Effects of corticotropin-releasing hormone (CRH) on the synthesis and secretion of proopiomelanocortin-related peptides in the anterior pituitary: a study using CRH-deficient mice.
Corticotropin-releasing hormone (CRH) mainly regulates the synthesis and secretion of adrenocorticotropin (ACTH) in the anterior pituitary (AP). By using CRH-deficient mice (CRH KO), we investigated the role of CRH in the processing of proopiomelanocortin (POMC), a precursor of ACTH, beta-lipotropic hormone, and beta-endorphin (EP). In the basal condition, the plasma ACTH level was similar in CRH KO and wild-type mice (WT), while its response to pain stress in CRH KO was smaller than that in WT. Immunoreactive (ir) beta-EP contents in the AP of CRH KO were not significantly different from those of WT. In order to determine the different molecule profile of POMC-related peptides between WT and CRH KO, ir beta-EP contents extracted from AP of WT and CRH KO were assayed by gel filtration chromatography. The gel filtration analyses revealed that a higher molecular weight form of ir beta-EP, putative POMC, was increased in CRH KO, but the beta-EP peak level was small and similar between two groups. These results suggest that CRH has little influence on the basal release of ACTH and prohormone convertase-2 processing enzyme. On the other hand, it is essential for ACTH secretion under stress conditions, and CRH would affect on the prohormone convertase-1/3 processing enzyme in AP.
The Third Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Yoshiko
Y
Fukuda
Kazunori
K
Kageyama
Takeshi
T
Nigawara
Yoko
Y
Kasagi
Toshihiro
T
Suda
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D002850:Chromatography, Gel / Q000379:methods; D003346:Corticotropin-Releasing Hormone / Q000172:deficiency* / Q000494:pharmacology / Q000502:physiology; D007016:Hypophysectomy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000097:blood; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000378:metabolism*; D011863:Radioimmunoassay / Q000379:methods; D001615:beta-Endorphin / Q000378:metabolism; D008083:beta-Lipotropin / Q000378:metabolism
D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D008083:beta-Lipotropin