Androgens Upregulate Endometrial Epithelial Progesterone Receptor Expression: Potential Implications for Endometriosis

Babayev, Samir; Park, Chan Woo; Keller, Patrick W.; Carr, Bruce R.; Word, R. Ann; Bükülmez, Orhan

doi:10.1177/1933719117691145

Cited by 19 publications

(15 citation statements)

References 37 publications

(47 reference statements)

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“…DHT may inhibit PGR expression in cultured luteal cells through the AR pathway, as the inhibitory effect of DHT on PGR expression was blocked by flutamide. These findings in sheep luteal cells are not in accordance with findings in previous reports that demonstrated the ability of DHT to stimulate PGR expression in human endometrial epithelial (Babayev et al, 2017) and breast cancer cells (Liberato et al, 1993). It is difficult to compare these studies because different species and cells were used.…”

Section: Discussioncontrasting

confidence: 92%

Dihydrotestosterone synthesis in the sheep corpus luteum and its potential mechanism in luteal regression

Xiao

Song

et al. 2019

Journal Cellular Physiology

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Corpus luteum (CL) regression is a complex physiological process. Previous studies have shown that dihydrotestosterone (DHT) may be involved in regulating CL regression, but the mechanism is still unclear. In this study, we evaluated the localization of the two isoforms of DHT synthetase 5α‐reductase (5α‐red1 and 5α‐red2) and androgen receptor (AR) in sheep CL, and investigated 5α‐red1, 5α‐red2, AR, and DHT levels at different luteal stages of CL (early, middle, and late phase) by immunohistochemistry, quantitative real‐time polymerase chain reaction, and western blot analysis. Moreover, we cultured luteal cells from middle phase CL and treated them with different concentrations of DHT (10−10–10 −6 M) and the AR antagonist flutamide (10 −5 M), to evaluate whether DHT is involved in the regulation of progesterone (P4) secretion and progesterone nuclear receptor (PGR) expression and whether these effects are regulated by the AR pathway. We also investigated the effects of DHT and flutamide on prostaglandin F2α (PGF2α) secretion and apoptotic gene and protein expression. Our results showed that 5α‐red1, 5α‐red2, and AR were expressed in the CL, and their expression and DHT levels were changed during the luteal phase. DHT was involved in mediating P4 and PGF2α secretion and PGR and apoptotic gene and protein expression. The effects of DHT on CL were at least partially regulated by the AR pathway. This study reveals the mechanism of action of DHT on sheep CL regression and lays the foundation for further exploration of androgen regulation of CL function.

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Section: Discussioncontrasting

confidence: 92%

Dihydrotestosterone synthesis in the sheep corpus luteum and its potential mechanism in luteal regression

Xiao

Song

et al. 2019

Journal Cellular Physiology

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“…GSTM1, GSTP1, GSTT1 ) (22), hormone receptors (e.g. PR, AR ) (23), estrogen metabolism (e.g. ESR1 ) (24), growth factors (e.g.…”

Section: Introductionmentioning

confidence: 99%

Endometriosis Knowledgebase: a gene-based resource on endometriosis

Joseph

Mahale

2019

Database

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Endometriosis is a complex, benign, estrogen-dependent gynecological disorder with an incidence of ~10% women in reproductive age. The implantation and growth of endometrial cells outside the uterus leads to the development of endometriosis. Endometriosis is also associated with comorbid conditions like cardiovascular and autoimmune diseases. The absence of non-invasive diagnostic markers, delayed diagnosis, high risk of recurrence of the disease on surgical removal of the tissue and absence of a definitive cure for endometriosis makes it imperative to gain insights into the complex etiology of endometriosis. A plethora of genes identified from blood and endometrial biopsies, involved in different pathways like steroid metabolism, angiogenesis, inflammation, etc. have been associated with endometriosis. However, the exact mechanism and genetic etiology of endometriosis still remain unclear. The polygenic nature of the disease, incongruent phenotypic manifestations in different ethnic populations and information scattered in literature makes it difficult to delineate the sub-network of genes that will aid in disease diagnosis and effective treatment. Endometriosis Knowledgebase is a manually curated database with information on genes associated with endometriosis. It holds information on 831 genes, their associated polymorphisms, gene ontologys, pathways and diseases. Genes in the database are enriched in pathways important for cell signaling, immune regulation and reproduction. A genetic overlap is seen between endometriosis and cancers, endocrine/reproductive, nervous system, immune and metabolic diseases. Network analysis of genes in the Endometriosis Knowledgebase helped predict 13 new candidate genes for endometriosis. These genes were found to be enriched in biological processes associated with endometriosis. The Endometriosis Knowledgebase and incorporated tools for gene and sequence-based analysis will benefit both researchers and clinicians working in the realm of reproductive biology.

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“… 79 In addition to the proliferation and stimulation of endometrial cells and the increased expression of an own receptor, upon estradiol activation, the ER is translocated to the nucleus and binds to a PGR promoter, thereby increasing the expression of PR. 27 , 60 , 80 Therefore, the endometrium should be susceptible to estrogen, so that it eventually reacts to progesterone hormone action. Progesterone not only increases the synthesis of its own receptors, it also decreases ER and PR expression as part of its own biological activity.…”

Section: Resultsmentioning

confidence: 99%

Current Knowledge on Endometriosis Etiology: A Systematic Review of Literature

Михалева¹,

Radzinsky²,

Оразов³

et al. 2021

IJWH

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Objective To review the mechanisms of endometriosis development, including those related to epigenetic mutations, cellular dysregulation, inflammatory processes, and oxidative stress. Methods A systematic literature review regarding current aspects of endometriosis etiology, genesis and development was performed using the PubMed, Google Scholar, and eLibrary databases. Keywords included endometriosis, etiology, development, genesis, associations and mechanisms. A multilingual search was performed. Results Several mechanisms underline the pathophysiological pathways for endometriosis development. Epigenetic mutations, external and internal influences, and chronic conditions have a significant impact on endometriosis development, survival and regulation. Several historically valid theories on endometriosis development were discussed, as well as updated findings. Conclusion Despite recent advances, fundamental problems in understanding endometriosis remain unresolved. The identification of unknown circulating epithelial progenitors or stem cells that are responsible for epithelial growth in both the endometrium and endometriotic foci seems to be the next step in solving these questions.

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Androgens Upregulate Endometrial Epithelial Progesterone Receptor Expression: Potential Implications for Endometriosis

Abstract: Androgens may mediate endometrial effects through upregulation of PR gene and protein expression. Endometrial PR upregulation by androgens is mediated, at least in part, through AR.

Cited by 19 publications

References 37 publications

Dihydrotestosterone synthesis in the sheep corpus luteum and its potential mechanism in luteal regression

Dihydrotestosterone synthesis in the sheep corpus luteum and its potential mechanism in luteal regression

Endometriosis Knowledgebase: a gene-based resource on endometriosis

Current Knowledge on Endometriosis Etiology: A Systematic Review of Literature

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