The Effect Of Estrogen And Prolactin On The Induction Of Experimental Autoimmune Thyroiditis

Many observations proposed that there is a significant gender differences inthe incidence of autoimmune diseases, furthermore, a disproportionate number is women. The predominance of autoimmune diseases among women suggests that the lelve of sex hormone, especially estrogen, may modulate susceptibility. Autoimmune thyroid diseases also have the gender gap. In human chronic (Hashimoto's) thyroiditis, the female to male ratio is 4:1-19:1. Estradiol-17p(E2-17p) and prolactin(PRL) are two important hormones in female. To elucidate the role of estrogen in the pathogenesis of autoimmune thyroid diseases, we observed and studied the effect of the two hormones on the modulation of immune responses Such studies may have implications for clinical medicine. In this study, ten-week old ovariectomized(OVX) female rats were induced experimental autoimmune thyroiditis(EAT) by immunization with thyroglobulin(Tg) from SD rats in the presence of complete Freund's adjuvant(CFA). Thyroiditis was pathologically evaluated by HE staining. The level of E2-17B and PRL were measured by RIA; anti-Tg antibody was detected by ELISA and IFN-r, IL-10 mRNA in thyroid gland were assayed by RT-PCR. The results suggested that high liter of anti-Tg was presented in the EAT groups, while the OVX group showed a significant reduction in the thyroid pathology and incidence of EAT. Meanwhile, the level of E2-170 and PRL were much lower in OVX rats than that in intact rats followed by the decrease in IFN-y mRNA and the increase in IL-10 mRNA.As a result of the decrease in serum levels of estradiol-17(J and prolactin, it was proposed that the balance of IFN-y and IL-10 was necessary for the induction of EAT. Whereas, OVX resulted in the consistent decreased production of the two hormones, so it was questioned whether prolactin had direct function on EAT or coordinated with E2-170. In Part two, through the intervene of PRL production by bromocriptine(BRC), we further studied the effect of prolactin on the induction of EAT. The results indicated that the incidence and severity of EAT were much lower in the group treated with BRC than in the group without treatment by BRC BRC inhibiting secretions of prolactin in the pituitary, decreased the expression level of IL-2/IL-2R mRNA in spleen. Prolactin stimulating the expression of IL-2/IL-2R mRNA, exerts a direct stimulatory effect on the immune response thereby, the enhancement of cell and humoral-based immunity will play an important function on the induction of EAT.Conclusion: As two important hormones in female, estrogen and prolactin have a reciprocal endocrinologic relationship and both hormones participate the modulation of immune system and expression of many cytokines. As a result, they play important roles on the induction of EAT. Further investigation into actions and interactions of estrogen and prolactin with autoimmunity will provide a better understanding of the female preponderance of autoimmunity and facilitate a more rational approach to hormonal immunotherapy.