Activation of G protein-coupled estrogen receptor 1 mimics, but does not mediate, the anti-proliferative action of estradiol on pituitary lactotrophs in primary culture

Mitsui, Tetsuo; Ishida, M.; Izawa, Masako; Ai, Jun

doi:10.1507/endocrj.ej16-0079

Cited by 4 publications

(3 citation statements)

References 49 publications

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“…One of the first studies about the non-genomic action of sex steroids demonstrated that immediately after the administration of 17-β estradiol (E2) to ovariectomized rat, the level of uterine cyclic adenosine monophosphate (cAMP) was doubled [5]. Several other studies showed that sex hormones exert a variety of prompt functional effects on different tissues, such as cancer cells in breast [6], pituitary glands [7], sperms [8], nerve cells [9] and many other targets.…”

Section: Introductionmentioning

confidence: 99%

Non-genomic actions of sex hormones on pregnant uterine contractility in rats: An in vitro study at term

et al. 2020

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The non-genomic (prompt) actions of sex steroids on pregnant uterine contractility are not fully explored yet, the aim of our study was to clarify such effects of 17-β estradiol (E2), progesterone (P4) and testosterone (T) on late (22-day) pregnant uterine contractions together with the signaling pathways in rats in vitro. Methods: The uterine effects of sex steroids on KCl-stimulated contractions were examined in the presence of genomic pathway blocker actinomycin D and cycloheximide, sex hormone receptor antagonists (flutamide, fulvestrant, mifepristone) and also after removing the endometrium. The modifications in uterine G-protein activation and cAMP levels were also detected. Results: T and E2 both relaxed the uterine contractions in the concentration range of 10 −8-10 −3 M with an increase in the activated G-protein and cAMP levels of the uterus, while P4 was ineffective. Cycloheximide, actinomycin D, antagonist for T and E2 were not able to modify the responses along with the endothelium removal. Mifepristone blocked the relaxing effects of T and E2 and reduced the activation of G-protein and the formation of cAMP. Significance: T and E2 can inhibit KCl-stimulated contractions in the late pregnant uterus in high concentrations and in a non-genomic manner. Their actions are mediated by a G-protein coupled receptor that can be blocked by mifepristone. A single and high dose of T or E2 might be considered in premature contractions, however, further preclinical and clinical studies are required for the approval of such a therapeutic intervention.

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Section: Introductionmentioning

confidence: 99%

Non-genomic actions of sex hormones on pregnant uterine contractility in rats: An in vitro study at term

et al. 2020

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“…GPER is expressed ubiquitously and has diverse biological effects, including vascular hypertrophy, regulation of cell growth, migration and apoptotic cell death [82]. However, the estradiol-mediated effect on proliferation of lactotropic cells in primary culture seems not to be due to GPER signaling [83]. The physiological roles of GPER in the pituitary are still not completely understood, but it seems to be involved in modulation of secretion of gonadotropins [84] and PRL [70] (Figure 3).…”

Section: Effects Of Estradiol On Differentiated Lactotropic Cells In mentioning

confidence: 99%

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

Šošić‐Jurjević

Ajdžanović

Miljić

et al. 2020

IJMS

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Estrogen signaling plays an important role in pituitary development and function. In sensitive rat or mice strains of both sexes, estrogen treatments promote lactotropic cell proliferation and induce the formation of pituitary adenomas (dominantly prolactin or growth-hormone-secreting ones). In male patients receiving estrogen, treatment does not necessarily result in pituitary hyperplasia, hyperprolactinemia or adenoma development. In this review, we comprehensively analyze the mechanisms of estrogen action upon their application in male animal models comparing it with available data in human subjects. Sex-specific molecular targets of estrogen action in lactotropic (PRL) cells are highlighted in the context of their proliferative and secretory activity. In addition, putative effects of estradiol on the cellular/tumor microenvironment and the contribution of postnatal pituitary progenitor/stem cells and transdifferentiation processes to prolactinoma development have been analyzed. Finally, estrogen-induced morphological and hormone-secreting changes in pituitary thyrotropic (TSH) and adrenocorticotropic (ACTH) cells are discussed, as well as the putative role of the thyroid and/or glucocorticoid hormones in prolactinoma development, based on the current scarce literature.

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“…The genomic effects of estrogen are relatively slow and take place in hours while some 'pregenomic' or rapid actions involving second messenger activation have also been described [13,23,24]. A membrane-bound G-protein coupled ER (GPER1) belonging to G-protein coupled receptor (GPCR) superfamily has recently been defined [13,25,26]. This receptor was shown to be rapidly activated upon estrogen binding and induce stimulation of adenylyl cyclase pathway [13,24].…”

Section: Introductionmentioning

confidence: 99%

G-protein Coupled Estrogen Receptor Expression in Growth Hormone Secreting and Non-Functioning Adenomas

Özkaya

Sayitoğlu

Çomunoğlu

et al. 2020

Exp Clin Endocrinol Diabetes

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Purpose To evaluate the expression of G-protein coupled estrogen receptor (GPER1), aromatase, estrogen receptor α (ERα), estrogen receptor β (ERβ), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) in GH-secreting and non-functioning adenomas (NFA). Methods Thirty patients with acromegaly and 27 patients with NFA were included. Gene expression was determined via quantitative reverse transcription polymerase chain reaction (QRT-PCR). Protein expression was determined via immunohistochemistry. Results There was no difference, in terms of gene expression of aromatase, ERα, PTTG, and FGF2 between the two groups (p>0.05 for all). ERβ gene expression was higher and GPER1 gene expression was lower in GH-secreting adenomas than NFAs (p<0.05 for all). Aromatase and ERβ protein expression was higher in GH-secreting adenomas than NFAs (p=0.01). None of the tumors expressed ERα. GPER1 expression was detected in 62.2% of the GH-secreting adenomas and 45% of NFAs. There was no difference in terms of GPER1, PTTG, FGF2 H scores between the two groups (p>0.05 for all). GPER1 gene expression was positively correlated to ERα, ERβ, PTTG, and FGF2 gene expression (p<0.05 for all). There was a positive correlation between aromatase and GPER1 protein expression (r=0.31; p=0.04). Conclusions GPER1 is expressed at both gene and protein level in a substantial portion of GH-secreting adenomas and NFAs. The finding of a positive correlation between GPER1 and ERα, ERβ, PTTG, and FGF2 gene expression and aromatase and GPER1 protein expression suggests GPER1 along with aromatase and classical ERs might mediate the effects of estrogen through upregulation of PTTG and FGF2.

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Activation of G protein-coupled estrogen receptor 1 mimics, but does not mediate, the anti-proliferative action of estradiol on pituitary lactotrophs in primary culture

Cited by 4 publications

References 49 publications

Non-genomic actions of sex hormones on pregnant uterine contractility in rats: An in vitro study at term

Non-genomic actions of sex hormones on pregnant uterine contractility in rats: An in vitro study at term

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

G-protein Coupled Estrogen Receptor Expression in Growth Hormone Secreting and Non-Functioning Adenomas

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