The compensatory expression of reproductive hormone receptors in the thymus of the male rat following active immunization against GnRH

Abstract: To determine whether hormone-receptor signaling pathways in the thymus are altered by active immunization against gonadotrophin-releasing hormone I (GnRH), 3-week-old Sprague–Dawley male rats received GnRH-tandem-OVA peptides (200μg/ml), and the effects were compared to a control group. Serum testosterone, LH and FSH concentrations were markedly reduced, with severe testicular atrophy, compared to controls, demonstrating effective blockade of the pituitary–gonadal axis. The reduction in LH and FSH concentrations in the thymus of immunized animals was lower than that observed in the serum, where a significant difference (P <0.001) in concentration was observed between both groups. Concentrations of GnRH were increased in the thymus of immunized rats. In thymic tissue, GnRHR, FSHR and LHR demonstrated stronger immunostaining, and AR weaker staining, in the immunized group compared to controls. Reproductive hormone receptor mRNA expression was consistent with protein variations in the immunized thymus. Compared to controls, GnRHR gene levels were significantly increased (P <0.05), however, AR mRNA expression were greatly decreased with immune week-age (P <0.05). Both FSHR and LHR mRNA expression levels were significantly higher in the treated group than in controls in the first three samples (P <0.05). When GnRHR was blocked by an antagonist in thymocytes, all reproductive hormone receptor gene expressions were significantly increased (P <0.001). In summary, these findings suggest that active immunization against GnRH can up-regulate GnRH receptor and gonadotropin receptor signaling, by stimulating thymic autocrine and paracrine function, whereas the androgen receptor is down-regulated due to a lack of testosterone secretion in the thymus. [Copyright &y& Elsevier]