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Second gene for gonadotropin-releasing hormone in humans.

ABSTRACT: Gonadotropin-releasing hormone (GnRH) is a decapeptide widely known for its role in regulating reproduction by serving as a signal from the hypothalamus to pituitary gonadotropes. In addition to hypothalamic GnRH (GnRH-I), a second GnRH form (pGln-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly; GnRH-II) with unknown function has been localized to the midbrain of many vertebrates. We show here that a gene encoding GnRH-II is expressed in humans and is located on chromosome 20p13, distinct from the GnRH-I gene that is on 8p21-p11.2. The GnRH-II genomic and mRNA structures parallel those of GnRH-I. However, in contrast to GnRH-I, GnRH-II is expressed at significantly higher levels outside the brain (up to 30x), particularly in the kidney, bone marrow, and prostate. The widespread expression of GnRH-II suggests it may have multiple functions. Molecular phylogenetic analysis shows that this second 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.

SUBMITTER: White RB

PROVIDER: S-EPMC18209 | biostudies-literature | 1998 Jan

REPOSITORIES: biostudies-literature

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Second gene for gonadotropin-releasing hormone in humans.

White R B RB Eisen J A JA Kasten T L TL Fernald R D RD

Proceedings of the National Academy of Sciences of the United States of America 19980101 1

Gonadotropin-releasing hormone (GnRH) is a decapeptide widely known for its role in regulating reproduction by serving as a signal from the hypothalamus to pituitary gonadotropes. In addition to hypothalamic GnRH (GnRH-I), a second GnRH form (pGln-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly; GnRH-II) with unknown function has been localized to the midbrain of many vertebrates. We show here that a gene encoding GnRH-II is expressed in humans and is located on chromosome 20p13, distinct from the GnRH-I ge ...[more]

PMID: 9419371

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Project description:BackgroundThe main objective of the present work was to compare the effects of the gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant) on the gene expression profiles of oocytes obtained from Iranian infertile couples undergoing in vitro fertilization (IVF).MethodsFifty infertile couples who underwent IVF between June 2012 and November 2013 at the Infertility Center of Tehran Women General Hospital, Tehran University of Medical Sciences, were included in this study. We included women that had undergone IVF treatment because of male factor, tubal factor, or unexplained infertility. The women randomly underwent controlled ovarian stimulation (COS) with either the GnRH-a (n = 26) or the GnRH-ant (n = 24). We obtained 50 germinal vesicle (GV) oocytes donated by women in each group. After the sampling, pool of 50 GV oocytes for each group was separately analyzed by quantitative polymerase chain reaction (qPCR).ResultThe expression levels of Adenosine triphosphatase 6 (ATPase 6), Bone morphogenetic protein 15 (BMP15), and Neuronal apoptosis inhibitory protein (NAIP) genes were significantly upregulated in the GnRH-ant group compared to the GnRH-a group, with the fold change of 3.990 (SD ± 1.325), 6.274 (SD ± 1.542), and 2.156 (SD ± 1.443), respectively, (P < 0.001). Growth differentiation factor 9 (GDF9) mRNA did not have any expression in the GnRH-a group; however, GDF9 mRNA was expressed in the GnRH-ant group. Finally, it was found that the genes involved in the DNA repairing and cell cycle checkpoint did not have any expression in either group.ConclusionThe present study showed, for the first time, the expression levels of genes involved in the cytoplasmic maturity (BMP15, GDF9), adenosine triphosphate production (ATPase 6), and antiapoptotic process (NAIP), in human GV oocytes were significantly higher in the GnRH-anta group than in the GnRH-a group in COS. Higher expression level of these genes when GnRH-ant protocol is applied, this protocol seems to be a more appropriate choice for women with poly cystic ovarian syndrome, because it can probably improve the expression of the aforementioned genes.Trial registrationCurrent Controlled Trials: IRCT 2014031112307 N3.

Project description:In vertebrates, the gonadotropin-releasing hormone (GnRH) decapeptide is secreted from hypothalamic nerve terminals to regulate reproduction via control of synthesis and release of pituitary gonadotropins. Only one GnRH peptide has been found in mammals, with one exception, although numerous other vertebrate species express more than one of the eight known decapeptide forms as shown by immunocytochemical labeling of distinct cell groups in the brain. However, neither the functional nor the evolutionary relationships among these GnRH forms are clear, because only one preprohormone gene sequence from any species has been reported. The most ubiquitous alternative form of GnRH is [His5,Trp7,Tyr8]GnRH (also referred to as chicken-II), which differs from the mammalian sequence at amino acids 5, 7, and 8. This peptide has been shown to have the most potent releasing-hormone activity, although immunocytochemical staining has suggested it is synthesized only in the mesencephalon. Here we report the cloning and expression pattern of the gene for the precursor of this form from the teleost fish Haplochromis burtoni. This is the second GnRH-encoding gene to be characterized in this species. The newly discovered preprohormone gene differs from that previously reported in two ways. First, whereas the original gene predicts only a single associated peptide, this one predicts two associated peptides, both of which appear to be unique. Second, the gene for [His5,Trp7,Tyr8]GnRH is expressed in only one cell group in the mesencephalon. In contrast, the previously reported gene is expressed only in the terminal nerve. The striking differences between the preprohormone structure and localization suggest that the genes coding for the two known GnRH forms in H. burtoni did not arise from a recent duplication event. Interestingly, neither of the two genes found to date in this species is expressed in cells which project from the hypothalamus to the pituitary, suggesting that yet a third gene coding for GnRH may exist.

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Second gene for gonadotropin-releasing hormone in humans.

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Second gene for gonadotropin-releasing hormone in humans.

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