Matsunaga Masahiro, Okuhara Keisuke, Ukena Kazuyoshi, Tsutsui Kazuyoshi
Laboratory of Brain Sciences, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan.
Brain Res. 2004 May 8;1007(1-2):160-6. doi: 10.1016/j.brainres.2004.02.017.
We have demonstrated recently that the quail brain possesses the cholesterol side-chain cleavage enzyme (cytochrome P450scc) and 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3beta-HSD) and produces pregnenolone, pregnenolone sulfate and progesterone from cholesterol. The present study was therefore conducted to investigate progesterone metabolism in the brain of adult male quails. Employing biochemical techniques combined with HPLC and TLC analyses, the conversion of progesterone to 3beta,5beta-tetrahydroprogesterone (3beta,5beta-THP) via 5beta-dihydroprogesterone (5beta-DHP) was found in the brain. There was a clear regional difference in progesterone metabolism. The formation of 3beta,5beta-THP was high in the diencephalon and cerebrum and low in the cerebellum. Based on such a region-dependent formation of 3beta,5beta-THP, the action of this progesterone metabolite on preoptic neurons in the diencephalon was then investigated electrophysiologically using a brain slice preparation of the adult male. 3beta,5beta-THP significantly increased, in a dose-related way, the spontaneous firing activity of subsets of preoptic neurons. The stimulatory effect of 3beta,5beta-THP was greater than that of progesterone and its threshold concentration ranged between 10(-6) and 3x10(-6) M. In 33% of cells in the preoptic area, however, 3beta,5beta-THP did not change the spontaneous firing activity even at the high concentration, 10(-5) M. Because preoptic neurons are considered to be involved in the regulation of a variety of male reproductive behaviors, 3beta,5beta-THP may regulate some reproductive behavior through the mechanism that provokes such a stimulation.
我们最近已证明鹌鹑脑具有胆固醇侧链裂解酶（细胞色素P450scc）和3β-羟基类固醇脱氢酶/Δ5-Δ4-异构酶（3β-HSD），并能从胆固醇生成孕烯醇酮、硫酸孕烯醇酮和孕酮。因此，本研究旨在调查成年雄性鹌鹑脑中孕酮的代谢情况。采用结合高效液相色谱（HPLC）和薄层层析（TLC）分析的生化技术，发现在脑中孕酮可经5β-二氢孕酮（5β-DHP）转化为3β,5β-四氢孕酮（3β,5β-THP）。孕酮代谢存在明显的区域差异。3β,5β-THP的生成在间脑和大脑中较高，而在小脑中较低。基于3β,5β-THP这种区域依赖性的生成情况，随后使用成年雄性鹌鹑的脑片标本，通过电生理学方法研究了这种孕酮代谢产物对间脑视前神经元的作用。3β,5β-THP以剂量相关的方式显著增加了视前神经元亚群的自发放电活动。3β,5β-THP的刺激作用大于孕酮，其阈值浓度在10-6至3×10-6 M之间。然而，在视前区33%的细胞中，即使在高浓度10-5 M时，3β,5β-THP也不会改变自发放电活动。由于视前神经元被认为参与多种雄性生殖行为的调节，3β,5β-THP可能通过引发这种刺激的机制来调节某些生殖行为。
