A Transcriptionally Active Human Type II Gonadotropin-Releasing Hormone Receptor Gene Homolog Overlaps Two Genes in the Antisense Orientation on Chromosome 1q.12

Morgan, Kevin; Conklin, Darrell; Pawson, Adam J.; Sellar, Robin; Ott, Thomas; Millar, Robert P.

doi:10.1210/en.2002-220622

Cited by 110 publications

(99 citation statements)

References 73 publications

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“…It may be that one acts as a hormone secreted into the blood circulation and one as a neuropeptide, in analogy with that found in brain, but this has to be further studied. Different receptors for GnRH 1 and 2 have been described in mammals although GnRH-R2 is not expressed as a fully functional receptor, due to a genomic stop sequence/frame shift [22,23]. However, both GnRH1 and GnRH2 are able to signal through the type 1 receptor [19].…”

Section: Discussionmentioning

confidence: 99%

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Sand

Bergvall

Ekblad

et al. 2013

Regulatory Peptides

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Section: Discussionmentioning

confidence: 99%

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Sand

Bergvall

Ekblad

et al. 2013

Regulatory Peptides

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“…Until now, attempts to clone and sequence of a full-length human GnRH-II receptor have not been successful (13). Morgan et al (14) found that the human GnRH-II receptor is expressed as a variety of splice variants and a functional human GnRH-II receptor transcript was not found. The GnRH-II receptor-like mRNA detected in this and in our previous study (6) is suspected to be non-functional because of the stop codon in the sequence.…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor

Gründker

Schlotawa

Viereck

et al. 2004

European Journal of Endocrinology

101

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Background: The majority of human endometrial and ovarian cancer cell lines express receptors for GnRH. Their proliferation is time-and dose-dependently reduced by GnRH-I and its superagonistic analogues. Recently, we have demonstrated that, in human endometrial and ovarian cancer cell lines except for the ovarian cancer cell line EFO-27, the GnRH-I antagonist cetrorelix has antiproliferative effects comparable to those of GnRH-I agonists, indicating that the dichotomy between GnRH-I agonists and antagonists might not apply to the GnRH system in cancer cells. We were also able to show that the proliferation of human endometrial and ovarian cancer cells was doseand time-dependently reduced by GnRH-II to a greater extent than by GnRH-I agonists. Objective: In this study we have assessed whether or not the antiproliferative effects of the GnRH-I antagonist cetrorelix in endometrial and ovarian cancer cells are mediated through the GnRH-I receptor. Methods: We analysed the antiproliferative effects of the GnRH-I agonist triptorelin, the GnRH-I antagonist cetrorelix and GnRH-II in a panel of endometrial and ovarian cancer cell lines expressing GnRH-I receptors, in the SK-OV-3 ovarian cancer cell line that does not express GnRH-I receptors, and in four GnRH-I receptor positive GnRH-I receptor knockout cell lines. Results: We found that, after knockout of the GnRH-I receptor, the antiproliferative effects of the GnRH-I agonist triptorelin were abrogated, whereas those of the GnRH-I antagonist cetrorelix and of GnRH-II persisted. Conclusions: These data suggest that, in endometrial and ovarian cancer cells, the antiproliferative effects of cetrorelix and of GnRH-II are not mediated through the GnRH-I receptor.

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“…Furthermore, analysis of DNA sequence data and functional studies indicate that there has been sporadic silencing or deletion of GnRH II and/ or the type II receptor in various mammals. Thus, GnRH I and GnRH II and the type I and type II GnRH receptors are expressed in some primates such as the marmoset [94] and green monkey while the type II GnRH receptor has been silenced in man and the chimpanzee by stop codons and frame shifts [101]. From a molecular genetics point of view, it is possible that, during evolution, the mammalian type II GnRH receptor gene came under functional pressure by close apposition of 5′ and 3′ anking genes (potentially leading to interference with transcription) and subsequent mutations led to gene silencing.…”

Section: Silencing Of Gnrhs and Gnrh Receptors In Mammalsmentioning

confidence: 99%

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

Millar

Pawson

Morgan

et al. 2008

Frontiers in Neuroendocrinology

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122

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Geoffrey Wingfield Harris' demonstration of hypothalamic hormones regulating pituitary function led to their structural identification and therapeutic utilization in a wide spectrum of diseases. Amongst these, Gonadotropin Releasing Hormone (GnRH) and its analogs are widely employed in modulating gonadotropin and sex steroid secretion to treat infertility, precocious puberty and many hormone-dependent diseases including endometriosis, uterine fibroids and prostatic cancer. While these effects are all mediated via modulation of the pituitary gonadotrope GnRH receptor and the G q signaling pathway, it has become increasingly apparent that GnRH regulates many extrapituitary cells in the nervous system and periphery. This review focuses on two such examples, namely GnRH analog effects on reproductive behaviors and GnRH analog effects on the inhibition of cancer cell growth. For both effects the relative activities of a range of GnRH analogs is distinctly different from their effects on the pituitary gonadotrope and different signaling pathways are utilized. As there is only a single functional GnRH receptor type in man we have proposed that the GnRH receptor can assume different conformations which have different selectivity for GnRH analogs and intracellular signaling proteins complexes. This ligand-induced selective-signaling recruits certain pathways while by-passing others and has implications in developing more selective GnRH analogs for highly specific therapeutic intervention.

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A Transcriptionally Active Human Type II Gonadotropin-Releasing Hormone Receptor Gene Homolog Overlaps Two Genes in the Antisense Orientation on Chromosome 1q.12

Cited by 110 publications

References 73 publications

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

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