Modulation of corticotropin-releasing hormone receptor type 2 mRNA expression by CRH deficiency or stress in the mouse heart.
The actions of corticotropin-releasing hormone (CRH) and the related peptides are coordinated by two receptors, CRH receptor type 1 (CRH-R1) and CRH receptor type 2 (CRH-R2). In this study, we examined the effects of CRH deficiency and/or stress due to physically restraint or lipopolysaccharide (LPS) administration on expression of transcripts for CRH-R2 (CRH-R2 mRNA) as well as urocortin (UCN) mRNA in the atria and ventricle using female and male CRH-deficient (knockout, KO) mice. We show that restraint stress caused a significant increase in plasma corticosterone levels in female CRH KO mice, but LPS administration induced a significant increase in plasma corticosterone levels in both female and male CRH KO mice. CRH deficiency caused a robust decrease in basal levels of CRH-R2 mRNA and a significant increase of UCN mRNA expression in the atria and ventricle of female as well as male mice. Restraint stress markedly reduced CRH-R2 mRNA and increased UCN mRNA expression on atria as well as ventricle in both female and male wild-type (WT) mice. Following LPS injection to both female and male mice, CRH-R2 mRNA expression was decreased and UCN mRNA expression was increased in the atria and ventricle of both WT and CRH KO mice in each sex. We speculate that stress or lack of CRH may increase urocortin, which in turn down-regulates CRH-R2 mRNA expression in the heart. These data indicate: (1) that lack of CRH may decreases cardiac CRH-R2 mRNA expression in basal state, (2) that inhibitory effect of CRH deficiency on cardiac CRH-R2 mRNA expression in stress condition seems to be more closely linked to type of stressor than rise in plasma corticosterone level.
Pournajafi Nazarloo
Hossein
H
Second Department of Internal Medicine, Kochi Medical School, Kohasu, Okoh-cho, Nankoku 783-8505, Japan. nazarloo@yahoo.com
Tanaka
Yasushi
Y
Dorobantu
Maria
M
Hashimoto
Kozo
K
D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological; D054832:Urocortins
C101531:CRF receptor type 2; D017931:DNA Primers; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone