Journal of Endocrinology and Reproduction

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Membrane Estrogen Receptor 1 is Required for Normal Reproduction in Male and Female Mice


Affiliations
1 Department of Physiological Sciences, University of Florida, Gainesville, FL 32610, United States
2 Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States
     

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Steroid hormones, acting through their cognate nuclear receptors, are critical for many reproductive and non-reproductive functions. Over the past two decades, it has become increasingly clear that in addition to cytoplasmic/nuclear steroid receptors that alter gene transcription when liganded, a small fraction of cellular steroid receptors are localized to the cell membranes, where they mediate rapid steroid hormone effects. 17β-Estradiol (E2), a key steroid hormone for both male and female reproduction, acts predominately through its main receptor, estrogen receptor 1 (ESR1). Most ESR1 is nuclear; however, 5-10 % of ESR1 is localized to the cell membrane after being palmitoylated at cysteine 451 in mice. This review discusses reproductive phenotypes of a newly-developed mouse model with a C451A point mutation that precludes membrane targeting of ESR1. This transgenic mouse, termed the nuclear-only ESR1 (NOER) mouse, shows extensive male and female reproductive abnormalities and infertility despite normally functional nuclear ESR1 (nESR1). These results provide the first in vivo evidence that membrane-initiated E2/ESR1 signaling is required for normal male and female reproductive functions and fertility. Signaling mechanisms for membrane ESR1 (mESR1), as well as how mESR1 works with nESR1 to mediate estrogen effects, are still being established. We discuss some possible mechanisms by which mESR1 might facilitate nESR1 signaling, as well as the emerging evidence that mESR1 might be a major mediator of epigenetic effects of estrogens, which are potentially linked to various adult-onset pathologies.

Keywords

Efferent Ductules, 17β-Estradiol, Spermatogenesis, Testis, Uterus.
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  • Membrane Estrogen Receptor 1 is Required for Normal Reproduction in Male and Female Mice

Abstract Views: 338  |  PDF Views: 1

Authors

Manjunatha K. Nanjappa
Department of Physiological Sciences, University of Florida, Gainesville, FL 32610, United States
Ana M. Mesa
Department of Physiological Sciences, University of Florida, Gainesville, FL 32610, United States
Sergei G. Tevosian
Department of Physiological Sciences, University of Florida, Gainesville, FL 32610, United States
Laura de Armas
Department of Physiological Sciences, University of Florida, Gainesville, FL 32610, United States
Rex A. Hess
Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States
Indrani C. Bagchi
Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States
Paul S. Cooke
Department of Physiological Sciences, University of Florida, Gainesville, FL 32610, United States

Abstract


Steroid hormones, acting through their cognate nuclear receptors, are critical for many reproductive and non-reproductive functions. Over the past two decades, it has become increasingly clear that in addition to cytoplasmic/nuclear steroid receptors that alter gene transcription when liganded, a small fraction of cellular steroid receptors are localized to the cell membranes, where they mediate rapid steroid hormone effects. 17β-Estradiol (E2), a key steroid hormone for both male and female reproduction, acts predominately through its main receptor, estrogen receptor 1 (ESR1). Most ESR1 is nuclear; however, 5-10 % of ESR1 is localized to the cell membrane after being palmitoylated at cysteine 451 in mice. This review discusses reproductive phenotypes of a newly-developed mouse model with a C451A point mutation that precludes membrane targeting of ESR1. This transgenic mouse, termed the nuclear-only ESR1 (NOER) mouse, shows extensive male and female reproductive abnormalities and infertility despite normally functional nuclear ESR1 (nESR1). These results provide the first in vivo evidence that membrane-initiated E2/ESR1 signaling is required for normal male and female reproductive functions and fertility. Signaling mechanisms for membrane ESR1 (mESR1), as well as how mESR1 works with nESR1 to mediate estrogen effects, are still being established. We discuss some possible mechanisms by which mESR1 might facilitate nESR1 signaling, as well as the emerging evidence that mESR1 might be a major mediator of epigenetic effects of estrogens, which are potentially linked to various adult-onset pathologies.

Keywords


Efferent Ductules, 17β-Estradiol, Spermatogenesis, Testis, Uterus.

References





DOI: https://doi.org/10.18311/jer%2F2017%2F21013