Sex-biased cellular signaling: molecular basis for sex differences in neuropsychiatric diseases.

Abstract:

:The recognition that there are fundamental biological sex differences that extend beyond those that define sexual behavior and reproductive function has inspired the drive toward inclusion of both sexes in research design. This is supported by an underlying clinical rationale that studying both sexes is necessary to elucidate pathophysiology and develop treatments for the entire population. However, at a more basic level, sex differences, like genetic differences, can be exploited to better understand biology. Here, we discuss how sex differences at the molecular level of cell signaling and protein trafficking are amplified to create a state of vulnerability that under the right conditions can result in symptoms of neuropsychiatry disease. Although this dialogue focuses on the specific example of corticotropin-releasing factor, the potential for analogous sex differences in signaling and/or trafficking of receptors for other neuromodulators has broad biological and therapeutic implications. :El reconocer que hay diferencias biológicas sexuales fundamentales que se extienden más allá de lo que define la conducta sexual y la función reproductiva ha inspirado el camino hacia la inclusión de ambos sexos en los diseños de investigación. Esto se sustenta en una justificación clínica fundamental acerca de la necesidad del estudio de ambos sexos para aclarar la fisiopatología y desarrollar tratamientos para toda la población. Sin embargo, a un nivel más básico, para una mejor comprensión de la biología se puede sacar provecho tanto de las diferencias por sexo como de las diferencias genéticas. En este artículo se discute cómo las diferencias sexuales a nivel molecular de las señales celulares y del tránsito de proteínas son amplificadas para crear un estado de vulnerabilidad que bajo condiciones adecuadas pueden provocar síntomas de una enfermedad neuropsiquiátrica. Aunque este diálogo se concentra en el ejemplo específico del factor liberador de corticotropina, el potencial de las diferencias sexuales análogas en las señales y/o tránsito de los receptores para otros neuromoduladores tiene amplias implicancias biológicas y terapéuticas. :L'existence de différences biologiques fondamentales selon le sexe, au-delà de celles qui définissent le comportement sexuel et la fonction reproductrice, est à l'origine de l'inclusion des deux sexes dans les schémas de recherche. Cette conception est soutenue par une justification clinique sous-jacente stipulant que l'étude des deux sexes est nécessaire pour comprendre la physiopathologie et développer des traitements pour toute la population. Toutefois, à un niveau plus basique, les différences selon le sexe, comme les différences génétiques, peuvent être exploitées pour mieux comprendre la biologie. Nous analysons ici comment les différences selon le sexe, au niveau moléculaire de la signalisation cellulaire et de la circulation des protéines, sont amplifiées pour créer un état de vulnérabilité qui peut résulter, dans certaines conditions, en symptômes de maladie neuropsychiatrique. Cette discussion porte sur l'exemple spécifique du facteur de libération de la corticotrophine, mais l'existence de différences analogues selon le sexe dans la signalisation et/ou la circulation des récepteurs d'autres neuromodulateurs, a d'importantes implications biologiques et thérapeutiques.

authors

Valentino RJ,Bangasser DA

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

385-393

issue

4

eissn

1294-8322

issn

1958-5969

journal_volume

18

pub_type

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