The biology of gonadotropin hormone-releasing hormone: role in the control of tumor growth and progression in humans

@article{Limonta2003TheBO,
  title={The biology of gonadotropin hormone-releasing hormone: role in the control of tumor growth and progression in humans},
  author={Patrizia Limonta and Roberta Manuela Moretti and Marina Montagnani Marelli and Marcella Motta},
  journal={Frontiers in Neuroendocrinology},
  year={2003},
  volume={24},
  pages={279-295}
}
Role of gonadotropin-releasing hormone II in the mammalian nervous system
TLDR
Although it is unlikely to be a primary regulator of gonadotropin release, GnRH II appears to have a wide array of physiological and behavioral functions, and increasing evidence suggests that the behavioral effects of Gn RH II are mediated by receptor subtypes distinct from the type-1 GnRH receptor.
Gonadotropin‐releasing hormone and ovarian cancer: a functional and mechanistic overview
TLDR
The current understanding of the antiproliferative actions of Gn RH analogs, as well as the recent observations of GnRH effects on ovarian cancer cell apoptosis and motogenesis are summarized.
Antiproliferative Effects of GnRH Agonists: Prospects and Problems for Cancer Therapy
TLDR
Data on the effects of GnRH agonists on cell proliferation and apoptosis is reviewed, and hypotheses for investigation are put forward to determine whether the GnRH receptor acts as a tumor suppressor in neuroendocrine or epithelial cells.
Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals
TLDR
Uniquely, both GnRH2 and GnRHR2 are ubiquitously expressed; transcript levels are abundant in peripheral tissues and scarcely found in regions of the brain associated with gonadotropin secretion, suggesting a divergent role from GnRH1/GnRHR1.
REPRODUCTIVE FUNCTION AND ANTITUMOR ACTIVITY: DIFFERENT ROLES FOR THE HYPOTHALAMIC HORMONE GnRH
TLDR
In conclusion, GnRH-R are expressed not only at the pituitary level but also in a wide range of tumor tissues; these receptors are at present under investigation as an effective molecular target for the development of novel therapeutic strategies.
The mammalian type II gonadotropin-releasing hormone receptor : cloning, distribution and role in gonadotropin gene expression
TLDR
It is demonstrated for the first time that GnRH-1 may affect gonadotropin subunit gene expression via GnR HR-II in addition to GnRHR-I, and that Gn RH-2 also has the ability to regulate gonadotropic subunit genes expression via both receptors.
Regulation of Expression of Mammalian Gonadotrophin‐Releasing Hormone Receptor Genes
TLDR
The GnRHR is emerging as a potential target gene for facilitating cross‐talk between neuroendocrine, immune and stress‐response systems in multiple tissues via autocrine, paracrine and endocrine signalling.
Emerging Functions Of Gonadotropin‐Releasing Hormone II in Mammalian Physiology and Behaviour
  • A. Kauffman
  • Biology, Medicine
    Journal of neuroendocrinology
  • 2004
TLDR
It is likely that this evolutionarily conserved peptide has been co‐opted over evolutionary time to possess multiple regulatory functions in a broad range of biological aspects, including, but not limited to, reproduction.
Dissection of GnRH receptor-G protein coupling
TLDR
It is shown that the GnRH Iinduced inhibition of cell growth is dependent on Gq/11, src and extracellular signal regulated kinase (ERK) but is independent of the activity of protein kinase C (PKC), Ca, jun-N-terminal Kinase (JNK) or P38.
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References

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TLDR
Molecular phylogenetic analysis shows that this second GnRH-II gene is likely the result of a duplication before the appearance of vertebrates, and predicts the existence of a third GnRH form in humans and other vertebrates.
A gonadotropin-releasing hormone (GnRH) receptor specific for GnRH II in primates.
TLDR
It is demonstrated that a second receptor (type II) gene is present in the human genome, and the cloning and characterization of its cDNA from monkeys are reported, the first report of a GnRH type II receptor in mammals.
Evolutionary aspects of gonadotropin-releasing hormone and its receptor
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Evidence suggests that in most species the early-evolved and highly conserved chicken GnRH II has a neurotransmitter function, while the second form, which varies across classes, has a physiologic role in regulating gonadotropin release.
Origin of mammalian gonadotropin-releasing hormones.
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Studying of GnRH peptides and their genes have altered views on the origin, function, and regulation of this neuropeptide, and novel functions, in addition to the release of gonadotropins exist.
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TLDR
This work proposes three different GnRH lineages expressed by distinct brain areas in vertebrates, including the conserved cGnRH-II or mesencephalic lineage; or the hypothalamic or “releasing” lineage whose primary structure has diverged by point mutations.
Role of Gonadotropin-Releasing Hormone as an Autocrine Growth Factor in Human Ovarian Surface Epithelium1.
TLDR
Novel evidence is provided that GnRH may have antiproliferative effects in human ovarian surface epithelial cells and GnRH and its receptor have sequences identical to those found in the hypothalamus and pituitary, respectively.
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TLDR
GnRH-II may have biological effects similar to those of GnRH-I but is under differential hormonal regulation in the human ovary, suggesting that it may exert their antigonadotropic effect by down-regulating gonadotropin receptors.
GnRH II and type II GnRH receptors
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    Trends in Endocrinology & Metabolism
  • 2003
Biology of the gonadotropin-releasing hormone system in gynecological cancers.
TLDR
GnRH receptor interacts with the mitogenic signal transduction of growth factor receptors and related oncogene products associated with tyrosine kinase activity, via activation of a phosphotyrosine phosphatase, resulting in downregulation of cancer cell proliferation.
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