Glucocorticoids and serotonin alter glucocorticoid receptor mRNA levels in fetal guinea-pig hippocampal neurons, in vitro
P. Erdeljan A , M. H. Andrews A , J. F. MacDonald A C and S. G. Matthews A B D EA Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 Kings College Circle, Toronto, ON M5S 1A8, Canada.
B Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 Kings College Circle, Toronto, ON M5S 1A8, Canada.
C Department of Pharmacology Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 Kings College Circle, Toronto, ON M5S 1A8, Canada.
D Department of Medicine, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 Kings College Circle, Toronto, ON M5S 1A8, Canada.
E Corresponding author. Email: stephen.matthews@utoronto.ca
Reproduction, Fertility and Development 17(7) 743-749 https://doi.org/10.1071/RD05043
Submitted: 12 April 2005 Accepted: 20 September 2005 Published: 2 November 2005
Abstract
The hypothalamic–pituitary–adrenal (HPA) axis is susceptible to programming during fetal life. Such programming occurs, at least partially, at the level of the hippocampus. The hippocampus plays a central role in regulation of the HPA axis and release of endogenous glucocorticoids, via mediation of glucocorticoid negative feedback. Fetal exposure to synthetic glucocorticoids can permanently alter glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) levels within the hippocampus, and serotonin is thought to be involved in this process. In the present study, we hypothesised that dexamethasone, cortisol and serotonin exposure would modify GR mRNA expression within fetal guinea-pig hippocampal cultures. Cultures were derived from 40-day-old guinea-pig fetuses, and were exposed to 0, 1, 10 and 100 nm dexamethasone, cortisol or serotonin for 4 days. Expression of GR and MR mRNA was examined by in situ hybridisation followed by high-resolution silver emulsion autoradiography. Four-day exposure to dexamethasone (P < 0.05; 100 nm) or cortisol (P = 0.08; 100 nm) downregulated the expression of GR mRNA within neurons. There was no change in the expression of MR mRNA levels following cortisol treatment. Exposure to serotonin (100 nm) significantly increased GR mRNA levels in hippocampal neurons. We conclude that synthetic and endogenous glucocorticoids, as well as serotonin, can influence GR expression during hippocampal development and in this way may act to permanently programme HPA function.
Acknowledgments
This study was supported by the Canadian Institutes of Health Research (MOP-49511) awarded to S.G.M. We wish to thank Ela Czerwinska and Lidia Brandes for their expertise in developing the culture system utilised in this study.
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