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Lipopolysaccharide (LPS) is a potent stimulator of the hypothalamic-pituitary-adrenal (HPA) axis. However, the alteration in the HPA axis responsiveness and brain corticosteroid receptor levels during long-term administration of LPS has not been studied well. The present study was designed to examine the effect of single vs. repeated intraperitoneal (i.p.) LPS injection on the HPA axis and brain corticosteroid receptor levels in male Wistar rats. In addition, c-fos mRNA expression was examined in the hypothalamic paraventricular nucleus (PVN) and brainstem catecholaminergic nuclei such as the locus coeruleus (LC) and nucleus tractus solitarius (NTS), the sites known to be involved in LPS-induced HPA axis stimulation. Rats that had received i.p. LPS injection for 6 consecutive days (6-LPS group) had similar levels of plasma adrenocorticotropin (ACTH) and corticosterone (CORT) compared to animals that had received i.p. saline (6-saline group). A single injection of LPS to the 6-saline group (6-saline + challenge) resulted in a substantial increase in plasma ACTH and CORT at 2 h, whereas an additional injection of LPS to the 6-LPS group (6-LPS + challenge) showed less of an increase. As determined by in situ hybridization histochemistry, proopiomelanocortin (POMC) mRNA levels in the anterior pituitary (AP) and corticotropin-releasing hormone (CRH) mRNA levels in the PVN were higher in the 6-LPS than in the 6-saline group. A single injection of LPS to the 6-saline group resulted in a significant increase in AP POMC mRNA and PVN CRH mRNA at 2 h, while injection of LPS to the 6-LPS group showed no additional increase in these levels. C-fos mRNA expression was prominent in the PVN, LC, and NTS following a single injection of LPS, but not following repeated LPS injection. These results suggest that stimulatory input into the PVN decreased following repeated LPS injection. Furthermore, type II glucocorticoid receptor (GR) mRNA levels in the 6-LPS and 6-LPS + challenge groups were decreased in the hippocampus, but not in the PVN or AP. Adrenalectomy with 40% CORT pellet replacement restored ACTH responses following repeated LPS injections to levels similar to those following a single LPS injection. Decreased hippocampal GR mRNA may contribute to the elevated PVN CRH mRNA levels in the 6-LPS group. Nevertheless, inhibition of the pituitary ACTH response by glucocorticoids and reduced hypothalamic drive are partly responsible for decreased pituitary-adrenal responsiveness following repeated LPS injection.
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
March 1995,
The journals of gerontology. Series A, Biological sciences and medical sciences,
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
December 1995,
The European journal of neuroscience,
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
August 1994,
Journal of neuroendocrinology,
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
January 2004,
Psychosomatic medicine,
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
January 1977,
International review of physiology,
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
June 1959,
Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.),
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
January 1972,
Acta physiologica Academiae Scientiarum Hungaricae,
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
August 2001,
Journal of neuroendocrinology,
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
March 2006,
International journal of psychophysiology : official journal of the International Organization of Psychophysiology,
T Takemura, and
S Makino, and
T Takao, and
K Asaba, and
S Suemaru, and
K Hashimoto
November 1967,
Endocrinology,
