title: Src kinase signaling mediates estrous behavior induced by 5β-reduced progestins, GnRH, prostaglandin E2 and vaginocervical stimulation in estrogen-primed rats.
abstract: The progesterone receptor (PR) is a dual function protein that acts in the nucleus as a transcriptional factor and at the cytoplasm as a scaffold for the Src-MAPK signaling pathway. Several agents lacking affinity for the PR, such as 5β-reduced progestins, GnRH or prostaglandin E(2) (PGE(2)) facilitate estrous behavior in ovariectomized (ovx), estrogen-primed rats yet their action is blocked by the antiprogestin RU486. We hypothesize that these agents act by using the PR-Src-mitogen activated protein kinase alternative pathway. To test this hypothesis we used PP2, a specific inhibitor of the Src kinase family. Intraventricular infusion of 30 μg of PP2, 30 min before behavioral testing, significantly attenuated estrous behaviors induced in estradiol benzoate (E(2)B)-primed rats by 5β-dihydroprogesterone (5β-DHP), 5β-pregnan-3β-ol-20-one (5β,3β-Pgl), GnRH, PGE(2) and by manual flank/vaginocervical stimulation. These results suggest that the Src signaling system, by activating mitogen-activated protein kinases, participates in the facilitation of estrous behavior in E(2)B-primed rats induced by agents lacking affinity for the PR.
authors.affiliation: Centro de Investigación en Reproducción Animal, Universidad Autónoma de Tlaxcala-CINVESTAV, México.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Lima-Hernández
authors.forename: Carlos
authors.initials: C
authors.lastname: Beyer
authors.forename: Porfirio
authors.initials: P
authors.lastname: Gómora-Arrati
authors.forename: Marcos
authors.initials: M
authors.lastname: García-Juárez
authors.forename: José L
authors.initials: JL
authors.lastname: Encarnación-Sánchez
authors.forename: Anne M
authors.initials: AM
authors.lastname: Etgen
authors.forename: Oscar
authors.initials: O
authors.lastname: González-Flores
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D004971:Estrus / Q000187:drug effects*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D010812:Physical Stimulation; D011372:Progestins / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014621:Vagina / Q000187:drug effects / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D011372:Progestins; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D019061:src-Family Kinases; D015232:Dinoprostone