Kubli-Garfias Carlos, Lima-Hernández Francisco J, Vázquez-Ramírez Ricardo, Gómora-Arrati Porfirio, García-Juárez Marcos, González-Flores Oscar
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, México.
Centro de Investigación en Reproducción Animal, Universidad Autónoma de Tlaxcala-CINVESTAV, Plaza Hidalgo S/N, Panotla, Tlaxcala C.P., 90140, México.
J Steroid Biochem Mol Biol. 2016 Oct;163:51-8. doi: 10.1016/j.jsbmb.2016.03.038. Epub 2016 Apr 1.
An investigation of aspects ranging from behavior to molecular electronic structure and physicochemical properties was performed to explore the role of 5α-pregnanedione (5α-DHP), 5β-pregnanedione (5β-DHP) and their precursor progesterone (P) on the concurrent inhibition of the sexual lordosis response in female rats. The concurrent inhibition of lordosis behavior occurs when ovariectomized rodents are primed simultaneously with estradiol (E2) and P. Thus, a second administration of P 40h later fails to induce the expected sexual response that takes place when E2 and P are administered sequentially 40h apart. In this study, it is hypothesized that the modulation of the sexual behavior display depends to some extent on the molecular structure and associated physicochemical properties of steroid hormones such as P and its metabolites. Therefore, these molecules must be studied chemically and structurally to explain their role in sexual behavior, including the concurrent inhibition effect. Analysis of the electronic structure and physicochemical properties demonstrated striking differences in the A-ring region of P, 5α-DHP and 5β-DHP, particularly in atomic charges, dipole moment (DM) and electrostatic potentials. Similarly, the structural differences between the trans (5α-DHP) and cis (5β-DHP) configurations were remarkable. 5α-DHP most significantly promoted the concurrent inhibition of the lordosis behavior, followed by P and 5β-DHP. These data indicate that variations in pregnane structure are related to the extent of the concurrent inhibition effect and also suggest that P may act as a prehormone in certain functions of the central nervous system.
为了探究5α-孕烷二酮（5α-DHP）、5β-孕烷二酮（5β-DHP）及其前体孕酮（P）在雌性大鼠性行为弓背反应同步抑制中的作用，对从行为到分子电子结构和物理化学性质等方面进行了研究。当去卵巢的啮齿动物同时用雌二醇（E2）和P预处理时，会出现性行为弓背反应的同步抑制。因此，在40小时后再次给予P不能诱导出当E2和P间隔40小时顺序给药时所发生的预期性行为反应。在本研究中，假设性行为表现的调节在一定程度上取决于甾体激素如P及其代谢产物的分子结构和相关物理化学性质。因此，必须对这些分子进行化学和结构研究，以解释它们在性行为中的作用，包括同步抑制作用。对电子结构和物理化学性质的分析表明，P、5α-DHP和5β-DHP的A环区域存在显著差异，特别是在原子电荷、偶极矩（DM）和静电势方面。同样，反式（5α-DHP）和顺式（5β-DHP）构型之间的结构差异也很显著。5α-DHP最显著地促进了性行为弓背反应的同步抑制，其次是P和5β-DHP。这些数据表明孕烷结构的变化与同步抑制作用的程度有关，也表明P可能在中枢神经系统的某些功能中作为前体激素起作用。
