Adrenalectomy Does Not Block the Inhibition of Mammary Carcinogenesis by Dietary Energy Restriction in Rats

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Abstract
Dietary energy restriction (DER) has been shown to reproducibly inhibit chemically induced mammary carcinogenesis. The inhibitory activity of DER has been reported to be associated with an increase in circulating corticosterone as well as a decrease in insulin-like growth factor 1 (IGF-1). To determine whether the adrenal glands are required for cancer inhibitory activity, the effects of DER were investigated in adrenalectomized (ADX) rats. Female Sprague-Dawley rats, 29–31 per group, were injected with 0.05 g 1-methyl-1-nitrosourea/kg body wt at 21 d of age, sham operated (SHAM) or bilaterally ADX at 24 d of age, and after 3 d adapted to meal feeding during which rats ate ad libitum (AL) or were restricted to 60% of AL energy intake. ADX resulted in a marked reduction in serum corticosterone in both AL and DER rats. Whereas the carcinogenic response in the mammary gland was not statistically different in SHAM-AL and ADX-AL rats, ADX did not block the cancer inhibitory activity of DER. In fact, cancer inhibitory activity was greatest in ADX-DER rats. Circulating levels of glucose, insulin, IGF-1, and IGF binding protein 3 also were reduced in DER rats. Collectively, these findings indicate that adrenal glands are not required for manifestation of the cancer inhibitory activity of DER. If circulation-borne factors such as corticosterone or IGF-1 are involved in the inhibition of mammary carcinogenesis by DER, IGF-1 is likely to play a greater role than corticosterone.

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