RasGRF1 regulates the hypothalamic–pituitary–adrenal axis specifically in early-adolescent female mice
| Autor: | Beverly S. Rubin, Larry A. Feig, Shan-Xue Jin, Christopher Bartolome, Belkis Gizem Uzturk |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Restraint Physical Hypothalamo-Hypophyseal System medicine.medical_specialty Time Factors Endocrinology Diabetes and Metabolism Pituitary-Adrenal System Biology Article chemistry.chemical_compound Endocrinology Ras-GRF1 Stress Physiological Corticosterone Internal medicine medicine Animals Habituation Habituation Psychophysiologic Mice Knockout Sex Characteristics Behavior Animal ras-GRF1 Age Factors Phenotype Mice Inbred C57BL medicine.anatomical_structure chemistry Knockout mouse Female Guanine nucleotide exchange factor Stress Psychological Hypothalamic–pituitary–adrenal axis Sex characteristics |
| Zdroj: | Journal of Endocrinology. 227:1-12 |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1530/joe-15-0304 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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