Gender-Specific Impact of Sex Hormones on the Immune System

Abstract

Sex hormones are key determinants of gender-related differences and regulate growth and development during puberty. They also exert a broad range modulation of immune cell functions, and a dichotomy exists in the immune response between the sexes. Both clinical and animal models have demonstrated that androgens, estrogens, and progestogens mediate many of the gender-specific differences in immune responses, from the susceptibility to infectious diseases to the prevalence of autoimmune disorders. Androgens and progestogens mainly promote immunosuppressive or immunomodulatory effects, whereas estrogens enhance humoral immunity both in men and in women. This study summarizes the available evidence regarding the physiological effects of sex hormones on human immune cell function and the underlying biological mechanisms, focusing on gender differences triggered by different amounts of androgens between males and females.

Keywords: androgens; estrogens; granulocytes; immune system; lymphocytes; progesterone; sex hormones.

Figure 1

Schematic representation of AR pathway. AR activation by Testosterone, converted to DHT via 5α-reductase causes receptor dimerization and translocation to the nucleus. In the nucleus, AR binds to DNA directly or through cofactors. Eosinophils, DCs, NKs, and both T and B mature lymphocytes do not express AR and the actions of androgens on these cell types are indirectly mediated. Abbreviations: 5α-R, 5α-reductase; AR, androgen receptor; CoF, cofactor; DHT; dihydrotestosterone; P, phosphorylation; SHBG, sex hormone-binding globulin; Testosterone.