Androgens are neuroprotective in the dentate gyrus of adrenalectomized female rats

Neuroprotective effects of androgens have not been well-characterized, but there is evidence that 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) has anti-seizure effects. To further examine androgens' neuroprotective effects, testosterone (T), dihydrotestosterone (DHT), 3 alpha-diol (1.0 mg/kg SC daily), or sesame oil vehicle was administered to adrenalectomized or sham-operated, young, female Long Evans rats (N = 52). After seven days, animals were perfused and trunk blood was collected for radioimmunoassay of plasma corticosterone and androgens. No pyknotic cells were seen in the dentate of the sham-operated animals or those animals that had incomplete adrenalectomies (n = 20); however, cresyl violet and TUNEL stains revealed pyknotic cells in the granule layer of the dentate gyrus of adrenalectomized rats (n = 28). Testosterone, DHT, or 3 alpha-diol significantly reduced the number of pyknotic cells in the dentate gyrus compared to vehicle administered, adrenalectomized rats. Steroid-administered animals had levels of T, DHT, or 3 alpha-diol within physiological concentrations. These findings suggest that T, DHT, or 3 alpha-diol may have neuroprotective effects via a common mechanism of action.