Endocrine Abstracts

Adrenal steroids and alterations in steroid metabolism are important factors in the development of obesity in Zucker rats. One might predict, therefore, that the function of the adrenal gland differs between lean and obese Zucker animals. Accordingly, we investigated adrenal gland morphology and function and have considered not only glucocorticoids and HPA activity but also the renin-angiotensin-aldosterone system. Plasma samples and adrenal glands were obtained from young 12 week old rats, at a stage when obesity is becoming apparent. Adrenals (n=6) were either fixed and stained for morphology or were used to measure gene expression by a real time PCR method. The size of corticosterone-synthesizing cells was increased in glands of obese compared with lean rats; inner and outer zona fasciculata and zona reticularis cells were 15–30% larger (P<0.05). In contrast, the cells of the aldosterone-synthesizing zona glomerulosa were 15% smaller (P<0.02). This pattern of difference was even more marked in adrenals from older animals where obesity was fully established. The morphological differences between adrenals from lean and obese rats were compatible with functional changes. Plasma corticosterone and ACTH concentrations were elevated in obese rats and expression of adrenal CYP11B1, the gene encoding 11β- hydroxylase, the final enzyme in corticosterone biosynthesis, was increased (P<0.01). The expression of CYP11B2, the gene encoding aldosterone synthase, was decreased and plasma renin activity, a major determinant of zona glomerulosa hypertrophy and hyperplasia was reduced (P<0.01). However, plasma aldosterone concentration was higher in obese compared with lean rats (P<0.05). These observations of increased mineralocorticoid and glucocorticoid hormone activity, differential effects on adrenocortical zonation and suppression of renin activity are similar to those we and others have made concerning the effects of chronic ACTH excess. We conclude that increased adrenocortical activity may contribute to the hypertension that we have observed in obese Zucker rats.