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Am J Physiol Endocrinol Metab (October 2, 2001). doi:10.1152/ajpendo.00065.2001
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Articles in PresS, published online ahead of print October 2, 2001
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00065.2001
Submitted on February 20, 2001
Accepted on September 27, 2001

Altered Corticosteroid Metabolism Differentially Affect Pituitary Corticotropin Response

Junko Hanafusa1, Tomoatsu Mune1*, Tetsuya Tanahashi1, Yukinori Isomura1, Tetsuya Suwa1, Mako Isaji1, Hisashi Daido1, Hiroyuki Morita1, Masanori Murayama2, and Keigo Yasuda1

1 Third Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan
2 Internal Medicine, Gifu Prefectural Hospital, Gifu, Japan

* To whom correspondence should be addressed. E-mail: mune{at}cc.gifu-u.ac.jp.

To evaluate the effects of altered corticosteroid metabolism on the hypothalamic-pituitary-adrenal axis, we examined rats treated with glycyrrhizic acid (G-rats) or rifampicin (R-rats) for 7 days. The half-life of exogenously administered hydrocortisone as a substitute for corticosterone was longer in G-rats and shorter in R-rats with no differences in basal plasma levels of ACTH or corticosterone. The ACTH responses to human CRF or insulin-induced hypoglycemia were greater in G-rats and tended to be smaller in R-rats compared with those in the control rats, whereas the corticosterone response was similar. No difference was observed in the content and mRNA level of hypothalamic CRF among the groups. The number and mRNA level of CRF receptor and type 1 11ß-hydroxysteroid dehydrogenase (11-HSD1) mRNA level in the pituitary were increased in G-rats but not changed in R-rats, suggesting that chronically increased intrapituitary corticosterone upregulates pituitary CRF receptor expression. In contrast, CRF mRNA levels in the pituitary were increased in R-rats. Our data indicate novel mechanisms of corticosteroid metabolic modulation and the involvement of pituitary 11-HSD1 and CRF in glucocorticoid feedback physiology.






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