Abstract
Introduction: The proposed evolutionary origins and corresponding nomenclature of bilaterian gonadotropin-releasing hormone (GnRH)-related neuropeptides have changed tremendously with the aid of receptor deorphanization. However, the reclassification of the GnRH and corazonin (CRZ) signaling systems in Lophotrochozoa remains unclear. Methods: We characterized GnRH and CRZ receptors in the mollusk Pacific abalone, Haliotis discus hannai (Hdh), by phylogenetic and gene expression analyses, bioluminescence-based reporter, Western blotting, substitution of peptide amino acids, in vivo neuropeptide injection, and RNA interference assays. Results: Two Hdh CRZ-like receptors (Hdh-CRZR-A and Hdh-CRZR-B) and three Hdh GnRH-like receptors (Hdh-GnRHR1-A, Hdh-GnRHR1-B, and Hdh-GnRHR2) were identified. In phylogenetic analysis, Hdh-CRZR-A and -B grouped within the CRZ-type receptors, whereas Hdh-GnRHR1-A/-B and Hdh-GnRHR2 clustered within the GnRH/adipokinetic hormone (AKH)/CRZ-related peptide-type receptors. Hdh-CRZR-A/-B and Hdh-GnRHR1-A were activated by Hdh-CRZ (pQNYHFSNGWHA-NH2) and Hdh-GnRH (pQISFSPNWGT-NH2), respectively. Hdh-CRZR-A/-B dually coupled with the Gαq and Gαs signaling pathways, whereas Hdh-GnRHR1-A was linked only with Gαq signaling. Analysis of substituted peptides, [I2S3]Hdh-CRZ and [N2Y3H4]Hdh-GnRH, and in silico docking models revealed that the N-terminal amino acids of the peptides are critical for the selectivity of Hdh-CRZR and Hdh-GnRHR. Two precursor transcripts for Hdh-CRZ and Hdh-GnRH peptides and their receptors were mainly expressed in the neural ganglia, and their levels increased in starved abalones. Injection of Hdh-CRZ peptide into abalones decreased food consumption, whereas Hdh-CRZR knockdown increased food consumption. Moreover, Hdh-CRZ induced germinal vesicle breakdown in mature oocytes. Conclusion: Characterization of Hdh-CRZRs and Hdh-GnRHRs and their cognate peptides provides new insight into the evolutionary route of GnRH-related signaling systems in bilaterians.
References
1.
Okubo K, Nagahama Y. Structural and functional evolution of gonadotropin-releasing hormone in vertebrates. Acta Physiol. 2008;193(1):3–15.
2.
Kah O, Lethimonier C, Somoza G, Guilgur LG, Vaillant C, Lareyre JJ. GnRH and GnRH receptors in metazoa: a historical, comparative, and evolutive perspective. Gen Comp Endocrinol. 2007;153(1–3):346–64.
3.
Amoss M, Burgus R, Blackwell R, Vale W, Fellows R, Guillemin R. Purification, amino acid composition and N-terminus of the hypothalamic Luteinizing hormone Releasing Factor (LRF) of ovine origin. Biochem Biophys Res Commun. 1971;44(1):205–10.
4.
Schally AV, Arimura A, Baba Y, Nair RM, Matsuo H, Redding TW, et al. Isolation and properties of the FSH and LH-releasing hormone. Biochem Biophys Res Commun. 1971;43(2):393–9.
5.
Seeburg PH, Adelman JP. Characterization of cDNA for precursor of human luteinizing hormone releasing hormone. Nature. 1984;311(5987):666–8.
6.
Reinhart J, Mertz LM, Catt KJ. Molecular cloning and expression of cDNA encoding the murine gonadotropin-releasing hormone receptor. J Biol Chem. 1992;267(30):21281–4.
7.
Tsutsumi M, Zhou W, Millar RP, Mellon PL, Roberts JL, Flanagan CA, et al. Cloning and functional expression of a mouse gonadotropin-releasing hormone receptor. Mol Endocrinol. 1992;6(7):1163–9.
8.
Roch GJ, Busby ER, Sherwood NM. GnRH receptors and peptides: skating backward. Gen Comp Endocrinol. 2014;209:118–34.
9.
Temple JL, Millar RP, Rissman EF. An evolutionarily conserved form of gonadotropin-releasing hormone coordinates energy and reproductive behavior. Endocrinology. 2003;144(1):13–9.
10.
Kauffman AS, Rissman EF. A critical role for the evolutionarily conserved gonadotropin-releasing hormone II: mediation of energy status and female sexual behavior. Endocrinology. 2004;145(8):3639–46.
11.
Matsuda K, Nakamura K, Shimakura S, Miura T, Kageyama H, Uchiyama M, et al. Inhibitory effect of chicken gonadotropin-releasing hormone II on food intake in the goldfish, Carassius auratus. Horm Behav. 2008;54(1):83–9.
12.
Schneider JS, Rissman EF. Gonadotropin-releasing hormone II: a multi-purpose neuropeptide. Integr Comp Biol. 2008;48(5):588–95.
13.
Umatani C, Oka Y. Multiple functions of non-hypophysiotropic gonadotropin releasing hormone neurons in vertebrates. Zoological Lett. 2019;5:23.
14.
Marvel M, Levavi-Sivan B, Wong TT, Zmora N, Zohar Y. Gnrh2 maintains reproduction in fasting zebrafish through dynamic neuronal projection changes and regulation of gonadotropin synthesis, oogenesis, and reproductive behaviors. Sci Rep. 2021;11(1):6657.
15.
Marvel MM, Spicer OS, Wong TT, Zmora N, Zohar Y. Knockout of Gnrh2 in zebrafish (Danio rerio) reveals its roles in regulating feeding behavior and oocyte quality. Gen Comp Endocrinol. 2019;280:15–23.
16.
Lindemans M, Janssen T, Beets I, Temmerman L, Meelkop E, Schoofs L. Gonadotropin-releasing hormone and adipokinetic hormone signaling systems share a common evolutionary origin. Front Endocrinol. 2011;2:16.
17.
Roch GJ, Busby ER, Sherwood NM. Evolution of GnRH: diving deeper. Gen Comp Endocrinol. 2011;171(1):1–16.
18.
Hauser F, Grimmelikhuijzen CJ. Evolution of the AKH/corazonin/ACP/GnRH receptor superfamily and their ligands in the Protostomia. Gen Comp Endocrinol. 2014;209:35–49.
19.
Jekely G. Global view of the evolution and diversity of metazoan neuropeptide signaling. Proc Natl Acad Sci U S A. 2013;110(21):8702–7.
20.
Tian S, Zandawala M, Beets I, Baytemur E, Slade SE, Scrivens JH, et al. Urbilaterian origin of paralogous GnRH and corazonin neuropeptide signalling pathways. Sci Rep. 2016;6:28788.
21.
Zandawala M, Tian S, Elphick MR. The evolution and nomenclature of GnRH-type and corazonin-type neuropeptide signaling systems. Gen Comp Endocrinol. 2018;264:64–77.
22.
Kubrak OI, Lushchak OV, Zandawala M, Nassel DR. Systemic corazonin signalling modulates stress responses and metabolism in Drosophila. Open Biol. 2016;6(11):160152.
23.
Tsai PS. Gonadotropin-releasing hormone by any other name would smell as sweet. Gen Comp Endocrinol. 2018;264:58–63.
24.
Iwakoshi E, Takuwa-Kuroda K, Fujisawa Y, Hisada M, Ukena K, Tsutsui K, et al. Isolation and characterization of a GnRH-like peptide from Octopus vulgaris. Biochem Biophys Res Commun. 2002;291(5):1187–93.
25.
Johnson JI, Kavanaugh SI, Nguyen C, Tsai PS. Localization and functional characterization of a novel adipokinetic hormone in the mollusk, Aplysia californica. PLoS One. 2014;9(8):e106014.
26.
Li S, Hauser F, Skadborg SK, Nielsen SV, Kirketerp-Moller N, Grimmelikhuijzen CJ. Adipokinetic hormones and their G protein-coupled receptors emerged in Lophotrochozoa. Sci Rep. 2016;6:32789.
27.
Dubos MP, Bernay B, Favrel P. Molecular characterization of an adipokinetic hormone-related neuropeptide (AKH) from a mollusk. Gen Comp Endocrinol. 2017;243:15–21.
28.
Kim MA, Markkandan K, Han NY, Park JM, Lee JS, Lee H, et al. Neural ganglia transcriptome and peptidome associated with sexual maturation in female pacific abalone (Haliotis discus hannai). Genes. 2019;10(4):268.
29.
Kanda A, Takahashi T, Satake H, Minakata H. Molecular and functional characterization of a novel gonadotropin-releasing-hormone receptor isolated from the common octopus (Octopus vulgaris). Biochem J. 2006;395(1):125–35.
30.
Zhang L, Tello JA, Zhang W, Tsai PS. Molecular cloning, expression pattern, and immunocytochemical localization of a gonadotropin-releasing hormone-like molecule in the gastropod mollusk, Aplysia californica. Gen Comp Endocrinol. 2008;156(2):201–9.
31.
Sun B, Kavanaugh SI, Tsai PS. Gonadotropin-releasing hormone in protostomes: insights from functional studies on Aplysia californica. Gen Comp Endocrinol. 2012;176(3):321–6.
32.
Bigot L, Zatylny-Gaudin C, Rodet F, Bernay B, Boudry P, Favrel P. Characterization of GnRH-related peptides from the pacific oyster Crassostrea gigas. Peptides. 2012;34(2):303–10.
33.
Song Y, Miao J, Cai Y, Pan L. Molecular cloning, characterization, and expression analysis of a gonadotropin-releasing hormone-like cDNA in the clam, Ruditapes philippinarum. Comp Biochem Physiol B Biochem Mol Biol. 2015;189:47–54.
34.
Nagasawa K, Osugi T, Suzuki I, Itoh N, Takahashi KG, Satake H, et al. Characterization of GnRH-like peptides from the nerve ganglia of Yesso scallop, Patinopecten yessoensis. Peptides. 2015;71:202–10.
35.
Kavanaugh SI, Tsai PS. Functional authentication of a novel gastropod gonadotropin-releasing hormone receptor reveals unusual features and evolutionary insight. PLoS One. 2016;11(7):e0160292.
36.
Kim TH, Kim MA, Kim KS, Kim JW, Lim HK, Lee JS, et al. Characterization and spatiotemporal expression of gonadotropin-releasing hormone in the Pacific abalone, Haliotis discus hannai. Comp Biochem Physiol Mol Integr Physiol. 2017;209:1–9.
37.
Sharker MR, Kim SC, Sumi KR, Sukhan ZP, Sohn YC, Lee WK, et al. Characterization and expression analysis of a GnRH-like peptide in the Pacific abalone, Haliotis discus hannai. Agri Gene. 2020;15:100099.
38.
Sharker MR, Sukhan ZP, Kim SC, Lee WK, Kho KH. Molecular identification, characterization, and expression analysis of a Gonadotropin-Releasing Hormone Receptor (GnRH-R) in pacific abalone, Haliotis discus hannai. Molecules. 2020;25(12):2733.
39.
Nagasawa K, Matsubara S, Satake H, Osada M. Functional characterization of an invertebrate gonadotropin-releasing hormone receptor in the Yesso scallop Mizuhopecten yessoensis. Gen Comp Endocrinol. 2019;282:113201.
40.
Dunn CW, Hejnol A, Matus DQ, Pang K, Browne WE, Smith SA, et al. Broad phylogenomic sampling improves resolution of the animal tree of life. Nature. 2008;452(7188):745–9.
41.
Simakov O, Marletaz F, Cho SJ, Edsinger-Gonzales E, Havlak P, Hellsten U, et al. Insights into bilaterian evolution from three spiralian genomes. Nature. 2013;493(7433):526–31.
42.
Naor Z, Huhtaniemi I. Interactions of the GnRH receptor with heterotrimeric G proteins. Front Neuroendocrinol. 2013;34(2):88–94.
43.
Krsmanovic LZ, Mores N, Navarro CE, Arora KK, Catt KJ. An agonist-induced switch in G protein coupling of the gonadotropin-releasing hormone receptor regulates pulsatile neuropeptide secretion. Proc Natl Acad Sci U S A. 2003;100(5):2969–74.
44.
Stojilkovic SS, Catt KJ. Expression and signal transduction pathways of gonadotropin-releasing hormone receptors. Recent Prog Horm Res. 1995;50:161–205.
45.
Flanagan CA, Manilall A. Gonadotropin-Releasing Hormone (GnRH) receptor structure and GnRH binding. Front Endocrinol. 2017;8:274.
46.
Cheng CK, Leung PC. Molecular biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and their receptors in humans. Endocr Rev. 2005;26(2):283–306.
47.
Sefideh FA, Moon MJ, Yun S, Hong SI, Hwang JI, Seong JY. Local duplication of Gonadotropin-Releasing Hormone (GnRH) receptor before two rounds of whole genome duplication and origin of the mammalian GnRH receptor. PLoS One. 2014;9(2):e87901.
48.
Sakai T, Yamamoto T, Matsubara S, Kawada T, Satake H. Invertebrate gonadotropin-releasing hormone receptor signaling and its relevant biological actions. Int J Mol Sci. 2020;21(22):8544.
49.
Tsai PS, Sun B, Rochester JR, Wayne NL. Gonadotropin-releasing hormone-like molecule is not an acute reproductive activator in the gastropod, Aplysia californica. Gen Comp Endocrinol. 2010;166(2):280–8.
50.
Kim MA, Rhee JS, Kim TH, Lee JS, Choi AY, Choi BS, et al. Alternative splicing profile and sex-preferential gene expression in the female and male pacific abalone Haliotis discus hannai. Genes. 2017;8(3):99.
51.
Kim KS, Kim MA, Park K, Sohn YC. NPF activates a specific NPF receptor and regulates food intake in Pacific abalone Haliotis discus hannai. Sci Rep. 2021;11(1):20912.
52.
Krogh A, Larsson B, von Heijne G, Sonnhammer EL. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol. 2001;305(3):567–80.
53.
Petersen TN, Brunak S, von Heijne G, Nielsen H. SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods. 2011;8(10):785–6.
54.
Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013;30(4):772–80.
55.
Plachetzki DC, Tsai PS, Kavanaugh SI, Sower SA. Ancient origins of metazoan gonadotropin-releasing hormone and their receptors revealed by phylogenomic analyses. Gen Comp Endocrinol. 2016;234:10–9.
56.
Thiel D, Yanez-Guerra LA, Franz-Wachtel M, Hejnol A, Jekely G. Nemertean, brachiopod, and phoronid neuropeptidomics reveals ancestral spiralian signaling systems. Mol Biol Evol. 2021;38(11):4847–66.
57.
Capella-Gutierrez S, Silla-Martinez JM, Gabaldon T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics. 2009;25(15):1972–3.
58.
Trifinopoulos J, Nguyen LT, von Haeseler A, Minh BQ, W-IQ-TREE . W-IQ-TREE: a fast online phylogenetic tool for maximum likelihood analysis. Nucleic Acids Res. 2016;44(W1):W232–5.
59.
Mirdita M, Schütze K, Moriwaki Y, Heo L, Ovchinnikov S, Steinegger M. ColabFold: making protein folding accessible to all. Nat Methods. 2022;19(6):679–82.
60.
Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583–9.
61.
Zhou P, Jin B, Li H, Huang S-Y. HPEPDOCK: a web server for blind peptide–protein docking based on a hierarchical algorithm. Nucleic Acids Res. 2018;46(W1):W443–W450.
62.
Alford RF, Leaver-Fay A, Jeliazkov JR, O’Meara MJ, DiMaio FP, Park H, et al. The Rosetta all-atom energy function for macromolecular modeling and design. J Chem Theor Comput. 2017;13(6):3031–48.
63.
Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, et al. The MIQE Guidelines: M inimum I nformation for Publication of Q uantitative Real-Time PCR E xperiments. Oxford University Press; 2009.
64.
Yoon S, Kim MA, Lee JS, Sohn YC. Functional analysis of LFRFamide signaling in Pacific abalone, Haliotis discus hannai. PLoS One. 2022;17(5):e0267039.
65.
Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29(9):e45.
66.
Kim KS, Kim TH, Kim MA, Lee JS, Sohn YC. Expression profile and reproductive regulation of APGWamide in Pacific abalone (Haliotis discus hannai). Comp Biochem Physiol Mol Integr Physiol. 2018;222:26–35.
67.
Colas P, Dubé F. Meiotic maturation in mollusc oocytes, Seminars in Cell & Developmental Biology. Elsevier; 1998. p. 539–48.
68.
Nam BH, Kwak W, Kim YO, Kim DG, Kong HJ, Kim WJ, et al. Genome sequence of pacific abalone (Haliotis discus hannai): the first draft genome in family Haliotidae. Gigascience. 2017;6(5):1–8.
69.
Mirzadegan T, Benkö G, Filipek S, Palczewski K. Sequence analyses of G-protein-coupled receptors: similarities to rhodopsin. Biochemistry. 2003;42(14):4310–67.
70.
Velentza A, Spiliou S, Poulos CP, Goldsworthy GJ. Synthesis and biological activity of adipokinetic hormone analogues with modifications in the 4-8 region. Peptides. 2000;21(5):631–7.
71.
Yerushalmi Y, Bhargava K, Gilon C, Pener MP. Structure-activity relations of the dark-colour-inducing neurohormone of locusts. Insect Biochem Mol Biol. 2002;32(8):909–17.
72.
Caers J, Peeters L, Janssen T, De Haes W, Gade G, Schoofs L. Structure-activity studies of Drosophila Adipokinetic Hormone (AKH) by a cellular expression system of dipteran AKH receptors. Gen Comp Endocrinol. 2012;177(3):332–7.
73.
Sakai T, Shiraishi A, Kawada T, Matsubara S, Aoyama M, Satake H. Invertebrate gonadotropin-releasing hormone-related peptides and their receptors: an update. Front Endocrinol. 2017;8:217.
74.
Andreatta G, Broyart C, Borghgraef C, Vadiwala K, Kozin V, Polo A, et al. Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in Platynereis. Proc Natl Acad Sci U S A; 2019.
75.
Sugnet CW, Srinivasan K, Clark TA, O'Brien G, Cline MS, Wang H, et al. Unusual intron conservation near tissue-regulated exons found by splicing microarrays. PLoS Comput Biol. 2006;2(1):e4.
76.
Yang J, Huang H, Yang H, He X, Jiang X, Shi Y, et al. Specific activation of the G protein-coupled receptor BNGR-A21 by the neuropeptide corazonin from the silkworm, Bombyx mori, dually couples to the G(q) and G(s) signaling cascades. J Biol Chem. 2013;288(17):11662–75.
77.
Markovic D, Challiss RA. Alternative splicing of G protein-coupled receptors: physiology and pathophysiology. Cell Mol Life Sci. 2009;66(20):3337–52.
78.
Marti-Solano M, Crilly SE, Malinverni D, Munk C, Harris M, Pearce A, et al. Combinatorial expression of GPCR isoforms affects signalling and drug responses. Nature. 2020;587(7835):650–6.
79.
Berridge MJ. Inositol trisphosphate and calcium signalling mechanisms. Biochim Biophys Acta. 2009;1793(6):933–40.
80.
Oh DY, Song JA, Moon JS, Moon MJ, Kim JI, Kim K, et al. Membrane-proximal region of the carboxyl terminus of the Gonadotropin-Releasing Hormone Receptor (GnRHR) confers differential signal transduction between mammalian and nonmammalian GnRHRs. Mol Endocrinol. 2005;19(3):722–31.
81.
Tello JA, Rivier JE, Sherwood NM. Tunicate Gonadotropin-Releasing Hormone (GnRH) peptides selectively activate Ciona intestinalis GnRH receptors and the green monkey type II GnRH receptor. Endocrinology. 2005;146(9):4061–73.
82.
Tello JA, Sherwood NM. Amphioxus: beginning of vertebrate and end of invertebrate type GnRH receptor lineage. Endocrinology. 2009;150(6):2847–56.
83.
Arora KK, Sakai A, Catt KJ. Effects of second intracellular loop mutations on signal transduction and internalization of the gonadotropin-releasing hormone receptor. J Biol Chem. 1995;270(39):22820–6.
84.
Myburgh DB, Millar RP, Hapgood JP. Alanine-261 in intracellular loop III of the human gonadotropin-releasing hormone receptor is crucial for G-protein coupling and receptor internalization. Biochem J. 1998 May 1;331(Pt 3):893–6.
85.
Arora KK, Krsmanovic LZ, Mores N, O'Farrell H, Catt KJ. Mediation of cyclic AMP signaling by the first intracellular loop of the gonadotropin-releasing hormone receptor. J Biol Chem. 1998;273(40):25581–6.
86.
Millar RP, Lu ZL, Pawson AJ, Flanagan CA, Morgan K, Maudsley SR. Gonadotropin-releasing hormone receptors. Endocr Rev. 2004;25(2):235–75.
87.
Pfleger KD, Bogerd J, Millar RP. Conformational constraint of mammalian, chicken, and salmon GnRHs, but not GnRH II, enhances binding at mammalian and nonmammalian receptors: evidence for preconfiguration of GnRH II. Mol Endocrinol. 2002;16(9):2155–62.
88.
López de Maturana R, Pawson AJ, Lu Z-L, Davidson L, Maudsley S, Morgan K, et al. Gonadotropin-releasing hormone analog structural determinants of selectivity for inhibition of cell growth: support for the concept of ligand-induced selective signaling. Mol Endocrinol. 2008;22(7):1711–22.
89.
Iwakoshi-Ukena E, Ukena K, Takuwa-Kuroda K, Kanda A, Tsutsui K, Minakata H. Expression and distribution of octopus gonadotropin-releasing hormone in the central nervous system and peripheral organs of the octopus (Octopus vulgaris) by in situ hybridization and immunohistochemistry. J Comp Neurol. 2004;477(3):310–23.
90.
Fodor I, Zrinyi Z, Horvath R, Urban P, Herczeg R, Buki G, et al. Identification, presence, and possible multifunctional regulatory role of invertebrate gonadotropin-releasing hormone/corazonin molecule in the great pond snail (Lymnaea stagnalis). Gen Comp Endocrinol. 2020;299:113621.
91.
Veenstra JA. Does corazonin signal nutritional stress in insects?Insect Biochem Mol Biol. 2009;39(11):755–62.
92.
Roller L, Tanaka Y, Tanaka S. Corazonin and corazonin-like substances in the central nervous system of the Pterygote and Apterygote insects. Cell Tissue Res. 2003;312(3):393–406.
93.
Rodet F, Lelong C, Dubos MP, Favrel P. Alternative splicing of a single precursor mRNA generates two subtypes of Gonadotropin-Releasing Hormone receptor orthologues and their variants in the bivalve mollusc Crassostrea gigas. Gene. 2008;414(1–2):1–9.
94.
Bablanian GM, Weiss KR, Kupfermann I. Motor control of the appetitive phase of feeding behavior in Aplysia. Behav Neural Biol. 1987;48(3):394–407.
95.
Nagasawa K, Muroi K, Thitiphuree T, Minegishi Y, Itoh N, Osada M. Cloning of invertebrate Gonadotropin-Releasing Hormone Receptor (GnRHR)-like gene in Yesso scallop, Patinopecten yessoensis. Agri Gene. 2017;3:46–56.
96.
York PS, Cummins SF, Degnan SM, Woodcroft BJ, Degnan BM. Identification of genes differentially expressed in the ganglia of growing Haliotis asinina. J Shellfish Res. 2010;29(3):741–52.
97.
Lyu M, Gao X, Zhang M, Lin S, Su Y, Luo X, et al. Development of a feeding strategy for Haliotis discus hannai♀× Haliotis fulgens♂ hybrids and parental H. discus hannai. Aquaculture. 2022;554:738158.
98.
Nuurai P, Cummins SF, Botwright NA, Sobhon P. Characterization of an abalone gonadotropin-releasing hormone and its effect on ovarian cell proliferation. Aquaculture. 2016;450:116–22.
99.
Sharker MR, Sukhan ZP, Kim SC, Hossen S, Cho Y, Choi CY, et al. In vivo effects of GnRH peptide on gonadal proliferation and related gene expression of Pacific abalone, Haliotis discus hannai. Aquaculture. 2021;531:735911.
100.
Treen N, Itoh N, Miura H, Kikuchi I, Ueda T, Takahashi KG, et al. Mollusc gonadotropin-releasing hormone directly regulates gonadal functions: a primitive endocrine system controlling reproduction. Gen Comp Endocrinol. 2012;176(2):167–72.
101.
Nagasawa K, Oouchi H, Itoh N, Takahashi KG, Osada M. In vivo administration of scallop GnRH-like peptide influences on gonad development in the Yesso scallop, Patinopecten yessoensis. PLoS One. 2015;10(6):e0129571.
102.
Chiba A, Sohn YC, Honma Y. Distribution of neuropeptide Y and gonadotropin-releasing hormone immunoreactivities in the brain and hypophysis of the ayu, Plecoglossus altivelis (Teleostei). Arch Histol Cytol. 1996;59(2):137–48.
103.
Kobayashi M, Amano M, Kim M-H, Furukawa K, Hasegawa Y, Aida K. Gonadotropin-releasing hormones of terminal nerve origin are not essential to ovarian development and ovulation in goldfish. Gen Comp Endocrinol. 1994;95(2):192–200.
104.
Kamiya C, Ohta N, Ogura Y, Yoshida K, Horie T, Kusakabe TG, et al. Nonreproductive role of gonadotropin-releasing hormone in the control of ascidian metamorphosis. Dev Dyn. 2014;243(12):1524–35.
105.
Kauffman AS, Rissman EF. The evolutionarily conserved gonadotropin-releasing hormone II modifies food intake. Endocrinology. 2004;145(2):686–91.
106.
Nishiguchi R, Azuma M, Yokobori E, Uchiyama M, Matsuda K. Gonadotropin-releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio. Front Endocrinol. 2012;3:122.
107.
Zhao Y, Bretz CA, Hawksworth SA, Hirsh J, Johnson EC. Corazonin neurons function in sexually dimorphic circuitry that shape behavioral responses to stress in Drosophila. PLoS One. 2010;5(2):e9141.
108.
Konuma T, Morooka N, Nagasawa H, Nagata S. Knockdown of the adipokinetic hormone receptor increases feeding frequency in the two-spotted cricket Gryllus bimaculatus. Endocrinology. 2012;153(7):3111–22.
