Effects of repetitive administration of recombinant human interleukin-1 beta, an analog or corticotropin-releasing hormone combined with lysine vasopressin on rats with glucocorticoid-induced secondary adrenocortical insufficiency.
We investigated effects of corticotropin-releasing hormone (CRH), lysine vasopressin and interleukin (IL)-1 beta[1-148], a less pyrogenic analog of human IL-1 beta, on the hypothalamo-pituitary-adrenal axis in a rat model of secondary adrenocortical insufficiency. After 2 weeks of corticosterone 21-sodium succinate treatment, hypothalamic CRH, anterior pituitary adrenocorticotropic hormone (ACTH) and the adrenal weight of the rats decreased significantly and their plasma ACTH showed a significantly smaller response to ether stress, as did plasma corticosterone level. A mixed solution of CRH (10 micrograms) and lysine vasopressin (2 micrograms) or recombinant human IL-1 beta[1-148] (1 micrograms), administered to these rats for 7 days, apparently accelerated the recovery of the pituitary and adrenocortical responsiveness to ether stress and significantly increased the recovery rate of anterior pituitary ACTH contents and adrenal weight. The IL-1 beta analog also increased hypothalamic CRH. These data indicated that, in a rat model with glucocorticoid-induced adrenocortical insufficiency, synthesis and release of hypothalamic CRH, pituitary ACTH and adrenal glucocorticoid were all considerably affected. CRH combined with lysine vasopressin or a less pyrogenic IL-1 beta analog, when administered to these rats, accelerated the recovery of the pituitary and the adrenocortical functions significantly, suggesting the potential clinical usefulness of these peptides.
Murakami
N
N
Department of Medicine, Kyoto University Faculty of Medicine, Japan.
Fukata
J
J
Usui
T
T
Naito
Y
Y
Tominaga
T
T
Nakai
Y
Y
Masui
Y
Y
Nakao
K
K
Imura
H
H
D000309:Adrenal Insufficiency / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008236:Lypressin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D005938:Glucocorticoids; D007375:Interleukin-1; D011994:Recombinant Proteins; D008236:Lypressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone