scholarly journals Differential Regulation of Estrogen Receptor α and β mRNAs in the Rat Uterus during Pregnancy and Labor: Possible Involvement of Estrogen Receptors in Oxytocin Receptor Regulation

2003 ◽  
Vol 50 (5) ◽  
pp. 579-587 ◽  
Author(s):  
Takuya MURATA ◽  
Kazumi NARITA ◽  
Kazumasa HONDA ◽  
Shigeru MATSUKAWA ◽  
Takashi HIGUCHI
2007 ◽  
Vol 67 (11) ◽  
pp. 5513-5521 ◽  
Author(s):  
Vanessa Duong ◽  
Nathalie Boulle ◽  
Sylvain Daujat ◽  
Jérôme Chauvet ◽  
Sandrine Bonnet ◽  
...  

Endocrinology ◽  
1999 ◽  
Vol 140 (12) ◽  
pp. 5712-5718 ◽  
Author(s):  
Wen Xuan Wu ◽  
Xiao Hong Ma ◽  
Toshiyuki Yoshizato ◽  
Norio Shinozuka ◽  
Peter W. Nathanielsz

Abstract In the present study, we characterized four myometrial contraction-associated proteins (mCAPs): oxytocin receptor (OTR), prostaglandin H synthase 2 (PGHS2), estrogen receptor α (ERα), and heat shock protein 90 (Hsp90) messenger RNA (mRNA) expression in the nongravid horn of pregnant sheep and compared them with their expression in the gravid horn that is exposed to a greater degree of stretch. We also examined the regulatory effects of estrogen and progesterone on OTR mRNA expression in ovariectomized nonpregnant sheep. In addition, we determined the ontogeny of mCAP expression in the gravid horn throughout late pregnancy and during spontaneous term labor. Gravid horn and nongravid horn myometria were removed under general anesthesia from control ewes not in labor at 130–140 days gestational age (dGA; n = 3) and during betamethasone-induced labor (n = 6) at the same gestational age. Gravid horn myometrium was also collected from ewes not in labor at 95 dGA (n = 3), 101–110 dGA (n = 3), 111–120 dGA (n = 3), 121–130 dGA (n = 3), 131–140 dGA (n = 3), and 141–145 dGA (n = 4) and from ewes in spontaneous term labor (n = 4). All ewes were carrying single fetuses. Myometrium was also collected from ovariectomized nonpregnant ewes treated with saline (n = 5), estradiol (50 μg/day; n = 5), progesterone (0.3 g, intravaginally; n = 5), and estradiol plus progesterone (n = 5). Myometrial RNA was extracted and analyzed by Northern blot for OTR, PGHS2, ERα, and Hsp90 mRNA, normalized for 18S ribosomal RNA orβ -actin. ERα, Hsp90, OTR, and PGHS2 mRNA were all significantly up-regulated during betamethasone-induced labor (P< 0.01) in gravid and nongravid horn myometrium. The level of gravid horn OTR mRNA during labor was 3 times the level of nongravid horn OTR mRNA (P < 0.0001). Gravid horn PGHS2 mRNA was also higher than nongravid horn PGHS2 (P < 0.02). In contrast, in spontaneous term labor nongravid horn, ERα and Hsp90 mRNA were similar to gravid horn. Myometrial ERα and Hsp90 mRNA remained unchanged throughout late pregnancy and increased at spontaneous term labor (P < 0.05). In contrast, myometrial OTR increased around 130 dGA (P < 0.01) and further increased at spontaneous term labor (P< 0.02). Progesterone significantly inhibited myometrial OTR mRNA expression in nonpregnant sheep and estradiol antagonized progesterone’s inhibitory effect. Mechanical stretch differentially regulated mCAP mRNA expression in the ovine gravid horn and nongravid horn. Mechanical stretch appears largely responsible for increased OTR mRNA and to a lesser degree PGHS2 mRNA. In addition, endocrine factors may be required for full activation of OTR and PGHS2 mRNA associated with labor. ERα and Hsp90 mRNA are not under the control of uterine stretch in keeping with our previous results, indicating that systemic hormones such as estradiol, are prime regulators for these two mCAP mRNA expression during labor.


2019 ◽  
Vol 20 (10) ◽  
pp. 2465 ◽  
Author(s):  
Marilena Marraudino ◽  
Alice Farinetti ◽  
Maria-Angeles Arevalo ◽  
Stefano Gotti ◽  
GianCarlo Panzica ◽  
...  

Developmental actions of estradiol in the hypothalamus are well characterized. This hormone generates sex differences in the development of hypothalamic neuronal circuits controlling neuroendocrine events, feeding, growth, reproduction and behavior. In vitro, estradiol promotes sexually dimorphic effects on hypothalamic neuritogenesis. Previous studies have shown that developmental actions of the phytoestrogen genistein result in permanent sexually dimorphic effects in some behaviors and neural circuits in vivo. In the present study, we have explored if genistein, like estradiol, affects neuritogenesis in primary hypothalamic neurons and investigated the estrogen receptors implicated in this action. Hypothalamic neuronal cultures, obtained from male or female embryonic day 14 (E14) CD1 mice, were treated with genistein (0.1 µM, 0.5 µM or 1 µM) or vehicle. Under basal conditions, female neurons had longer primary neurites, higher number of secondary neurites and higher neuritic arborization compared to male neurons. The treatment with genistein increased neuritic arborization and the number of primary neurites and decreased the number of secondary neurites in female neurons, but not in male neurons. In contrast, genistein resulted in a significant increase in primary neuritic length in male neurons, but not in female neurons. The use of selective estrogen receptor antagonists suggests that estrogen receptor α, estrogen receptor β and G-protein-coupled estrogen receptors are involved in the neuritogenic action of genistein. In summary, these findings indicate that genistein exerts sexually dimorphic actions on the development of hypothalamic neurons, altering the normal pattern of sex differences in neuritogenesis.


2005 ◽  
Vol 186 (1) ◽  
pp. 51-60 ◽  
Author(s):  
J Varayoud ◽  
J G Ramos ◽  
L Monje ◽  
V Bosquiazzo ◽  
M Muñoz-de-Toro ◽  
...  

The gene for estrogen receptor α (ERα) has been shown to be under complex hormonal control and its activity can be regulated by mRNA alternative splicing. Here we examined the regulation of ERα transcription and translation in the rat uterus by ovarian steroid hormones. We examined whether expression of ERα mRNA splice isoforms is hormonally regulated in ovariectomized (OVX) and cycling rats. Adult OVX female rats were treated daily with 17-β estradiol (E2) (0.05 μg/rat or 5 μg/rat), progesterone (P4) (1 mg/rat) or a combination of both hormones for 4 days. Animals were killed 24 h after the last injection and uterine horns were removed. In order to determine whether ERα mRNA isoforms are differentially expressed under various physiological conditions, animals were evaluated at proestrus, estrus and diestrus. The ERα protein and mRNA were detected by immunohistochemistry and comparative RT-PCR analysis respectively. The presence of ERα mRNA isoforms was evaluated using a nested RT-PCR assay. In OVX control rats, ERα mRNA and protein levels were high, demonstrating a constitutive expression of the ERα gene in the uterus. When animals received P4 or the high dose of E2, a significant decrease in both ERα mRNA and protein was observed in the uterus. However, when rats were protein was treated with the low dose of E2, only the ERα down-regulated; no changes were observed in ERα mRNA expression. In addition to the full-length ERα mRNA, OVX control rat uteri expressed three shorter transcripts: Σ3, Σ4 and Σ3,4 (lacking exon 3, exon 4, or both 3 and 4 respectively). Surprisingly, when OVX animals were treated with P4, the low dose of E2 or a combination of both steroids, expression of the Σ3 isoform was completely abolished. During the estrous cycle, all ERα mRNA splicing variants were detected at proestrus and estrus. However, in diestrus, significant low levels of the Σ3 isoform were observed. In summary, our results suggest a dose-dependent relationship between E2 concentrations and the level of control in the ERα transcription–translation cascade. Moreover, the alternative splicing of the ERα primary transcript is influenced by the hormonal milieu, suggesting that these events could affect the estrogen responsiveness of the rat uterus during the estrous cycle.


2014 ◽  
Vol 306 (8) ◽  
pp. E937-E944 ◽  
Author(s):  
Alesha B. Castillo ◽  
Jason W. Triplett ◽  
Fredrick M. Pavalko ◽  
Charles H. Turner

Mechanical loading is an important regulator in skeletal growth, maintenance, and aging. Estrogen receptors have a regulatory role in mechanically induced bone adaptation. Estrogen receptor-α (ERα) is known to enhance load-induced bone formation, whereas ERβ negatively regulates this process. We hypothesized that ERβ regulates mechanical signaling in osteoblasts. We tested this hypothesis by subjecting primary calvarial cells isolated from wild-type and ERβ-knockout mice (BERKO) to oscillatory fluid flow in the absence or presence of estradiol (E2). We found that the known responses to fluid shear stress, i.e., phosphorylation of the mitogen-activated protein kinase ERK and upregulation of COX-2 expression, were inhibited in BERKO cells in the absence of E2. Flow-induced increase in prostaglandin E2 (PGE2) release was not altered in BERKO cells in the absence of E2, but was increased when E2 was present. Additionally, immunofluorescence analysis and estrogen response element luciferase assays revealed increased ERα expression and flow- and ligand-induced nuclear translocation as well as transcriptional activity in BERKO cells in both the presence and absence of E2. Taken together, these data suggest that ERβ plays both ligand-dependent and ligand-independent roles in mechanical signaling in osteoblasts. Furthermore, our data suggest that one mechanism by which ERβ regulates mechanotransduction in osteoblasts may result from its inhibitory effect on ERα expression and function. Targeting estrogen receptors (e.g., inhibiting ERβ) may represent an effective approach for prevention and treatment of age-related bone loss.


2021 ◽  
Vol 12 ◽  
Author(s):  
Takuro Goto ◽  
Hiroshi Miyamoto

Epidemiological data have indicated that there are some sex-related differences in bladder cancer. Indeed, the incidence of bladder cancer in men has been substantially higher than that in women throughout the world, while women tend to have higher stage disease and poorer prognosis. These gender disparities have prompted to investigate sex hormones and their cognitive receptors in bladder cancer. Specifically, estrogen receptors, including estrogen receptor-α and estrogen receptor-β, have been shown to contribute to urothelial carcinogenesis and cancer progression, as well as to modulating chemosensitivity in bladder cancer, although conflicting findings exist. Meanwhile, immunohistochemical studies in surgical specimens have assessed the expression of estrogen receptors and related proteins as well as its associations with clinicopathologic features of bladder cancer and patient outcomes. This review article summarizes and discusses available data indicating that estrogen receptor signaling plays an important role in urothelial cancer.


2017 ◽  
Vol 6 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Anastasia K Armeni ◽  
Konstantinos Assimakopoulos ◽  
Dimitra Marioli ◽  
Vassiliki Koika ◽  
Euthychia Michaelidou ◽  
...  

Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA) gene polymorphism (rs2234693-PvuII) (T→C substitution) and oxytocin receptor gene polymorphism (rs53576) (G→A substitution) with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days), were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs), polycystic ovary syndrome (PCOS), thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype) of rs2234693 (PvuII) polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic) of rs53576 (OXTR) polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII) and A allele of rs53576 (OXTR) polymorphisms (T + A group) was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.


Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4272-4275 ◽  
Author(s):  
Andrew L. Siebel ◽  
Helen M. Gehring ◽  
Irna Grace T. Reytomas ◽  
Laura J. Parry

This study used relaxin (RLX) gene knockout mice (Rlx−/−) to investigate the effects of RLX on myometrial oxytocin receptor (OTR) and estrogen receptor (ER)-α gene expression in late gestation. We also characterized the temporal expression of the RLX receptor (LGR7) and demonstrated gene transcripts in the myometrium of Rlx+/+ and Rlx−/− mice. There was a significant (P < 0.05) decrease in myometrial LGR7 gene expression on d 17.5 and 18.5 post coitum (pc) compared with earlier stages of gestation, but no differences between Rlx+/+ and Rlx−/− mice. Myometrial OTR mRNA levels increased at the end of gestation in Rlx+/+ but not Rlx−/− mice. ERα gene expression was up-regulated on d 14.5 pc in Rlx+/+ mice, with mRNA levels remaining high throughout late gestation. In contrast, ERα mRNA levels were significantly lower in Rlx−/− mice on d 14.5 and 18.5 pc. These data show that the increases in myometrial OTR and ERα expression in late pregnant Rlx+/+ mice were attenuated in Rlx−/− mice. The effects of RLX on OTRs are probably mediated via activation of ERα. Finally, RLX receptor expression in the myometrium of Rlx−/− mice did not differ from wild-type mice, implying that RLX does not influence expression of its receptor.


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