Beta-endorphin inhibits hypoglycemia-induced gene expression of corticotropin-releasing factor in the rat hypothalamus.
Endogenous opioid peptides have a role in the regulation of the hypothalamic-pituitary-adrenal axis. Recently, beta-endorphin (EP) has been thought to inhibit CRF release in vivo and in vitro. In the present study we examined the effects of central administration of EP on ACTH secretion and gene expression of both CRF in the hypothalamus and POMC in the anterior pituitary gland (AP) during basal and insulin-induced hypoglycemia in pentobarbital-anesthetized rats. Administration of EP in the lateral ventricle decreased basal CRF levels in the median eminence and inhibited basal and hypoglycemia-induced ACTH secretion in a dose-dependent manner. Hypoglycemia-induced POMC mRNA levels in the AP and CRF mRNA levels in the hypothalamus were also dose-dependently inhibited by the administration of EP. The inhibitory effect of EP was reversed by naloxone. These results suggest that 1) central administration of EP acts through the opioid receptor to inhibit hypoglycemia-induced CRF gene expression in the hypothalamus and CRF release, which results in a decrease in ACTH secretion and POMC mRNA levels in the AP; and 2) the active site of EP is the CRF neuron in the paraventricular nucleus.
Suda
T
T
Department of Medicine, Tokyo Women's Medical College, Japan.
Sato
Y
Y
Sumitomo
T
T
Nakano
Y
Y
Tozawa
F
F
Iwai
I
I
Yamada
M
M
Demura
H
H
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D015152:Blotting, Northern; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000097:blood / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D007003:Hypoglycemia / Q000503:physiopathology*; D007031:Hypothalamus / Q000737:chemistry* / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D010903:Pituitary Gland, Anterior / Q000737:chemistry; D011333:Pro-Opiomelanocortin / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D012333:RNA, Messenger; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone