A study on the Possible Pro-inflammatory Effects Promoted by Thyroid Hormone on the Adult Female Albino Rat Ovaries

Background: Hyperthyroidism is a widespread endocrine disorder commonly associated with variable pathophysiologic consequences. In fact, the link between thyroid disturbances and female reproduction has long been documented. In addition, it has become increasingly accepted that chronic hyperthyroidism is linked to an increased incidence of carcinogenesis, including ovarian cancer. Cyclooxygenase-2 (COX2) has been shown to be associated to a great extent with inflammation and tumor pathology. In addition both estrogen receptor (ER) and thyroid receptor (TR) may exhibit cross talk with each other and were frequently linked to carcinogenesis ,also progesterone and its receptor (PR) was reported to be generally protective against some pathologic conditions and cancers. Based on previous concepts, the preseht study aimed to clarify whether hyperthyroidism is associated with an inflammatory state in the female rat ovary , also to examine the effects of estrogen receptor modulation using tamoxifen treatment. In addition , we also tried to testify the ability of progesterone treatment to act as an anti-inflammatory agent on the ovary. Methods : Forty -eight adult female albino rats were divided into eight groups (n=6/group) Jour normal groups (I, 2, 3, and 4), and four hyperthyroid groups (5, 6, 7, and 8) in which hyperthyroidism was induced , tamoxifen was given to groups 2, 4, 6, and 8 . Whereas progesterone was given to groups 3, 4, 7, and 8. Results: It was clear that, thyroxine administration in our study was associated with the highest levels of TR, COX2, and ER, as well as the lowest levels of PR expression among all studied groups. Both tamoxifen and progesterone treatment were found to lower COX2, as well as TR and ER expression in hyperthyroid rats. There was also upregulation of PR expression in the hyperthyroid animals treated with tamoxifen and/or progesterone. However, it seemed that combined administration is not essentially more powerful than giving progesterone alone since the results in the hyperthyroid rats receiving both tamoxifen and progesterone were not significantly different from the results of those receiving progesterone alone. Furthermore, the results of the hyperthyroid rats have shown progesterone to be more effective than tamoxifen in controlling the pro-inflammatory gene profile. Conclusion: Induced hyperthyroidism in rats may be associated with a chronic inflammatory state in the ovarian tissue, which may eventually predispose to cancer. Administration of progesterone and/or tamoxifen appears to be protective, since our results further clarified the protective role of tamoxifen in the ovarian tissue as well as confirming the antiinflammatory impact associating progesterone treatment on the rat ovary.