Differential disinhibition of the neonatal hypothalamic- pituitary-adrenal axis in brain-specific CRH receptor 1-knockout mice.
In the adult, corticotropin-releasing hormone (CRH) is the key mediator for the behavioural and neuroendocrine response to stress. It has also been hypothesized that, during postnatal development of the stress system, CRH controls the activity of the HPA axis and mediates the effects of early disturbances, e.g. 24 h of maternal deprivation. In the current study we investigated the function of specific brain corticotropin-releasing hormone receptor type 1 (CRHR1) subpopulations in the control of the HPA axis during postnatal development under basal conditions as well as after 24 h of maternal deprivation. We used two conditional CRHR1-deficient mouse lines which lack this receptor, either specifically in forebrain and limbic structures (Cam-CRHR1) or in all neurons (Nes-CRHR1). Basal circulating corticosterone was increased in Nes-CRHR1 mice compared to controls. Corticosterone response to maternal deprivation was significantly increased in both CRHR1-deficient lines. In the paraventricular nucleus, Cam-CRHR1 animals displayed enhanced CRH and decreased vasopressin expression levels. In contrast, gene expression in Nes-CRHR1 pups was strikingly similar to that in maternally deprived control pups. Furthermore, maternal deprivation resulted in an enhanced response of Cam-CRHR1 pups in the brain, while expression levels in Nes-CRHR1 mouse pups were mostly unchanged. Our results demonstrate that brainstem and/or hypothalamic CRHR1 contribute to the suppression of basal corticosterone secretion in the neonate, while limbic and/or forebrain CRHR1 dampen the activation of the neonatal HPA axis induced by maternal deprivation.
Schmidt
M V
MV
Max Planck Institute of Psychiatry, RG Molecular Stress Physiology, Kraepelinstr. 2-10, 80804 Munich, Germany. mschmidt@mpipsykl.mpg.de
Deussing
J M
JM
Oitzl
M S
MS
Ohl
F
F
Levine
S
S
Wurst
W
W
Holsboer
F
F
Müller
M B
MB
de Kloet
E R
ER
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015139:Blotting, Southern; D001923:Brain Chemistry / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D006728:Hormones / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D017403:In Situ Hybridization; D008426:Maternal Deprivation; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D014667:Vasopressins / Q000096:biosynthesis; D000099052:CRF Receptor, Type 1
D006728:Hormones; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D014667:Vasopressins; D000099052:CRF Receptor, Type 1; D004247:DNA; D003346:Corticotropin-Releasing Hormone