Adrenocorticotropic hormone (ACTH) increases the expression of its own receptor gene.
Regulation of the ACTH receptor (R) in the adrenal gland by its own ligand "ACTH" has been a matter of controversy. In the present study, whether ACTH regulates the expression of mRNA for its own receptor in the adrenal gland was studied in human subjects and in rats in vivo. In the human study, adrenal adenoma tissues as well as adjacent normal tissues were obtained at surgery from two patients with typical Cushing's syndrome. Northern blot analysis revealed two ACTH-R mRNA species with 4.0 kb and 2.0 kb. ACTH-R mRNAs in the adenoma tissues were much more abundant than those in the normal tissues from the two patients, suggesting that the mRNA in normal adrenal tissue is either suppressed by cortisol excess or the absence of ACTH. To examine the mechanism involved in ACTH-R mRNA regulation, the changes in the receptor mRNA caused by ACTH were studied in dexamethasone-treated rats. Administration of dexamethasone for 5 days resulted in a marked decrease in ACTH-R mRNA to an undetectable level. A bolus administration of ACTH1-24 intravenously or ACTH-Z1-24 intramuscularly to the dexamethasone-treated rat did not cause any significant change in ACTH-R mRNA from 0.5 to 12 h after the administration. However, a significant increase in the receptor mRNA was observed at 24 h after the ACTH-Z1-24 and the level was further increased until 48 h followed by a sustained increase at 72 h when it was given once every 24 h. These data suggest that the ACTH-receptor is increased by ACTH at a pretranslational level.(ABSTRACT TRUNCATED AT 250 WORDS)
Morita
T M
TM
Department of Endocrinology and Metabolism, Nagoya University, Japan.
Imai
T
T
Murata
Y
Y
Kambe
F
F
Funahashi
H
H
Takagi
H
H
Seo
H
H
D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D000328:Adult; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003480:Cushing Syndrome / Q000188:drug therapy / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018043:Receptors, Corticotropin / Q000235:genetics* / Q000378:metabolism
D005938:Glucocorticoids; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone