96. Adrenocortical regeneration following complete adrenalectomy

Abstract

Laboratory rodents undergoing bilateral adrenalectomy (ADX) are commonly maintained under corticosterone replacement regimens. A prolonged study we conducted, where ADX F344 rats were not supplemented with corticosterone, surprisingly revealed moderate endogenous corticosterone levels (50–250 ng/ml), rather than the expected near-zero levels. Therefore, we systematically studied potential alternative sources of corticosterone in adult ADX male and female F344 and male Lewis rats (n = 52). Histological analysis confirmed complete excision of adrenals. Blood was withdrawn 2, 6, and 12 weeks following ADX, and baseline and restraint stress levels of corticosterone were assessed during the light and dark phases. At 2 weeks following ADX, rats exhibited near-zero levels of corticosterone, which did not increase during the dark phase or following stress. However, at 6 and 12 weeks following ADX, all rats doubled and quadruple their corticosterone levels, exhibiting significant circadian rhythm and stress responses, reaching 400 ng/ml in F344 ADX females (75% of sham-operated control levels), and consuming water, rather than saline. MRI imaging revealed an adrenal-like tissue in some ADX rats near the original adrenal location. Preliminary histologic analysis identified a regenerated a-typical adrenocortical structure without zonal compartments, which released ample amount of corticosterone in vitro. These findings correspond with anecdotal clinical reports. We hypothesize that high ACTH levels following ADX stimulate stem/progenitor cells to differentiate and form functional adrenal-like tissue. A third replicate study is ongoing.