Source of high testosterone levels associated with autoimmune ovarian dysgenesis in neonatally thymectomized B6A mice

Thymectomy at three days of age (Tx-3) in mice results in early ovarian dysgenesis and eventual sterility. In (C57BL/6JCr x A/JCr)F1 (B6A) mice, the ovaries are reduced in weight, composed mostly of interstitial-like cells, and are usually devoid of oocytes, follicles, and corpora lutea by 60 days of age. This thymectomy-induced acceleration of follicular atresia is autoimmune in nature and is accompanied by circulating auto-oocyte antibodies (AOA). The dysgenesis is also characterized by elevated levels of testosterone (T). To determine the source of these high T levels, various combinations of Tx-3, and adrenalectomy (Adx) and ovariectomy (Ovx) at 15 days of age were performed. Levels of T, estradiol-17 beta (E2), and corticosterone (B) were analyzed and compared with ovarian morphology. Except for plasma B levels, animals that underwent both Tx-3 and Adx were not significantly different from mice that received Tx-3 alone. As anticipated, B and E2 levels were substantially decreased in Adx and Ovx mice, respectively. T levels in the Tx-3 and Tx-3/Adx groups were first elevated at 60 days of age (0.17 and 0.14 ng/ml, respectively) then rose sequentially through 150 days of age (0.91 and 0.89 ng/ml, respectively) as compared to the significantly lower T levels in intact and Tx-3/Ovx mice (less than 0.20 ng/ml through 150 days of age). These results suggest that the increased T is being secreted by ovarian rather than adrenal tissue. Furthermore, this model may be of value to investigators interested in the study of interstitial or non-follicular steroidogenesis in the ovary.