Comparison of central corticosteroid receptor expression in male Lewis and Fischer rats

The histocompatible inbred Lewis (LEW) and Fischer (F344) rat strains exhibit marked phenotypic differences in the hormonal activity of the hypothalamic-pituitary-adrenal (HPA) axis. As such they provide an important comparative model for the study of HPA regulation including the central feedback regulation by the glucocorticoid transcription factors, the mineralocorticoid receptor (MR) and the glucocortiocoid receptor (GR). In adult male rats, basal nadir plasma corticosterone values were similar in the two strains whereas the amplitude and duration of the corticosterone response to restraint were significantly reduced in LEW. MR and GR mRNA expression were compared in LEW and F344 throughout the rostrocaudal extent of the hippocampus. Hippocampal MR expression was consistent throughout the rostrocaudal extent and similar in F344 and LEW males. Hippocampal GR expression was consistent throughout the rostrocaudal extent, but significantly greater in the rostral dentate gyrus and Cornu ammonis subfields in LEW males compared with F344 males. The LEW phenotype of relatively high hippocampal GR expression and HPA hypoactivity is shared by outbred rats exposed to neonatal handling and GR-overexpressing transgenic mice. Whether or not this relationship is causal, as well as the functional significance of the rostral-extent specific GR difference, remains to be elucidated.