The role of peripheral gonadotropin-releasing hormone receptors in female reproduction

Yu, Bo; Ruman, Jane; Christman, Gregory M.

doi:10.1016/j.fertnstert.2010.08.045

Cited by 54 publications

(37 citation statements)

References 88 publications

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“…GnRH receptors are expressed not only in the pituitary and in normal peripheral tissues [122] , but also in various tumor cells like melanoma, prostate and endometrial carcinomas, leiomyomas, leiomyosarcomas, breast cancer, choriocarcinoma, epithelial and stromal tumors of the ovary [122,123] . The activation of the peripheral GnRH receptor, which is coupled to the Gi protein in uterine leiomyosarcoma, ovarian and endometrial carcinomas, decreased intracellular cAMP levels leading to a down-regulation of gene transcription and antiproliferative effects in tumor cells [122] . Indeed, the repressive action of GnRH-I receptor on cell proliferation has been demonstrated in hormone-related tumors like prostate, breast, ovary and endometrium cancer [124] .…”

Section: Gpcrs Activated By Hormonesmentioning

confidence: 99%

“…Indeed, the repressive action of GnRH-I receptor on cell proliferation has been demonstrated in hormone-related tumors like prostate, breast, ovary and endometrium cancer [124] . GnRH and the cognate receptors were also involved in the stimulation of motility and invasion in ovarian cancer cells [125,126] , however several studies suggested a protective role elicited by GnRH analogues against gonadal damage during chemotherapy in diverse types of tumors [122] . On the basis of these findings, GnRH analogues are used in many endocrinedependent malignancies such as breast, endometrial, epithelial and stromal ovarian cancer.…”

Section: Gpcrs Activated By Hormonesmentioning

confidence: 99%

“…The antitumor activity of GnRH analogues was presumed to result from desensitization and/ or decrease of GnRH receptors in the pituitary, with the consequent decline in gonadotropin secretion and gonadal hormone production. Nevertheless, GnRH analogues were shown to suppress directly the growth of endometrial, ovarian, breast and prostate tumors and uterine leiomyoma [122,127,128] . Likewise, the growth of prostate cancer cells in vitro and in tumor xenografts was inhibited by activating the GnRH receptor or by GnRH receptor blockade [129] .…”

Section: Gpcrs Activated By Hormonesmentioning

confidence: 99%

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GPCRs and cancer

Lappano

2012

Acta Pharmacol Sin

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G-protein-coupled receptors (GPCRs), which represent the largest gene family in the human genome, play a crucial role in multiple physiological functions as well as in tumor growth and metastasis. For instance, various molecules like hormones, lipids, peptides and neurotransmitters exert their biological effects by binding to these seven-transmembrane receptors coupled to heterotrimeric G-proteins, which are highly specialized transducers able to modulate diverse signaling pathways. Furthermore, numerous responses mediated by GPCRs are not dependent on a single biochemical route, but result from the integration of an intricate network of transduction cascades involved in many physiological activities and tumor development. This review highlights the emerging information on the various responses mediated by a selected choice of GPCRs and the molecular mechanisms by which these receptors exert a primary action in cancer progression. These findings provide a broad overview on the biological activity elicited by GPCRs in tumor cells and contribute to the identification of novel pharmacological approaches for cancer patients.

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Section: Gpcrs Activated By Hormonesmentioning

confidence: 99%

Section: Gpcrs Activated By Hormonesmentioning

confidence: 99%

Section: Gpcrs Activated By Hormonesmentioning

confidence: 99%

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GPCRs and cancer

Lappano

2012

Acta Pharmacol Sin

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“…GnRHR expression has been detected in reproductive tissues including the ovary, testes, endometrium, myometrium, prostate, breast, and placenta [34]. Unique transcription initiation sites have been characterized in pituitary, ovarian, and placental tissues, which likely explain tissue-specific expression of this transcript.…”

Section: Discussionmentioning

confidence: 99%

Association of miR-938G>A Polymorphisms with Primary Ovarian Insufficiency (POI)-Related Gene Expression

Cho

Ahn

et al. 2017

IJMS

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MicroRNAs (miRNAs) post-transcriptionally regulate gene expression in animals and plants. The aim of this study was to investigate whether polymorphisms in miR-938 are associated with the risk of primary ovarian insufficiency (POI) and POI-related target gene regulation. We identified the miR-938G>A polymorphisms within the seed sequence of mature miRNA and aligned the seed sequence with the 3′ untranslated region (UTR) of the gonadotropin-releasing hormone receptor (GnRHR) mRNA, a miR-938 target gene. We found that the binding of miR-938 to the 3′-UTR of GnRHR mRNA was significantly different between normal and variant alleles. Our data suggests that the dysregulation of miR-938G>A influences the binding to GnRHR and that miR-938G>A polymorphisms might contribute to regulation of POI-related target genes.

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“…3 Although the primary function of GnRH is to regulate pituitary gonadotropin secretion, GnRH also appears to have autocrine and paracrine functions in diverse tissues (e.g., ovary, placenta). 4 The regulation of GnRH secretion is complex and involves overlapping pathways, which likely increases the robustness of central reproductive function. However, there are no known parallel or backup pathways for the stimulation of gonadotropin secretion.…”

Section: Gonadotropin-releasing Hormone: the Final Common Pathway Formentioning

confidence: 99%