scholarly journals Estrogen-Dependent and -Independent Estrogen Receptor-α Signaling Separately Regulate Male Fertility

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2898-2905 ◽  
Author(s):  
Kerstin W. Sinkevicius ◽  
Muriel Laine ◽  
Tamara L. Lotan ◽  
Karolina Woloszyn ◽  
John H. Richburg ◽  
...  

Estrogen receptor-α (ERα) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERα mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERα knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERα that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ERα pathways. Surprisingly, we found that ligand-independent ERα signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ERα signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ERα knock-in (ENERKI) mice with the ERα selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ERα in vivo, we discovered male fertility required neonatal estrogen-mediated ERα signaling. Thus, our work indicates both estrogen-dependent and -independent pathways play separable roles in male murine reproductive tract development and that the role of ERα in human infertility should be examined more closely.

2003 ◽  
Vol 17 (2) ◽  
pp. 203-208 ◽  
Author(s):  
Marie K. Lindberg ◽  
Sofia Movérare ◽  
Stanko Skrtic ◽  
Hui Gao ◽  
Karin Dahlman-Wright ◽  
...  

Abstract Estrogen is of importance for the regulation of adult bone metabolism. The aim of the present study was to determine the role of estrogen receptor-β (ERβ) in vivo on global estrogen-regulated transcriptional activity in bone. The effect of estrogen in bone of ovariectomized mice was determined using microarray analysis including 9400 genes. Most of the genes (95% = 240 genes) that were increased by estrogen in wild-type (WT) mice were also increased by estrogen in ERβ-inactivated mice. Interestingly, the average stimulatory effect of estrogen on the mRNA levels of these genes was 85% higher in ERβ-inactivated than in WT mice, demonstrating that ERβ reduces estrogen receptor-α (ERα)-regulated gene transcription in bone. The average stimulatory effect of estrogen on estrogen-regulated bone genes in ERα-inactivated mice was intermediate between that seen in WT and ERαβ double-inactivated mice. Thus, ERβ inhibits ERα-mediated gene transcription in the presence of ERα, whereas, in the absence of ERα, it can partially replace ERα. In conclusion, our in vivo data indicate that an important physiological role of ERβ is to modulate ERα-mediated gene transcription supporting a “Ying Yang” relationship between ERα and ERβ in mice.


Reproduction ◽  
2010 ◽  
Vol 140 (5) ◽  
pp. 767-776 ◽  
Author(s):  
Anna J Korzekwa ◽  
Mamadou M Bah ◽  
Andrzej Kurzynowski ◽  
Karolina Lukasik ◽  
Agnieszka Groblewska ◽  
...  

Recently, we showed that leukotrienes (LTs) regulate ovarian cell functionin vitro. The aim of this study was to examine the role of LTs in corpus luteum (CL) function during both the estrous cycle and early pregnancyin vivo. mRNA expression of LT receptors (BLTfor LTB4andCYSLTfor LTC4), and 5-lipoxygenase (5-LO) in CL tissue and their localization in the ovary were studied during the estrous cycle and early pregnancy. Moreover, concentrations of LTs (LTB4and C4) in the CL tissue and blood were measured.5-LOandBLTmRNA expression increased on days 16–18 of the cycle, whereasCYSLTmRNA expression increased on days 16–18 of the pregnancy. The level of LTB4was evaluated during pregnancy compared with the level of LTC4, which increased during CL regression. LT antagonists influenced the duration of the estrous cycle: the LTC4antagonist (azelastine) prolonged the luteal phase, whereas the LTB4antagonist (dapsone) caused earlier luteolysisin vivo. Dapsone decreased progesterone (P4) secretion and azelastine increased P4secretion during the estrous cycle. In summary, LT action in the bovine reproductive tract is dependent on LT type: LTB4is luteotropic during the estrous cycle and supports early pregnancy, whereas LTC4is luteolytic, regarded as undesirable in early pregnancy. LTs are produced/secreted in the CL tissue, influence prostaglandin function, and serve as important factors during the estrous cycle and early pregnancy in cattle.


Endocrinology ◽  
1998 ◽  
Vol 139 (6) ◽  
pp. 2982-2987 ◽  
Author(s):  
Cheryl S. Rosenfeld ◽  
Venkataseshu K. Ganjam ◽  
Julia A. Taylor ◽  
Xiaohui Yuan ◽  
James R. Stiehr ◽  
...  

1974 ◽  
Vol 139 (6) ◽  
pp. 1464-1472 ◽  
Author(s):  
David H. Katz ◽  
Toshiyuki Hamaoka ◽  
Baruj Benacerraf

The present studies were designed to probe the role(s) of T cells in preventing or altering tolerance induction in hapten-specific B cells. This was accomplished by using hapten conjugates of normally immunogenic heterologous carriers to selectively inhibit 2,4-dinitrophenyl (DNP)-primed B cells in adoptive transfer experiments in vivo. The data provide strong indications that one critical role of T-cell participation in humoral responses to antigens is to circumvent the development of a tolerogenic signal that, in the absence of such T-cell function, might otherwise ensue after binding of the antigenic determinants by specific precursor B lymphocytes.


2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
K. Svechnikov ◽  
G. Izzo ◽  
L. Landreh ◽  
J. Weisser ◽  
O. Söder

During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs) on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.


2018 ◽  
Vol 374 (2) ◽  
pp. 389-412 ◽  
Author(s):  
M. Kotula-Balak ◽  
P. Pawlicki ◽  
A. Milon ◽  
W. Tworzydlo ◽  
M. Sekula ◽  
...  

Author(s):  
Richard R Lee ◽  
Karen P Phillips

Canonical estrogen receptors (ER α/β) have a genomic mechanism of action, functioning as nuclear transcription factors for estrogen-dependent genes. Estrogen receptors are well established within the male reproductive tract with estrogen playing an essential role for male fertility. The recent characterization of novel G-protein coupled estrogen receptor GPR30 (alternatively known as GPER1), depending on non-genomic intracellular signaling pathways to transduce estrogenic signals, requires a re-examination of the roles of estrogen receptors in male reproduction. Further, the affinity of environmental estrogens (xenoestrogens) for estrogen receptor subtypes may provide additional understanding of the reproductive effects of these chemicals on male fertility. Here we review the structure and functions of each estrogen receptor within the context of male reproduction, with special consideration of the reproductive implications of xenoestrogen exposure. 


2020 ◽  
Vol 63 (6) ◽  
pp. 564-571
Author(s):  
Xiaodong Xie ◽  
Xiaofei Song ◽  
Xin Liu ◽  
Xiaogang Luo ◽  
Maidina Nabijiang ◽  
...  

<b><i>Purpose:</i></b> GATA4 has emerged as a novel regulator that plays a critical role in mediating senescence. However, the role of GATA4 in age-related cataract (ARC), the leading cause of visual impairment, requires further elucidation. <b><i>Methods:</i></b> GATA4 expression was measured by quantitative RT-PCR and capillary Western immunoassay (WES). The MTT assay, EdU assay, and rhodamine-123/Hoechst and calcein-AM/propidium iodide double staining were used to investigate the role of GATA4 in the viability, proliferation, and apoptosis of cultured human lens epithelial cells (HLECs). <b><i>Results:</i></b> HLECs were subjected to 3 different treatment models, including prolonged exposure to low-dose H<sub>2</sub>O<sub>2</sub>, UVB irradiation, and mild heating, to simulate senescence and apoptosis. GATA4 expression was significantly increased in these models in a time- and dose-dependent manner. Overexpression of GATA4 reduced cell viability, accelerated apoptosis development, and reduced the proliferation of HLECs. Furthermore, the expression of GATA4 from ARC was up-regulated at both mRNA and at protein level compared with clear lenses. <b><i>Conclusion:</i></b> GATA4 is up-regulated in all 3 models of HLECs in vitro and the cells from ARC lenses in vivo. Up-regulation of GATA4 mediates HLEC dysfunction. GATA4-mediated effects in HLECs would provide a novel insight into the pathogenesis of ARC.


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