Behavioral effects of systemic transforming growth factor-alpha in Syrian hamsters.
The growth factor, transforming growth factor-alpha (TGF-alpha) is strongly expressed in the hypothalamic circadian pacemaker, the suprachiasmatic nucleus (SCN). TGF-alpha is one of several SCN peptides recently suggested to function as a circadian output signal for the regulation of locomotor activity rhythms in nocturnal rodents. When infused in the brain, TGF-alpha suppresses activity. TGF-alpha suppresses other behaviors as well including feeding, resulting in weight loss. Elevated TGF-alpha is correlated with some cancers, and it is possible the TGF-alpha and its receptor, the epidermal growth factor receptor (EGFR), mediate fatigue and weight loss associated with cancer. If true for cancers outside of the brain, then systemic TGF-alpha should also affect behavior. We tested this hypothesis in hamsters with intraperitoneal injections or week-long subcutaneous infusions of TGF-alpha. Both treatments suppressed activity and infusions caused reduced food consumption and weight loss. To identify areas of the brain that might mediate these effects of systemic TGF-alpha, we used immunohistochemistry to localize cells with an activated MAP kinase signaling pathway (phosphorylated ERK1). Cells were activated in two hypothalamic areas, the paraventricular nucleus and a narrow region surrounding the third ventricle. These sites could not only be targets of TGF-alpha produced in the SCN but could also mediate effects of elevated TGF-alpha from tumors both within and outside the central nervous system.
Gilbert
Jenifer
J
Department of Biology, Northeastern University, Boston, MA 02115, United States.
Davis
Fred C
FC
D000818:Animals; D006224:Cricetinae; D004435:Eating / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D055104:Infusions, Subcutaneous; D007274:Injections, Intraperitoneal; D008297:Male; D008647:Mesocricetus; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D020542:Third Ventricle / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D015431:Weight Loss / Q000187:drug effects*
D016211:Transforming Growth Factor alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3