TY - JOUR
T1 - Expression of CRHR1 and CRHR2 in mouse pituitary and adrenal gland
T2 - Implications for HPA system regulation
AU - Müller, M. B.
AU - Preil, J.
AU - Renner, U.
AU - Zimmermann, S.
AU - Kresse, A. E.
AU - Stalla, G. K.
AU - Keck, M. E.
AU - Holsboer, F.
AU - Wurst, W.
PY - 2001
Y1 - 2001
N2 - Deficiency of corticotropin-releasing hormone receptor 1 (CRHR1) reduces anxiety-related behavior in mice and severely impairs the stress response of the hypothalamic-pituitary-adrenocortical (HPA) system. Most recently, we could show that severe emotional stressors induce a significant rise in plasma ACTH even in mice deficient for the CRHR1 (Crhr1-/-) which is, however, not accompanied by an increase in plasma corticosterone concentration, suggesting that CRHR1 might be directly involved in the regulation of adrenal corticosterone release. We therefore used the Crhr1-/- mouse model to clarify the potential role of adrenal CRHR1 in the regulation of the HPA system and, in particular, of corticosterone secretion. In Crhr1-/- mice, intravenous ACTH administration failed to stimulate corticosterone secretion despite a significant upregulation of ACTH receptor mRNA levels in the adrenal cortex of these mutants. Further, by means of RT-PCR and in situ hybridization analyses, we could provide first evidence that both CRHR1 and CRHR2 are expressed in the mouse pituitary and adrenal cortex. Stimulation of pituitary CRHR2 does not induce ACTH secretion either in vitro or in vivo. Our data strongly suggest that CRHR1 plays a crucial role in the release of corticosterone from the adrenal cortex, independently of pituitary function. The existence of an intra-adrenal CRH/CRHR1 regulatory system which contributes to the corticosteroid secretory activity adds to the complexity of HPA system regulation and stress hormone homeostasis.
AB - Deficiency of corticotropin-releasing hormone receptor 1 (CRHR1) reduces anxiety-related behavior in mice and severely impairs the stress response of the hypothalamic-pituitary-adrenocortical (HPA) system. Most recently, we could show that severe emotional stressors induce a significant rise in plasma ACTH even in mice deficient for the CRHR1 (Crhr1-/-) which is, however, not accompanied by an increase in plasma corticosterone concentration, suggesting that CRHR1 might be directly involved in the regulation of adrenal corticosterone release. We therefore used the Crhr1-/- mouse model to clarify the potential role of adrenal CRHR1 in the regulation of the HPA system and, in particular, of corticosterone secretion. In Crhr1-/- mice, intravenous ACTH administration failed to stimulate corticosterone secretion despite a significant upregulation of ACTH receptor mRNA levels in the adrenal cortex of these mutants. Further, by means of RT-PCR and in situ hybridization analyses, we could provide first evidence that both CRHR1 and CRHR2 are expressed in the mouse pituitary and adrenal cortex. Stimulation of pituitary CRHR2 does not induce ACTH secretion either in vitro or in vivo. Our data strongly suggest that CRHR1 plays a crucial role in the release of corticosterone from the adrenal cortex, independently of pituitary function. The existence of an intra-adrenal CRH/CRHR1 regulatory system which contributes to the corticosteroid secretory activity adds to the complexity of HPA system regulation and stress hormone homeostasis.
UR - http://www.scopus.com/inward/record.url?scp=0034862995&partnerID=8YFLogxK
U2 - 10.1210/endo.142.9.8491
DO - 10.1210/endo.142.9.8491
M3 - Article
C2 - 11517194
AN - SCOPUS:0034862995
SN - 0013-7227
VL - 142
SP - 4150
EP - 4153
JO - Endocrinology
JF - Endocrinology
IS - 9
ER -