Long-term administration of hydrocortisone: down-regulating the level of cytokine and resulting in injuring testicular tissue of juvenile mice.

Abstract

Background: As an important glucocorticosteroid hydrocortisone has been widely used in clinical practice. Even though a series of side effects induced by long-term administration of hydrocortisone are known, but side effects related to testicular injury of juvenile mice are still unknown. Here we explored the damage of the testicular tissue of male juvenile mice induced by long-term administration of hydrocortisone.

Methods: To damage the testicle, male ICR juvenile mice were orally given hydrocortisone (69 µmol/kg/day, once a day for 16 consecutive days) for establishing mouse testicular injury model. To get normal testicle, male ICR mice were orally given CMC-Na (10 mL/kg/day, once a day, for 16 consecutive days). The morphological change was shown by the testicular interstitium and seminiferous tubules, as well as the number of the spermatogenic cells. To get insight into the potential mechanism of damaging testicular tissue the level of IL-2, IL-6 and TNF-α of the corresponding samples were tested by ELISA experiment.

Results: Long-term use of hydrocortisone resulted in a number of changes, such as the damage of testicular tissue, the decreasing of the number of spermatogonia in all three phases, a selective effect on spermatocytes in proliferative phase only, the decreasing of the number of sperm cells in all three phases, the down regulation of IL-2, IL-6 and TNF-ɑ both in the serum and testicular tissue of male juvenile mice.

Conclusions: Hydrocortisone is widely used to treat a series of diseases clinically, and some side reactions are well known. To the best of our knowledge, testicular injury for male juvenile mice was a newly founded side reaction caused by long-term administration of hydrocortisone. Moreover, the decrease of serum level of IL-2, IL-6 and TNF-ɑ could be the molecular mechanism, and may be used as potential biomarker to monitor the progression of testicular injury for male adolescent patients of receiving long-term hydrocortisone. Avoiding testicular damage is crucial for male adolescent patients receiving hydrocortisone, and the finding is of importance for improving the clinical applications of hydrocortisone.