Induction of G protein-coupled estrogen receptor (GPER) and nuclear steroid hormone receptors by gonadotropins in human granulosa cells

Pavlik, R.; Wypior, Gabriela; Hecht, Stefanie; Papadopoulos, Panos; Kupka, M.; Thaler, Christian J.; Wiest, I.; Pestka, Aurelia; Friese, Klaus; Jeschke, Udo

doi:10.1007/s00418-011-0846-7

Cited by 35 publications

(22 citation statements)

References 49 publications

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“…Luteinizing hormone was recently shown to regulate GPER expression at the mRNA and protein level in human granulosa cells (Pavlik et al, 2011). Interactions and cross-talk between GPER and growth factor receptors, particularly EGFR and IGFR, have been recently summarized by Maggiolini and colleagues (Bartella et al, 2012; Lappano et al, 2013).…”

Section: Interactions Of Gper With Other Receptorsmentioning

confidence: 99%

Estrogen biology: New insights into GPER function and clinical opportunities

Prossnitz

Barton

2014

Molecular and Cellular Endocrinology

323

267

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Estrogens play an important role in the regulation of normal physiology, aging and many disease states. Although the nuclear estrogen receptors have classically been described to function as ligand-activated transcription factors mediating genomic effects in hormonally regulated tissues, more recent studies reveal that estrogens also mediate rapid signaling events traditionally associated with G protein-coupled receptors. The G protein-coupled estrogen receptor GPER (formerly GPR30) has now become recognized as a major mediator of estrogen’s rapid cellular effects throughout the body. With the discovery of selective synthetic ligands for GPER, both agonists and antagonists, as well as the use of GPER knockout mice, significant advances have been made in our understanding of GPER function at the cellular, tissue and organismal levels. In many instances, the protective/beneficial effects of estrogen are mimicked by selective GPER agonism and are absent or reduced in GPER knockout mice, suggesting an essential or at least parallel role for GPER in the actions of estrogen. In this review, we will discuss recent advances and our current understanding of the role of GPER and certain drugs such as SERMs and SERDs in physiology and disease. We will also highlight novel opportunities for clinical development towards GPER-targeted therapeutics, for molecular imaging, as well as for theranostic approaches and personalized medicine.

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Section: Interactions Of Gper With Other Receptorsmentioning

confidence: 99%

Estrogen biology: New insights into GPER function and clinical opportunities

Prossnitz

Barton

2014

Molecular and Cellular Endocrinology

323

267

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“…It supports the unexpected results related to peritubular cells. The specificity of the antiserum was further substantiated by results of Western blotting experiments using human granulosa cells, recently reported to express GPER (Pavlik et al ., 2011; results not shown). To our knowledge GPER expression by the smooth-muscle-like peritubular cells of the testis has not been reported in previous studies using different antibodies and immunohistochemistry.…”

Section: Discussionmentioning

confidence: 86%

Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility

Sandner

Welter

Schwarzer³

et al. 2014

Andrology

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Besides the two nuclear estrogen receptors (ESR1/ESR2), the G protein-coupled estrogen receptor (GPER) was described in the human testis but little is known about testicular GPER during development or male infertility. We performed an immunohistochemical analysis using human and rhesus monkey testicular samples. The results obtained in adult primate testes showed GPER in interstitial and vascular cells as well as in the smooth muscle-like peritubular cells, which build the wall of seminiferous tubules. Expression of GPER was also found in cultured human testicular peritubular cells (HPTCs) by Western blotting and RT-PCR/sequencing. Furthermore, as seen in time-lapse videos of cultured cells, addition of a specific GPER agonist (G1) significantly reduced the numbers of HTPCs within 24 h. A GPER antagonist (G15) prevented this action, implying a role for GPER related to the control of cell proliferation or cell death of peritubular cells. Peritubular cell functions and their phenotype change, for example, during postnatal development and in cases of male infertility. The study of non-human primate samples revealed that GPER in peritubular cells was detectable only from the time of puberty onwards, while in samples from infantile and prepubertal monkeys only interstitial cells showed immunopositive staining. In testicular biopsies of men with mixed atrophy a reduction or loss of immunoreactive GPER was found in peritubular cells surrounding those tubules, in which spermatogenesis was impaired. In other cases of impaired spermatogenesis, namely when the tubular wall was fibrotically remodeled, a complete loss of GPER was seen. Thus, the observed inverse relation between the state of fertility and GPER expression by peritubular cells implies that the regulation of primate testicular peritubular cells by estrogens is mediated by GPER in both, health and disease.

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“…Recently a non-classical G protein-coupled estrogen receptor (GPER) was described (Revankar et al 2005;Thomas et al 2005b), indicating that estradiol can act rapidly independent of transcription. With no data available regarding the expression of GPER in human granulosa tissue and cells, Pavlik et al (2011) addressed this issue and could identify in their study GPER in human granulosa cells (GC). The authors additionally demonstrated that high concentrations of LH increased GPER protein expression.…”

Section: Reproductive System (Female)mentioning

confidence: 99%