Related Experiment Videos
Brain corticosteroid receptor gene expression and neuroendocrine dynamics during aging
J A van Eekelen1, N Y Rots, W Sutanto
1Division of Medical Pharmacology, University of Leiden, The Netherlands.
The Journal of Steroid Biochemistry and Molecular Biology
|January 1, 1991
Summary
Aging alters stress response by reducing corticosteroid receptors in the brain and pituitary, affecting hypothalamic-pituitary-adrenal axis function in rats. This suggests changes in receptor processing, not gene expression, during senescence.
Area of Science:
- Neuroendocrinology
- Aging Research
- Molecular Biology
Background:
- The hypothalamic-pituitary-adrenal (HPA) axis regulates stress response.
- Corticosteroid receptors, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), play crucial roles in HPA axis feedback.
- Age-related changes in receptor function may impact stress responsiveness.
Purpose of the Study:
- To investigate the age-related changes in HPA axis stress responsiveness.
- To examine the relationship between corticosteroid receptor properties and HPA axis function in aged rats.
- To determine if changes in receptor number or gene expression are responsible for altered stress response in senescence.
Main Methods:
- Comparison of young (3 months) and old (30 months) male Brown Norway rats.
- Measurement of circulating ACTH and corticosteroid levels under basal and stress conditions.
- Quantification of MR and GR binding in the hippocampus, hypothalamus, and pituitary.
- Assessment of MR and GR mRNA levels using in situ hybridization.
Main Results:
- Old rats exhibited elevated circulating ACTH levels under basal and stress conditions compared to young rats.
- A reduction in MR binding in the hippocampus and GR binding in the hypothalamus and pituitary was observed in old rats.
- These receptor binding changes correlated with enhanced neuroendocrine responsiveness and feedback following stress.
- Changes in receptor binding did not align with MR and GR mRNA levels, indicating post-transcriptional regulation.
Conclusions:
- Aging significantly impacts the neuroendocrine stress response in rats.
- Reduced corticosteroid receptor binding in key brain regions and the pituitary is associated with altered HPA axis function in senescence.
- The findings suggest that post-transcriptional modifications, rather than altered gene expression, are primarily responsible for changes in corticosteroid receptor availability during aging.