scholarly journals Membrane-Localized Estrogen Receptor 1 Is Required for Normal Male Reproductive Development and Function in Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2909-2919 ◽  
Author(s):  
Manjunatha K. Nanjappa ◽  
Rex A. Hess ◽  
Theresa I. Medrano ◽  
Seth H. Locker ◽  
Ellis R. Levin ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Seminiferous Tubules ◽  
Normal Male ◽  
Epididymal Sperm ◽  
Histological Changes ◽  
17Β Estradiol ◽  
And Function ◽  
Estrogen Receptor 1 ◽  
Daily Sperm Production ◽  
Efferent Ductule

Estrogen receptor 1 (ESR1) mediates major reproductive functions of 17β-estradiol (E2). Male Esr1 knockout (Esr1KO) mice are infertile due to efferent ductule and epididymal abnormalities. The majority of ESR1 is nuclear/cytoplasmic; however, a small fraction is palmitoylated at cysteine 451 in mice and localized to cell membranes, in which it mediates rapid E2 actions. This study used an Esr1 knock-in mouse containing an altered palmitoylation site (C451A) in ESR1 that prevented cell membrane localization, although nuclear ESR1 was expressed. These nuclear-only estrogen receptor 1 (NOER) mice were used to determine the roles of membrane ESR1 in males. Epididymal sperm motility was reduced 85% in 8-month-old NOER mice compared with wild-type controls. The NOER mice had decreased epididymal sperm viability and greater than 95% of sperm had abnormalities, including coiled midpieces and tails, absent heads, and folded tails; this was comparable to 4-month Esr1KO males. At 8 months, daily sperm production in NOER males was reduced 62% compared with controls. The NOER mice had histological changes in the rete testes, efferent ductules, and seminiferous tubules that were comparable with those previously observed in Esr1KO males. Serum T was increased in NOER males, but FSH, LH, and E2 were unchanged. Critically, NOER males were initially subfertile, becoming infertile with advancing age. These findings identify a previously unknown role for membrane ESR1 in the development of normal sperm and providing an adequate environment for spermatogenesis.

scholarly journals Mice lacking membrane estrogen receptor 1 are protected from reproductive pathologies resulting from developmental estrogen exposure†

2019 ◽  
Vol 101 (2) ◽  
pp. 392-404 ◽  
Author(s):  
Manjunatha K Nanjappa ◽  
Theresa I Medrano ◽  
Ana M Mesa ◽  
Madison T Ortega ◽  
Paul D Caldo ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Wild Type ◽  
Epithelial Proliferation ◽  
Ductus Deferens ◽  
Male And Female ◽  
Estrogen Exposure ◽  
Synthetic Estrogen ◽  
High Incidence ◽  
17Β Estradiol ◽  
Estrogen Receptor 1

Abstract Both membrane and nuclear fractions of estrogen receptor 1 (ESR1) mediate 17β-estradiol (E2) actions. Mice expressing nuclear (n)ESR1 but lacking membrane (m)ESR1 (nuclear-only estrogen receptor 1 [NOER] mice) show reduced E2 responsivity and reproductive abnormalities culminating in adult male and female infertility. Using this model, we investigated whether reproductive pathologies caused by the synthetic estrogen diethylstilbestrol (DES) are mitigated by mESR1 ablation. Homozygous and heterozygous wild-type (WT and HET, respectively) and NOER male and female mice were subcutaneously injected with DES (1 mg/kg body weight [BW]) or vehicle daily from postnatal day (PND) 1–5. Uterine histology was assessed in select DES-treated females at PND 5, whereas others were ovariectomized at PND 60 and treated with E2 (10 μg/kg BW) or vehicle 2 weeks later. Neonatal DES exposure resulted in ovary-independent epithelial proliferation in the vagina and uterus of WT but not NOER females. Neonatal DES treatment also induced ovary-independent adult expression of classical E2-induced transcripts (e.g., lactoferrin [Ltf] and enhancer of zeste homolog 2 [Ezh2]) in WT but not NOER mice. At PND 90, DES-treated WT and HET males showed smaller testes and a high incidence of bacterial pyogranulomatous inflammation encompassing the testes, epididymis and occasionally the ductus deferens with spread to lumbar lymph nodes; such changes were largely absent in NOER males. Results indicate that male and female NOER mice are protected from deleterious effects of neonatal DES, and thus mESR1 signaling is required for adult manifestation of DES-induced reproductive pathologies in both sexes.

17β-Estradiol induces nongenomic effects in renal intercalated cells through G protein-coupled estrogen receptor 1

2012 ◽  
Vol 302 (3) ◽  
pp. F358-F368 ◽  
Author(s):  
Marlene Vind Hofmeister ◽  
Helle Hasager Damkier ◽  
Birgitte Mønster Christensen ◽  
Björn Olde ◽  
L. M. Fredrik Leeb-Lundberg ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Atpase Activity ◽  
Steroid Hormones ◽  
G Protein ◽  
Intercalated Cells ◽  
Ici 182,780 ◽  
Intracellular Ca ◽  
17Β Estradiol ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Steroid hormones such as 17β-estradiol (E2) are known to modulate ion transporter expression in the kidney through classic intracellular receptors. Steroid hormones are also known to cause rapid nongenomic responses in a variety of nonrenal tissues. However, little is known about renal short-term effects of steroid hormones. Here, we studied the acute actions of E2 on intracellular Ca2+ signaling in isolated distal convoluted tubules (DCT2), connecting tubules (CNT), and initial cortical collecting ducts (iCCD) by fluo 4 fluorometry. Physiological concentrations of E2 induced transient increases in intracellular Ca2+ concentration ([Ca2+]i) in a subpopulation of cells. The [Ca2+]i increases required extracellular Ca2+ and were inhibited by Gd3+. Strikingly, the classic E2 receptor antagonist ICI 182,780 also increased [Ca2+]i, which is inconsistent with the activation of classic E2 receptors. G protein-coupled estrogen receptor 1 (GPER1 or GPR30) was detected in microdissected DCT2/CNT/iCCD by RT-PCR. Stimulation with the specific GPER1 agonist G-1 induced similar [Ca2+]i increases as E2, and in tubules from GPER1 knockout mice, E2, G-1, and ICI 182,780 failed to induce [Ca2+]i elevations. The intercalated cells showed both E2-induced concanamycin-sensitive H+-ATPase activity by BCECF fluorometry and the E2-mediated [Ca2+]i increment. We propose that E2 via GPER1 evokes [Ca2+]i transients and increases H+-ATPase activity in intercalated cells in mouse DCT2/CNT/iCCD.

scholarly journals Contribution of G protein-coupled estrogen receptor 1 (GPER) to 17β-estradiol-induced developmental toxicity in zebrafish

2017 ◽  
Vol 186 ◽  
pp. 180-187 ◽  
Author(s):  
Graciel Diamante ◽  
Norma Menjivar-Cervantes ◽  
Man Sin Leung ◽  
David C. Volz ◽  
Daniel Schlenk
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Developmental Toxicity ◽  
17Β Estradiol ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

scholarly journals Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes of pituitary-specific Esr1 knockout female mice

Reproduction ◽  
2012 ◽  
Vol 143 (4) ◽  
pp. 549-558 ◽  
Author(s):  
José E Sánchez-Criado ◽  
Kourtney Trudgen ◽  
Yolanda Millán ◽  
Alfonso Blanco ◽  
José Monterde ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Pituitary Cells ◽  
Immunohistochemical Expression ◽  
Female Mice ◽  
Serum Lh ◽  
Pituitary Glands ◽  
17Β Estradiol ◽  
Lh Secretion ◽  
Estrogen Receptor 1

Estrogen receptor 1 and 2 (ESR1 and 2) mediate estrogen (E) action on gonadotrope function. While much is known about the effects of ESR1 on the gonadotrope, there is still some controversy regarding the effects of ESR2. To investigate the role of ESR2 in the gonadotrope, 45-day-old female mice of two different genotypes were used: wild type (WT) and pituitary (gonadotropes and thyrotropes)-specific Esr1 knockout (KO). All mice were ovariectomized (OVX) and 15 days later injected over 3 days with 2.5 μg 17β-estradiol (E2), 0.2 mg of the selective ESR1 or 2 agonists, propylpyrazole triol and diarylpropionitrile, respectively, or 0.1 ml oil. The day after treatment, anterior pituitary glands were dissected out for evaluation of gonadotrope ultrastructural morphology and pituitary immunohistochemical expression of progesterone receptor (Pgr (Pr)). Blood was collected and serum LH levels were assessed. Activation of ESR1 in WT mice resulted in the following: i) uterine ballooning and vaginal cornification, ii) negative feedback on LH secretion, iii) increased number of homogeneous (functional) gonadotropes, and iv) pituitary Pgr expression (35.9±2.0% of pituitary cells). Activation of ESR1 in KO mice induced normal uterine, vaginal, and LH secretion responses, but failed to increase the number of functional gonadotropes, and induced significantly lower Pgr expression (21.0±3.0% of pituitary cells) than in WT mice. Whilst activation of ESR2 had no significant effects in WT mice, it doubled the number of functional gonadotropes exhibited by KO mice injected with oil. It is concluded that E2 exerted its action in KO mouse gonadotropes via ESR2.

Regulation of AKT signaling in mouse uterus

Endocrinology ◽  
2021 ◽  
Author(s):  
Vijay K Sirohi ◽  
Theresa I Medrano ◽  
Ana M Mesa ◽  
Athilakshmi Kannan ◽  
Indrani C Bagchi ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Akt Signaling ◽  
Conditional Knockout ◽  
Model Systems ◽  
Epithelial Proliferation ◽  
Mouse Uterus ◽  
Akt Activation ◽  
Adult Mice ◽  
17Β Estradiol ◽  
Estrogen Receptor 1

Abstract 17β-Estradiol (E2) treatment of ovariectomized adult mice stimulates the uterine PI3K-AKT signaling pathway and epithelial proliferation through estrogen receptor 1 (ESR1). However, epithelial proliferation occurs independently of E2/ESR1 signaling in neonatal uteri. Similarly, estrogen-independent uterine epithelial proliferation is seen in adulthood in mice lacking Ezh2, critical for histone methylation, and in WT mice treated neonatally with estrogen. The role of AKT in this estrogen-independent uterine epithelial proliferation was the focus of this study. Expression of p-AKT and epithelial proliferation were high in estrogen receptor 1 knockout and WT mice at postnatal day 6 (PND 6), when E2 concentrations were low, indicating that neither ESR1 nor E2 are essential for p-AKT expression and epithelial proliferation in these mice. However, p-AKT levels and proliferation remained estrogen responsive in pre-weaning WT mice. Expression of p-AKT and proliferation were both high in uterine luminal epithelium of mice estrogenized neonatally and ovariectomized during adulthood. Increased expression of phosphorylated (inactive) EZH2 was also observed. Consistent with this, Ezh2 conditional knockout mice show ovary-independent uterine epithelial proliferation and high epithelial p-AKT. Thus, adult p-AKT expression is constitutive and E2/ESR1 independent in both model systems. Finally, E2-induced p-AKT expression and normal uterine proliferation did not occur in mice lacking membrane (m)ESR1, indicating a key role for mESR1 in AKT activation. These findings emphasize the importance of p-AKT activation in promoting uterine epithelial proliferation even when that proliferation is not E2/ESR1 dependent and further indicate that p-AKT can be uncoupled from E2/ESR1 signaling in several experimental scenarios.

Estrogen receptor β localization in the lizard (Podarcis s. sicula) testis

Zygote ◽  
2004 ◽  
Vol 12 (1) ◽  
pp. 39-42 ◽  
Author(s):  
Paolo Chieffi ◽  
Bruno Varriale
Keyword(s):  
Estrogen Receptor ◽  
Western Blot ◽  
Germ Cells ◽  
Male Fertility ◽  
Specific Weight ◽  
Estrogen Receptor Β ◽  
Normal Male ◽  
Immunocytochemical Analysis ◽  
Vertebrate Model ◽  
17Β Estradiol

There is increasing evidence that 17β-estradiol is necessary for normal male fertility. The aim of the present study was to characterize estrogen receptor β (ERβ) expression in a non-mammalian vertebrate model, the lizard (Podarcis s. sicula) testis. Immunocytochemical analysis shows that ERβ proteins are present among germ cells in the nucleus of the spermatogonia, in primary spermatocytes and spermatids. Western blot analysis with antibodies against the ERβ gene product revealed an isoform with a specific weight of 55 kDa. In conclusion, the widespread expression of ERβ in the Podarcis s. sicula testis is consistent with a role for estrogens in modulating spermatogenesis in the male.

scholarly journals 17β-Estradiol Confers Protection after Traumatic Brain Injury in the Rat and Involves Activation of G Protein-Coupled Estrogen Receptor 1

2013 ◽  
Vol 30 (17) ◽  
pp. 1531-1541 ◽  
Author(s):  
Nicole L. Day ◽  
Candace L. Floyd ◽  
Tracy L. D'Alessandro ◽  
William J. Hubbard ◽  
Irshad H. Chaudry
Keyword(s):  
Traumatic Brain Injury ◽  
Estrogen Receptor ◽  
Brain Injury ◽  
G Protein ◽  
17Β Estradiol ◽  
G Protein Coupled ◽  
Estrogen Receptor 1
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