Identification of Three Putative GnRH Receptor Subtypes in Vertebrates

Troskie, Brigitte E.; Illing, Nicola; Rumbak, Elaine; Sun, Yu; Hapgood, Janet P.; Sealfon, Stuart C.; Conklin, Darrell; Millar, Robert P.

doi:10.1006/gcen.1998.7156

Cited by 98 publications

(67 citation statements)

References 11 publications

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“…One pair was designed to amplify EC3 which is the domain shown to determine ligand specificity (Flanagan et al 1994). With this pair we succeeded in obtaining the sequence of EC3 from fish, amphibian, reptile and bird species (Troskie et al 1998). All of these species had a sequence homologous to the cloned mammalian GnRH receptors.…”

Section: Search For Gnrh Receptor Homologsmentioning

confidence: 99%

“…However, in the amphibian and reptilian DNA distinctly different second putative GnRH receptors (designated Type II) with the EC3 sequences PEMLTEEKVPPVLSHI and PEMLTR GQVPPSLSHI respectively, were found. The tblastn program (Altschul et al 1990) was used to query the Merck-WashU EST database for homology to the reptile EC3 sequence and EST200 816 was identified (Troskie et al 1998). The same approach was employed using the complete sequence of the human Type I GnRH receptor.…”

Section: Search For Gnrh Receptor Homologsmentioning

confidence: 99%

“…One EST (EST200 816) was identified as having acceptable homology to the putative Type II reptile EC3 (Troskie et al 1998) and also to the region of TM6 to the end of TM7 of the Type I GnRH receptor. Another EST (EST157 566) was found with homology to the EC2 and TM5 regions.…”

Section: Est Homologsmentioning

confidence: 99%

“…To date only one form of GnRH receptor (designated here as Type I) has been cloned from mammals (Eidne et al 1992, Kaiser et al 1992, Kakar et al 1992, Reinhart et al 1992, Tsutsumi et al 1992, Brooks et al 1993, Chi et al 1993, Illing et al 1993, Kakar et al 1993, Perrin et al 1993, Troskie et al 1998. We therefore designed a series of pairs of degenerate oligonucleotides to the mammalian GnRH receptor and cloned short sequences encoding the extracellular (EC) loop 3 domain (EC3) which suggested the presence of three different GnRH receptor genes in species of fish, amphibian, reptile and bird (Troskie et al 1998). Two of these are most like the mammalian GnRH pituitary receptors (Type I) and were therefore designated Type Ia and Type Ib (Troskie et al 1998).…”

Section: Introductionmentioning

confidence: 99%

“…We therefore designed a series of pairs of degenerate oligonucleotides to the mammalian GnRH receptor and cloned short sequences encoding the extracellular (EC) loop 3 domain (EC3) which suggested the presence of three different GnRH receptor genes in species of fish, amphibian, reptile and bird (Troskie et al 1998). Two of these are most like the mammalian GnRH pituitary receptors (Type I) and were therefore designated Type Ia and Type Ib (Troskie et al 1998). The third was more different and was designated Type II.…”

Section: Introductionmentioning

confidence: 99%

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A novel human GnRH receptor homolog gene: abundant and wide tissue distribution of the antisense transcript

Millar

Conklin²,

Lofton–Day³

et al. 1999

Journal of Endocrinology

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Gonadotropin releasing hormone (GnRH) regulates the reproductive system through a specific G-protein-coupled receptor (GPCR) in pituitary gonadotropes. The existence of two (or more) forms of GnRH in most vertebrates suggested the existence of GnRH receptor subtypes (I and II). Using sequence information for extracellular loop 3 of a putative Type II GnRH receptor from a reptile species, we have looked for a Type II GnRH receptor gene in the human genome EST (expressed sequence tag) database. A homolog was identified which has 45% and 41% amino acid identity with exons 2 and 3 of the known human GnRH pituitary receptor (designated Type I) and much lower homology with all other GPCRs. A total of 27 contiguous ESTs was found and comprised a continuous sequence of 1642 nucleotides. The EST sequences were confirmed in the cloned human gene and in PCR products of cDNA from several tissues. All EST transcripts detected were in the antisense orientation with respect to the novel GnRH receptor sequence and were highly expressed in a wide range of human brain and peripheral tissues. PCR of cDNA from a wide range of tissues revealed that intronic sequence equivalent to intron 2 of the Type I GnRH receptor was retained. The failure to splice out putative intron sequences in transcripts which spanned exon-intron boundaries is expected in antisense transcripts, as candidate donor and acceptor sites were only present in the gene when transcribed in the orientation encoding the GnRH receptor homolog. No transcripts extended 5 to the sequence corresponding to intron 2 of the Type I GnRH as the antisense transcripts terminated in poly A due to the presence of a polyadenylation signal sequence in the putative intron 2 when transcribed in the antisense orientation. These findings suggest that a Type II GnRH receptor gene has arisen during vertebrate evolution and is also present in the human. However, the receptor may have become vestigial in the human, possibly due to the abundant and universal tissue transcription of the opposite DNA strand to produce antisense RNA.

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Section: Search For Gnrh Receptor Homologsmentioning

confidence: 99%

Section: Search For Gnrh Receptor Homologsmentioning

confidence: 99%

Section: Est Homologsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A novel human GnRH receptor homolog gene: abundant and wide tissue distribution of the antisense transcript

Millar

Conklin²,

Lofton–Day³

et al. 1999

Journal of Endocrinology

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Immunohistochemical localization of three different prepro‐GnRHs in the brain and pituitary of the European sea bass (Dicentrarchus labrax) using antibodies to the corresponding GnRH‐associated peptides

González-Martı́nez

Zmora

Mañanós

et al. 2002

J of Comparative Neurology

142

120

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The distribution of the cells expressing three prepro-gonadotrophin-releasing hormones (GnRH), corresponding to salmon GnRH (sGnRH), seabream GnRH (sbGnRH), and chicken GnRH-II (cGnRH-II) forms, was studied in the brain and pituitary of the sea bass (Dicentrarchus labrax) by using immunohistochemistry. To circumvent the cross-reactivity problems of antibodies raised to GnRH decapeptides, we used specific antibodies generated against the different sea bass GnRH-associated peptides (GAP): salmon GAP (sGAP), seabream GAP (sbGAP), and chicken-II GAP (cIIGAP). The salmon GAP immunostaining was mostly detected in terminal nerve neurons but also in ventral telencephalic and preoptic perikarya. Salmon GAP-immunoreactive (ir) fibers were observed mainly in the forebrain, although sGAP-ir projections were also evident in the optic tectum, mesencephalic tegmentum, and ventral rhombencephalon. The pituitary only receives a few sGAP-ir fibers. The seabream GAP-ir cells were mainly detected in the preoptic area. Nevertheless, sbGAP-ir neurons were also found in olfactory bulbs, ventral telencephalon, and ventrolateral hypothalamus. The sbGAP-ir fibers were only observed in the ventral forebrain, innervating strongly the pituitary gland. Finally, chicken-II GAP immunoreactivity was only detected in large synencephalic cells, which are the origin of a profuse innervation reaching the telencephalon, preoptic area, hypothalamus, thalamus, pretectum, posterior tuberculum, mesencephalic tectum and tegmentum, cerebellum, and rhombencephalon. However, no cIIGAP-ir fibers were detected in the hypophysis. These results corroborate the overlapping of sGAP- and sbGAP-expressing cells in the forebrain of the sea bass, and provide, for the first time, unambiguous information on the distribution of projections of the three different GnRH forms expressed in the brain of a single species.

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Localization of the three GnRH types and GnRH receptors in the brain of a cichlid fish: Insights into their neuroendocrine and neuromodulator functions

Soga¹,

Ogawa²,

Millar³

et al. 2005

J of Comparative Neurology

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The cognate receptor for any of the known gonadotropin-releasing hormones (GnRHs) has not been directly demonstrated. In order to establish this and shed light on the functions of GnRH types, we analyzed the neuroanatomical location and time of initial expression of three distinct GnRH receptors (GnRH-Rs) and the three endogenous GnRHs in the brain of developing and sexually mature tilapia Oreochromis niloticus using immunocytochemistry. In all age groups, including males and females, GnRH-RIA was seen specifically in gonadotropes (Parhar et al. [2002] J Neuroendocrinol 14:657-665) but was undetectable in the brain. On day 8 after fertilization, GnRH-RIB was first seen in the periventricular hypothalamus (lateral recess nucleus, posterior recess nucleus, posterior tuberal nucleus) and GnRH-RIII in the olfactory epithelium, olfactory bulb, telencephalon, preoptic region, mediobasal hypothalamus, thalamus, mesencephalon, and in the hindbrain. Double-label immunocytochemistry showed GnRH1 (Ser(8) GnRH)-immunoreactive neuronal processes projecting mainly to the proximal pars distalis of the pituitary, while GnRH2 (His(5), Trp(7), Tyr(8) GnRH) and GnRH3 (Trp(7), Leu(8) GnRH) fibers were observed in close association with cells containing GnRH-RIB and GnRH-RIII in the brain. These results suggest that GnRH-RIA might be hypophysiotropic in nature, whereas GnRH-RIB and GnRH-RIII could have additional neuromodulatory functions. Further, evidence of close proximity of GnRH-R-containing cells and neuronal processes of multiple GnRH types suggests complex cross-talk between several GnRH ligands and GnRH-Rs.

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Identification of Three Putative GnRH Receptor Subtypes in Vertebrates

Cited by 98 publications

References 11 publications

A novel human GnRH receptor homolog gene: abundant and wide tissue distribution of the antisense transcript

A novel human GnRH receptor homolog gene: abundant and wide tissue distribution of the antisense transcript

Immunohistochemical localization of three different prepro‐GnRHs in the brain and pituitary of the European sea bass (Dicentrarchus labrax) using antibodies to the corresponding GnRH‐associated peptides

Localization of the three GnRH types and GnRH receptors in the brain of a cichlid fish: Insights into their neuroendocrine and neuromodulator functions

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