Long-term administration of adrenocorticotropin modulates the expression of IGF-I and TGF-β₁ mRNAs in the rat adrenal cortex

The effects of long-term adrenocorticotropin (ACTH) therapy on the expression of IGF-I and TGF-β₁ 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-β₁ (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- β₁ level (P<0.05). There was a weak correlation between IGF-I and serum corticosterone (P<0.05), and between TGF-β₁ 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-β₁ 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-β₁ mRNA expression.