Abstract
Hyperprolactinemia (hyperPRL) related hypogonadism is caused by either a suppressed hypothalamic function by PRL or by a direct inhibitory influence of PRL on the Leydig cells. However, the phenomenon is associated with the interaction of the testicular interstitial macrophages. PRL challenges the macrophages to release TNF-α, which consequently intervenes the function of Leydig cells and their testosterone (T) secretion. This study is to test the hypothesis that adding TNF-α antibody or TNF-α antagonist can counteract the detrimental effects of PRL on T release by the Leydig cells under the status of hyperPRL. Animal studies and in vitro cell cultures. HyperPRL was induced by transplantation of 2 ectopic anterior pituitary glands to the space under the renal capsule. The control groups were transplanted with an equal amount of brain cortex. Six weeks after the surgery, the male Spraque-Dawley rats were sacrificed and the testicular interstitial cells (TICs) were isolated. The TICs were treated with human chorionic gonadotropin (hCG, 0.05 IU/ml) and ovine PRL (o-PRL) with or without the presence of TNF-α antibody or TNF-α antagonist Etanercept. The incubating time was 1h and the medium was collected for T measurement by radioimmunoassay. Under the challenge of hCG, the more o-PRL added, the more significantly the suppression of T release from the TICs. After the TNF-α antibody or TNF-α antagonist Etanercept were added, the phenomenon of suppression of T release was reversed. It showed a dose-dependent relationship. At this circumstance, o-PRL becomes a boosting aid on T release to hCG challenge. While incubating the Leydig cells alone (with the macrophages removed) with o-PRL, the inhibitory effects of PRL to T release were replaced with stimulatory effects. The results indicate that the detrimental effects of hyperPRL on testicular T release are due to the influence of testicular interstitial macrophages through the action of TNF-α that in term hampering the Leydig cells’ response to hCG. The effects are potentially reversible by manipulating the actions of TNF-α.
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