Sex-biased cellular signaling: molecular basis for sex differences in neuropsychiatric diseases.
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.
Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and University of Pennsylvania, USA.
Rita J
RJ
Valentino
Department of Psychology and Neuroscience Program, Temple University, USA.
Debra A
DA
Bangasser
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000502:physiology; D008297:Male; D001523:Mental Disorders / Q000503:physiopathology*; D051379:Mice; D012727:Sex Characteristics; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D003346:Corticotropin-Releasing Hormone
Gs-GTP binding protein; amygdala; arousal; corticotropin-releasing factor; locus coeruleus; norepinephrine; stress; β-arrestin