolone (P3alpha5alpha), isopregnanolone (P3beta5alpha), pregnanolone (P3alpha5beta), epipregnanolone (P3beta5beta), pregnenolone, estradiol (including their polar conjugates), and additional steroids were measured in 16 women in the follicular and luteal phases of the menstrual cycle using gas chromatography/mass spectrometry and RIA for the analysis. Linear models and Spearman's correlations were used for data evaluation.
The levels of conjugated PI were from one to almost three orders of magnitude higher in comparison with the free steroids. The results indicate that a substantial proportion of the progesterone is metabolized in the sequence progesterone-->5beta-dihydroprogesterone-->P3alpha5beta-->conjugated P3alpha5beta. The sulfation of PI and particularly of P3alpha5beta moderates the levels of free PI and restrains estradiol biosynthesis via progesterone degradation. PI including the conjugates reflected changing progesterone formation during the menstrual cycle. In the follicular phase, the positive correlation with conjugated pregnenolone, the independence of progesterone, and the negative age relationships of PI indicate their adrenal origin. The dependence on progesterone and the independence of conjugated pregnenolone suggest a gonadal source of PI in the luteal phase. The neuroactivating PI prevailed over neuroinhibiting PI.
在3α位带有羟基的孕烷醇酮异构体（PI）是通过对GABA(A)受体的正向调节起作用的神经抑制剂。3β-PI以及PI和孕烯醇酮的硫酸盐则发挥相反的作用。除了大脑的原位合成外，一些循环类固醇可以穿透血脑屏障。
为了评估外周内源性神经活性孕烷醇酮异构体及其极性共轭物对女性的生理影响，在月经周期的卵泡期和黄体期对16名女性的血清别孕烷醇酮（P3α5α）、异孕烷醇酮（P3β5α）、孕烷醇酮（P3α5β）、表孕烷醇酮（P3β5β）、孕烯醇酮、雌二醇（包括它们的极性共轭物）以及其他类固醇进行了测量，采用气相色谱/质谱法和放射免疫分析法进行分析。使用线性模型和斯皮尔曼相关性进行数据评估。
与游离类固醇相比，共轭PI的水平高出一到近三个数量级。结果表明，相当一部分孕酮按孕酮→5β-二氢孕酮→P3α5β→共轭P3α5β的顺序代谢。PI尤其是P3α5β的硫酸化会调节游离PI的水平，并通过孕酮降解抑制雌二醇的生物合成。包括共轭物在内的PI反映了月经周期中孕酮生成的变化。在卵泡期，与共轭孕烯醇酮的正相关、与孕酮的独立性以及PI与年龄的负相关表明它们起源于肾上腺。对孕酮的依赖性和与共轭孕烯醇酮的独立性表明黄体期PI的来源是性腺。神经激活型PI占主导地位，超过神经抑制型PI。
