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RasGRF1 regulates the hypothalamic-pituitary-adrenal axis specifically in early-adolescent female mice.
- Source :
-
The Journal of endocrinology [J Endocrinol] 2015 Oct; Vol. 227 (1), pp. 1-12. Date of Electronic Publication: 2015 Aug 05. - Publication Year :
- 2015
-
Abstract
- Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the induction and prolongation of a variety of psychiatric disorders. As such, much effort has been made to understand the molecular mechanisms involved in its control. However, the vast majority of the studies on the HPA axis have used adult animals, and among these the majority has used males. Here we show that in knockout mice lacking the guanine nucleotide exchange factor, RasGRF1, habituation to 30 min/day of restraint stress is markedly accelerated, such that these mice do not display elevated corticosterone levels or enhanced locomotion after 7 days of stress exposure, like WT mice do. Strikingly, this phenotype is present in early-adolescent female RasGRF1 knockout mice, but not in their early-adolescent male, mid-adolescent female, adult female or adult male counterparts. Moreover, not only is there a clear response to restraint stress in early-adolescent female RasGRF1 knockout mice, their response after one, three and five exposures is magnified approximately threefold compared to WT mice. These findings imply that distinct mechanisms exist to regulate the HPA axis in early-adolescent females that involves RasGRF1. A full understanding of how RasGRF1 controls the HPA axis response to stress may be required to design effective strategies to combat stress-associated psychiatric disorders initiated in young females.<br /> (© 2015 Society for Endocrinology.)
- Subjects :
- Age Factors
Animals
Behavior, Animal
Corticosterone blood
Female
Habituation, Psychophysiologic
Hypothalamo-Hypophyseal System growth & development
Hypothalamo-Hypophyseal System physiology
Hypothalamo-Hypophyseal System physiopathology
Male
Mice, Inbred C57BL
Mice, Knockout
Pituitary-Adrenal System growth & development
Pituitary-Adrenal System physiology
Pituitary-Adrenal System physiopathology
Restraint, Physical
Sex Characteristics
Stress, Physiological
Stress, Psychological blood
Stress, Psychological metabolism
Stress, Psychological physiopathology
Time Factors
ras-GRF1 genetics
Hypothalamo-Hypophyseal System metabolism
Pituitary-Adrenal System metabolism
ras-GRF1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1479-6805
- Volume :
- 227
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 26246084
- Full Text :
- https://doi.org/10.1530/JOE-15-0304