Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung

Abstract

Androgens, the predominant male sex hormones, drive the development and maintenance of male characteristics by binding to androgen receptor (AR). As androgens are systemically distributed throughout the whole organism, they affect many tissues and cell types in addition to those in male sexual organs. It is now clear that the immune system is a target of androgen action. In the lungs, many immune cells express ARs and are responsive to androgens. In this review, we describe the effects of androgens and ARs on lung myeloid immune cells-monocytes and macrophages-as they relate to health and disease. In particular, we highlight the effect of androgens on lung diseases, such as asthma, chronic obstructive pulmonary disease and lung fibrosis. We also discuss the therapeutic use of androgens and how circulating androgens correlate with lung disease. In addition to human studies, we also discuss how mouse models have helped to uncover the effect of androgens on monocytes and macrophages in lung disease. Although the role of estrogen and other female hormones has been broadly analyzed in the literature, we focus on the new perspectives of androgens as modulators of the immune system that target myeloid cells during lung inflammation.

Keywords: androgen; androgen receptor; asthma; lung; macrophage; monocyte; sex difference; sex hormone.

Figure 1

Sex differences in lung diseases discussed in this Review and how they may be connected to the effects of androgens (and estrogens) on inflammatory macrophages in the lung.

Figure 2

The effects of androgens on mouse and human monocytes and macrophages in vitro. The consequences of androgen exposure of monocytes and macrophages are shown. Green boxes indicate that the effect is to dampen proinflammatory responses or be considered immunosuppressive. The red boxes indicate a response that would increase inflammation. CCR2, C-C chemokine receptor type 2; DHT, dihydroxytestosterone; DHEA, dihydroepiandrosterone; PCa, prostate cancer; PGE2, prostaglandin E2; ROS, reactive oxygen species.