Long-term administration of adrenocorticotropin modulates the expression of IGF-I and TGF-beta 1 mRNAs in the rat adrenal cortex.
The effects of long-term adrenocorticotropin (ACTH) therapy on the expression of IGF-I and TGF-beta 1 on rat adrenal cortex was investigated. ACTH (0.1 mg/kg/day) or saline as control was injected intraperitoneally in 5-week-old Wistar rats every day for 4 weeks. ACTH significantly increased adrenal weight (P < 0.05) and serum corticosterone (P < 0.05). Competitive RT-PCR analysis on the adrenocortical mRNA showed increased IGF-I (P < 0.01) at 4 weeks of ACTH and increased TGF-beta 1 (P < 0.01) at 1 week of ACTH compared the control group. ACTH also significantly increased proliferating cell nuclear antigen mRNA level (P < 0.01), at 4 weeks of treatment, which correlated with IGF-I level (P < 0.01), but correlated negatively with ACTH-stimulated TGF-beta 1 level (P < 0.05). There was a weak correlation between IGF-I and serum corticosterone (P < 0.05), and between TGF-beta 1 mRNA levels and serum corticosterone concentration (P < 0.05). Histologically, ACTH induced hypertrophy in the zona fasciculata cells and increased the clear cells containing lipid deposits. Immunohistochemistry showed that IGF-I peptide was mainly expressed in the periphery of the zona fasciculata at 4 weeks of ACTH therapy, while the same therapy caused a slight increase in TGF-beta 1 expression in the same area. Our results show that an increase in adrenocortical growth resulting from ACTH treatment is associated with an increase in IGF-I mRNA expression but only a transient increase in TGF-beta 1 mRNA expression.
Otsuka
F
F
Department of Medicine III, Okayama University Medical School, Japan.
Ogura
T
T
Yamauchi
T
T
Kataoka
H
H
Kishida
M
M
Miyatake
N
N
Mimura
Y
Y
Kageyama
J
J
Makino
H
H
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000311:Adrenal Glands / Q000033:anatomy & histology / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects*; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone