Neuroactive steroids prevent peripheral myelin alterations induced by diabetes.

The effect of the neuroactive steroids progesterone, dihydroprogesterone and tetrahydroprogesterone on myelin abnormalities induced by diabetes was studied in the sciatic nerve of adult male rats treated with streptozotocin. Streptozotocin increased blood glucose levels and decreased body weight gain, parameters not affected by steroids. Streptozotocin increased the number of fibers with myelin infoldings in the axoplasm, 8 months after the treatment. Chronic treatment for 1 month with progesterone and dihydroprogesterone resulted in a significant reduction in the number of fibers with myelin infoldings to control levels. Treatment with tetrahydroprogesterone did not significantly affect this myelin alteration. These results suggest that neuroactive steroids such as progesterone and dihydroprogesterone may represent therapeutic alternatives to counteract peripheral myelin alterations induced by diabetes.

Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats.

Previous studies indicate that steroid hormones may be protective for Schwann cells and promote the expression of myelin proteins in the sciatic nerve of adult rats. In this study, we have evaluated the effect of progesterone (P), dihydroprogesterone (DHP), tetrahydroprogesterone (THP), testosterone (T), dihydrotestosterone (DHT) and 5alpha-androstan-3alpha, 17beta-diol (3alpha-diol) on the morphological alterations of myelinated fibers in the sciatic nerve of 22-24-month-old male rats. The sciatic nerves of untreated old male rats, showed a general disorganization and a significant reduction in the density of myelinated fibers, compared to nerves from 3-month-old male rats. The effect of aging was particularly evident in myelinated fibers of small caliber (<5 microm in diameter). In addition, the sciatic nerves of old rats showed a significant increase in the number of fibers with myelin infoldings in the axoplasm and in the number of fibers with irregular shapes. Treatments of old rats with P, DHP and THP resulted in a significant increase in the number of myelinated fibers of small caliber, a significant reduction in the frequency of myelin abnormalities and a significant increase in the g ratio of small myelinated fibers. Furthermore, P treatment significantly reduced the frequency of myelinated fibers with irregular shapes. In contrast, treatments with T, DHT or 3alpha-diol did not significantly affect any of the morphological parameters examined. In conclusion, our data indicate that P, and its derivatives DHP and THP, are able to reduce aging-associated morphological abnormalities of myelin and aging-associated myelin fiber loss in the sciatic nerve. These data suggest that P, DHP and THP may represent useful therapeutic alternatives to maintain peripheral nerve integrity in aged animals.