*2.8. Thyroid Hormone in Endometrial Receptivity*

Endometrial receptivity is regulated also by thyroid hormone (TH). Both thyroid hormone and thyroid-stimulating hormone receptors (TR and TSHR, respectively) are expressed in the endometrium with variations during the menstrual cycle [190]. Two of the isoforms of TR, TRα1, and TRβ1, are expressed during the mid-luteal phase in glandular and luminal epithelium, showing an increase during the secretory phase, followed by a drastic decrease. Interestingly, the expression of TRα1 and TRβ1, and also of TRα2 and TSHR, in endometrial cells is concomitant to the appearance of the pinopodes and the establishment of endometrial receptivity. The expression of TRα1, TRβ1, TRα2 and also of type 2 deiodinase (DIO2) is regulated by progesterone. In fact, the administration of mifepristrone, an anti-progestinic drug that makes the endometrium unreceptive and induces menstrual bleeding, reduces the expression of TRα1 and TRα2, while it up-regulates TRβ1 and DIO2 expression, suggesting a role for progesterone in regulating molecules involved in TH synthesis and metabolism [191]. The role of TH pathway in endometrial function is also demonstrated by the observation that hypothyroidism is able to reduce uterine endometrial thickness, and also interferes with estrogenic response of the endometrium [192]. TH regulates endometrial receptivity also by acting on LIF pathway, since TSH induces increased expression of LIF and LIF receptor (LIFR) in endometrial stromal cells obtained from human endometrial samples, suggesting a major role for TSH in the implantation process [190].
