Estrogens in Male Physiology

Abstract

Estrogens have historically been associated with female reproduction, but work over the last two decades established that estrogens and their main nuclear receptors (ESR1 and ESR2) and G protein-coupled estrogen receptor (GPER) also regulate male reproductive and nonreproductive organs. 17β-Estradiol (E2) is measureable in blood of men and males of other species, but in rete testis fluids, E2 reaches concentrations normally found only in females and in some species nanomolar concentrations of estrone sulfate are found in semen. Aromatase, which converts androgens to estrogens, is expressed in Leydig cells, seminiferous epithelium, and other male organs. Early studies showed E2 binding in numerous male tissues, and ESR1 and ESR2 each show unique distributions and actions in males. Exogenous estrogen treatment produced male reproductive pathologies in laboratory animals and men, especially during development, and studies with transgenic mice with compromised estrogen signaling demonstrated an E2 role in normal male physiology. Efferent ductules and epididymal functions are dependent on estrogen signaling through ESR1, whose loss impaired ion transport and water reabsorption, resulting in abnormal sperm. Loss of ESR1 or aromatase also produces effects on nonreproductive targets such as brain, adipose, skeletal muscle, bone, cardiovascular, and immune tissues. Expression of GPER is extensive in male tracts, suggesting a possible role for E2 signaling through this receptor in male reproduction. Recent evidence also indicates that membrane ESR1 has critical roles in male reproduction. Thus estrogens are important physiological regulators in males, and future studies may reveal additional roles for estrogen signaling in various target tissues.

Steroidal hormone and morphological responses in the prostate anterior lobe in different cancer grades after Celecoxib and Goniothalamin treatments in TRAMP mice

“…Another important factor for the structural and functional maintenance and overall prostate homeostasis are the androgenic and estrogenic hormones (Prins et al, 1991;Weihua et al, 2001;Cooke et al, 2017). It is known that estrogens act synergistically to testosterone, influencing prostate function under normal and pathological conditions, and so could lead to the development of glandular lesions (Cunha et al, 2001;Weihua et al, 2001).…”

Integrated mRNA and miRNA expression profile analyses reveal the potential roles of sex‐biased miRNA–mRNA pairs in gonad tissues of the Chinese concave‐eared torrent frog (Odorrana tormota)

“…SYCP3 is required for normal meiosis during spermatogenesis and male fertility (Miyamoto et al, ), and was verified as a potential target of DAZL‐mediated translation in the male germline (Reynolds, Collier, Bingham, Gray, & Cooke, ). Furthermore, in vertebrates, while estrogens play a major role in female reproduction, they are also involved in the development and control of male reproductive functions (Cooke, Nanjappa, Ko, Prins, & Hess, ). The role of estrogen receptors (including ESR1 and ESR2) in male gonads is to ensure germ cell development, Sertoli and Leydig cell functionality and spermatogenesis progression (Verderame & Scudiero, ).…”

Immunolocalization of G Protein‐Coupled Estrogen Receptor in the Pig Epididymis

“…Therefore, the expression of GPER1 is extensive in male tracts, suggesting a possible role for E2 signaling through this receptor in male reproduction. (Cooke et al, ). However, GPER's overall role in E2 signaling in males remains unclear (Madak‐Erdogan et al, ; Levin ; Gaudet et al, ).…”