Altered corticosteroid metabolism differentially affects pituitary corticotropin response.
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 corticotropin-releasing factor (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 11 beta-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.
Hanafusa
Junko
J
Third Department of Internal Medicine, Gifu University School of Medicine, Gifu 500-8705, Japan.
Mune
Tomoatsu
T
Tanahashi
Tetsuya
T
Isomura
Yukinori
Y
Suwa
Tetsuya
T
Isaji
Mako
M
Daido
Hisashi
H
Morita
Hiroyuki
H
Murayama
Masanori
M
Yasuda
Keigo
K
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000494:pharmacology; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D006854:Hydrocortisone / Q000493:pharmacokinetics; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D007328:Insulin; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D019695:Glycyrrhizic Acid; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D012293:Rifampin; D003345:Corticosterone; D006854:Hydrocortisone