title: Enhanced pelvic responses to stressors in female CRF-overexpressing mice.
abstract: Acute stress affects gut functions through the activation of corticotropin-releasing factor (CRF) receptors. The impact of acute stress on pelvic viscera in the context of chronic stress is not well characterized. We investigated the colonic, urinary, and locomotor responses monitored as fecal pellet output (FPO), urine voiding, and ambulatory activity, respectively, in female and male CRF-overexpressing (CRF-OE) mice, a chronic stress model, and their wild-type littermates (WTL). Female CRF-OE mice, compared with WTL, had enhanced FPO to 2-min handling (150%) and 60-min novel environment (155%) but displayed a similar response to a 60-min partial restraint stress. Female CRF-OE mice, compared with WTL, also had a significantly increased number of urine spots (7.3 +/- 1.4 vs. 1.3 +/- 0.8 spots/h) and lower locomotor activity (246.8 +/- 47.8 vs. 388.2 +/- 31.9 entries/h) to a novel environment. Male CRF-OE mice and WTL both responded to a novel environment but failed to show differences between them in colonic and locomotor responses. Male WTL, compared with female WTL, had higher FPO (113%). In female CRF-OE mice, the CRF(1)/CRF(2) receptor antagonist astressin B and the selective CRF(2) receptor agonist mouse urocortin 2 (injected peripherally) prevented the enhanced defecation without affecting urine or locomotor responses to novel environment. RT-PCR showed that CRF(1) and CRF(2) receptors are expressed in the mouse colonic tissues. The data show that chronic stress, due to continuous central CRF overdrive, renders female CRF-OE mice to have enhanced pelvic and altered behavioral responses to superimposed mild stressors and that CRF(1)-initiated colonic response is counteracted by selective activation of CRF(2) receptor.
authors.affiliation: CURE: Digestive Diseases Research Center and Center for Neurovisceral Sciences and Women's Health, Department of Medicine, Division of Digestive Diseases, University of California, Los Angeles, CA 90073, USA. mmuluget@ucla.edu
authors.forename: M
authors.initials: M
authors.lastname: Million
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: M P
authors.initials: MP
authors.lastname: Stenzel-Poore
authors.forename: S C
authors.initials: SC
authors.lastname: Coste
authors.forename: P Q
authors.initials: PQ
authors.lastname: Yuan
authors.forename: C
authors.initials: C
authors.lastname: Lamy
authors.forename: J
authors.initials: J
authors.lastname: Rivier
authors.forename: T
authors.initials: T
authors.lastname: Buffington
authors.forename: Y
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage* / Q000494:pharmacology; D003672:Defecation / Q000187:drug effects*; D004777:Environment; D005260:Female; D006234:Handling, Psychological; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010388:Pelvis / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors; D014554:Urination / Q000187:drug effects; D054832:Urocortins; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C120841:astressin B; C518358:urocortin 2, mouse; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone