title: The importance of the chemical structure of pregnanes in the concurrent inhibition of estrous behavior in the female rat.
abstract: 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.
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, México. Electronic address: kubli@unam.mx.
authors.forename: Carlos
authors.initials: C
authors.lastname: Kubli-Garfias
authors.affiliation: Centro de Investigación en Reproducción Animal, Universidad Autónoma de Tlaxcala-CINVESTAV, Plaza Hidalgo S/N, Panotla, Tlaxcala C.P., 90140, México.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Lima-Hernández
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, México.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vázquez-Ramírez
authors.affiliation: Centro de Investigación en Reproducción Animal, Universidad Autónoma de Tlaxcala-CINVESTAV, Plaza Hidalgo S/N, Panotla, Tlaxcala C.P., 90140, México.
authors.forename: Porfirio
authors.initials: P
authors.lastname: Gómora-Arrati
authors.affiliation: Centro de Investigación en Reproducción Animal, Universidad Autónoma de Tlaxcala-CINVESTAV, Plaza Hidalgo S/N, Panotla, Tlaxcala C.P., 90140, México.
authors.forename: Marcos
authors.initials: M
authors.lastname: García-Juárez
authors.affiliation: Centro de Investigación en Reproducción Animal, Universidad Autónoma de Tlaxcala-CINVESTAV, Plaza Hidalgo S/N, Panotla, Tlaxcala C.P., 90140, México.
authors.forename: Oscar
authors.initials: O
authors.lastname: González-Flores
mesh_terms: D043582:5-alpha-Dihydroprogesterone / Q000494:pharmacology*; D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008297:Male; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism; D013238:Stereotaxic Techniques; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D011374:Progesterone; D004958:Estradiol; D043582:5-alpha-Dihydroprogesterone
keywords: 5α-DHP; 5β-DHP; Ab initio molecular properties; Concurrent inhibition; Lordosis; Progesterone metabolites