Thyroid hormone receptors and ligand, tissue distribution and sexual behavior

The thyroid hormones (THs) triiodothyronine (T3) and tetraiodothyronine, or thyroxine (T4), not only dramatically impact on development and differentiation, but also on the sexual and reproductive function. There is large body of literature, in fact, on the effects of THs on the reproductive function in both humans (Poppe and Velkeniers, 2004; Wajner et al., 2009) and animals (Hapon et al., 2010; Nelson et al., 2011). For a long time the gonads were thought to be unresponsive to THs, but TH receptors (TR) were discovered in rat (Jannini et al., 1990; Palmero et al., 1988) and then in human testis (Jannini et al., 2000). In women, the association of menstrual disturbance with thyroid disease was described as early as 1840 by von Basedow, but the discovery of TRs in the ovary was carried out at the end of last century (Wakim et al., 1994b). Therefore, the link between thyroid and reproductive function was well established. Since then, research has shown that thyroid dysfunction is associated with an adverse effect on fertility, both in men (Wagner et al., 2009) and women (Dittrich et al., 2011). There is also evidence that THs can affect the sex steroid hormone axis (Bagamasbad and Denver, 2011), consequently sexual hormones and the pituitary gland can mediate the action of THs on the reproductive physiology. While the effects of THs on fertility have been widely studied, little is known about their influence on sexual function. In the last few years, an increasing number of evidences have shown the influence of THs on male sexual function, particularly on ejaculation control as well on desire and erectile function (Carani et al., 2005; Corona et al., 2012b; Di Sante et al., 2016). The female sexual function and the relationship with thyroid function is still less studied. Furthermore, studies conducted on animals have shown the presence of TRs in the male (Carosa et al., 2010) and female genitalia (Rodriguez-Castelan et al., 2017). Moreover, knockout mice for TRs showed alterations in sexual behavior (Dellovade et al., 2000). The purpose of this review is to summarize and discuss the available data on the influence of THs on male and female sexual function to understand the molecular mechanisms of the influence of the thyroid gland on sexual behavior and function.