Altered corticosteroid metabolism differentially affects pituitary corticotropin response.

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Hanafusa J, Mune T, Tanahashi T, Isomura Y, Suwa T, Isaji M, Daido H, Morita H, Murayama M, Yasuda K

Altered corticosteroid metabolism differentially affects pituitary corticotropin response.

Am J Physiol Endocrinol Metab. 2002 Feb;282(2):E466-73. doi: 10.1152/ajpendo.00065.2001.

PubMed ID

11788380 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Corticotropin	Cytochrome P450 3A4	Protein	Humans	No	Substrate Inducer	Details