The effects of anti-TNF-α antibody on hyperprolactinemia-related suppression of hCG-induced testosterone release in male rats.

INTRODUCTION

Hyperprolactinemia (hyperPRL)-related hypogonadism or suppression of human chorionic gonadotropin (hCG)-induced testosterone (T) release is hypothesized to be mediated by a testicular interstitial macrophage and tumor necrosis factor alpha (TNF-α)-involved blockage.

AIM: To test if the lower T response after hCG challenge in the hyperPRL rats is reversed by administrating anti-TNF-α antibody (Ab).

METHODS

HyperPRL was induced by allografting two anterior pituitary (AP) glands per rat. Control rats were grafted with similar amount of cerebral cortex. The testicular interstitial cells (TIC) were isolated from the testis 6 weeks after grafting. TIC was treated with anti-TNF-α Ab with or without hCG. The other groups of rats received intra-testicular or intra-muscular anti-TNF-α Ab 7 days before in vitro study. The TIC isolated from each testis was incubated and T release with or without hCG challenge were measured.

MAIN OUTCOME MEASURES: Prolactin (PRL) and T were measured by radioimmunoassay. TNF-α was measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS

When low dose of anti-TNF-α Ab was administered to the TIC incubation, the effects of PRL-related suppression of hCG-stimulated T release were not significant. While a higher dose of anti-TNF-α Ab almost abolished the suppressive effects of PRL to hCG-stimulated T release. Prior intra-testicular or intra-muscular administration of anti-TNF-α Ab reversed the suppressive effects of AP grafting on TIC's T release. This was demonstrated in groups with anti-TNF-α Ab injection both 7 and 1 day prior to TIC incubations.

CONCLUSIONS

The data support the hypothesis that the suppression of hCG-induced T release associated with hyperPRL is through a TNF-α-mediated mechanism to suppress the Leydig cells. The effect of anti-TNF-α Ab is durable for at least 7 days. Besides intra-testicular injection, there might be other ways available for administrating Ab. Anti-TNF-α Ab has a potential therapeutic application on hyperPRL-induced hypogonadism or suppression of hCG-induced T release.