Adrenocortical function in 4-APP treated rats: a coupled stereological and biochemical study

Area of Science:

• Endocrinology
• Biochemistry
• Toxicology

Background:

• 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) is an adenine analogue known to induce lipoprotein deficiency.
• Adrenocortical function and morphology are sensitive to metabolic and toxicological insults.

Purpose of the Study:

• To investigate the effects of 4-APP-induced lipoprotein deficiency on rat adrenocortical function and morphology.
• To correlate biochemical changes in the adrenal gland with quantitative morphologic alterations.

Main Methods:

• Rats were treated with 4-APP to induce lipoprotein deficiency.
• Adrenal glands and livers were analyzed for morphologic and biochemical changes.
• Steroidogenic enzyme activities and hormone concentrations were measured.

Main Results:

• 4-APP treatment enlarged the adrenal cortex and its zona fasciculata and reticularis cells.
• Hepatic triglyceride accumulation and decreased delta 4-steroid hydrogenase activity were observed.
• Serum and adrenal gland cholesterol, triglyceride, and corticosterone levels decreased, but adrenal homogenate corticosterone output increased.
• Enzyme activities (11 beta-hydroxylase, steroid 5 alpha-reductase, neutral lipase) increased per cell, not per tissue weight.

Conclusions:

• 4-APP exerts complex, multidirectional effects on the rat adrenal cortex.
• These effects are likely due to induced lipoprotein deficiency, drug toxicity, stress, and potentially direct actions on the adrenal cortex.