Regulation of the developing hypothalamic-pituitary-adrenal axis in corticotropin releasing hormone receptor 1-deficient mice.
During postnatal development, mice undergo a so-called stress hyporesponsive period, which is characterized by low basal corticosterone levels and the inability of mild stressors to induce a corticosterone response. The stress hyporesponsiveness is in part regulated by maternal factors. Twenty-four hours of deprivation results in an activation of basal and stress-induced corticosterone and a down-regulation of corticotropin releasing hormone (CRH), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) expression in the brain. It has been hypothesized that the CRH receptor 1 (CRHr1) may play an important regulatory role during development by mediating the effects of maternal deprivation. Using CRHr1-deficient mice we examined the role of this receptor on the maternal deprivation effects and in regulating the expression of hypothalamic-pituitary-adrenal axis-related genes. We could demonstrate that the CRHr1 is essential for the activation of the corticosterone response following maternal deprivation, most likely due to the lack of the receptor in the pituitary. Furthermore, we could show that the CRHr1 is regulating the expression of CRH and MRs. In contrast, effects of maternal deprivation during postnatal development on GRs are not mediated by this receptor.
Schmidt
M V
MV
Leiden-Amsterdam Center for Drug Research, and Leiden University Medical Center, Division of Medical Pharmacology, PO Box 9502, 2300 RA Leiden, The Netherlands. m.schmidt@lacdr.leidenuniv.nl
Schmidt
M
M
Oitzl
M S
MS
Müller
M B
MB
Ohl
F
F
Wurst
W
W
Holsboer
F
F
Levine
S
S
De Kloet
E R
ER
D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000254:growth & development / Q000378:metabolism*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000254:growth & development / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D001127:Arginine Vasopressin; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone