{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:41:21Z","timestamp":1793421681959,"version":"4.5.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Experiments were carried out to determine whether, as with other mollusks that have been studied, the snail,<jats:italic>Lymnaea stagnalis<\/jats:italic>, can absorb, esterify and store vertebrate steroids that are present in the water. We also carried out experiments to determine whether neural tissues of the snail could be immunohistochemically stained with an antibody to human aromatase (a key enzyme that catalyzes the conversion of testosterone [T] to 17\u03b2-estradiol [E<jats:sub>2<\/jats:sub>]); and, if so, to determine the significance of such staining. Previous studies on other mollusks have reported such staining and have proposed this as decisive evidence that mollusks have the same steroid synthesis pathway as vertebrates. We found that snails absorb, esterify and retain esterified T, E<jats:sub>2<\/jats:sub>, progesterone and ethinyl-estradiol (albeit with an absorption rate about four times slower, on a weight basis, than the mussel,<jats:italic>Mytilus edulis<\/jats:italic>). We also found that not only anti-human aromatase, but also anti-human nuclear progesterone receptor (nPR) and anti-human gonadotropin-releasing hormone antibodies immunohistochemically stained snail neural cells. However, further experiments, involving gel electrophoretic separation, followed by immunostaining, of proteins extracted from the neural tissue, found at least two positively-stained bands for each antibody, none of which had masses matching the human proteins to which the antibodies had been raised. The anti-aromatase antibody even stained the 140 kDA ladder protein used as a molecular weight marker on the gels. Mass spectrometric analysis of the bands did not find any peptide sequences that corresponded to the human proteins. Our findings confirm that the presence of vertebrate-like sex steroids in molluscan tissues is not necessarily evidence of endogenous origin. The results also show that immunohistochemical studies using antibodies against human proteins are grossly non-specific and likely to have little or no value in studying steroid synthesis or activity in mollusks. Our conclusions are consistent with the fact that genes for aromatase and nPR have not been found in the genome of the snail or of any other mollusk. Our overarching conclusion, from this and our previous studies, is that the endocrinology of mollusks is not the same as that of humans or any other vertebrates and that continuing to carry out physiological and ecotoxicological studies on mollusks on the basis of this false assumption, is an unconscionable waste of resources.<\/jats:p>","DOI":"10.3389\/fendo.2022.981564","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T06:57:24Z","timestamp":1662620244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Studies on a widely-recognized snail model species (Lymnaea stagnalis) provide further evidence that vertebrate steroids do not have a hormonal role in the reproduction of mollusks"],"prefix":"10.3389","volume":"13","author":[{"given":"Istv\u00e1n","family":"Fodor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"Kiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antal","family":"Tapodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex R. O.","family":"Cousins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Katsiadaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander P.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Pirger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2012.11.006","article-title":"Do mollusks use vertebrate sex steroids as reproductive hormones? II. critical review of the evidence that steroids have biological effects","volume":"78","author":"Scott","year":"2013","journal-title":"Steroids"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2012.08.009","article-title":"Do mollusks use vertebrate sex steroids as reproductive hormones? Part i. critical appraisal of the evidence for the presence, biosynthesis and uptake of steroids","volume":"77","author":"Scott","year":"2012","journal-title":"Steroids"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2020.110949","article-title":"A critical evaluation of some of the recent so-called \u2018Evidence\u2019 for the involvement of vertebrate-type sex steroids in the reproduction of mollusks","volume":"516","author":"Fodor","year":"2020","journal-title":"Mol Cell Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.ygcen.2018.04.005","article-title":"Is there any value in measuring vertebrate steroids in invertebrates","volume":"265","author":"Scott","year":"2018","journal-title":"Gen Comp Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2010.12.009","article-title":"Biosynthesis and metabolism of steroids in molluscs","volume":"127","author":"Fernandes","year":"2011","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2013.08.003","article-title":"Esterification of vertebrate like steroids in molluscs: A target of endocrine disruptors","volume":"158","author":"Giusti","year":"2013","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10646-006-0110-4","article-title":"Sex steroids and potential mechanisms of non-genomic endocrine disruption in invertebrates","volume":"16","author":"Janer","year":"2007","journal-title":"Ecotoxicology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2004.07.002","article-title":"Estrogen synthesis in relation to gonadal development of Japanese scallop, Patinopecten yessoensis: Gonadal profile and immunolocalization of P450 aromatase and estrogen","volume":"139","author":"Osada","year":"2004","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/jez.a.10276","article-title":"Vitellogenin synthesis in the ovary of scallop, Patinopecten yessoensis: Control by estradiol-17\u03b2 and the central nervous system","volume":"299","author":"Osada","year":"2003","journal-title":"J Exp Zool A Comp Exp Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/ar.24075","article-title":"The mussel Mytilus galloprovincialis in the bay of Naples: New insights on oogenic cycle and its hormonal control","volume":"302","author":"Rosati","year":"2019","journal-title":"Anat Rec"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/ar.23626","article-title":"Spermatogenic cycle and steroidogenic control of spermatogenesis in Mytilus galloprovincialis collected in the bay of Naples","volume":"300","author":"Prisco","year":"2017","journal-title":"Anat Rec"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0305-0491(97)00233-2","article-title":"Gonadal estrogen profile and immunohistochemical localization of steroidogenic enzymes in the oyster and scallop during sexual maturation","volume":"118","author":"Matsumoto","year":"1997","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s00360-008-0256-x","article-title":"Immunolocalization of cholesterol side chain cleavage enzyme (P450scc) in Mytilus galloprovincialis and its induction by nutritional levels","volume":"178","author":"Martinez","year":"2008","journal-title":"J Comp Physiol B Biochem Syst Environ"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.10014","article-title":"A estradiol-17\u03b2 receptor in the reproductive system of the female of Octopus vulgaris: Characterization and immunolocalization","volume":"61","author":"Di Cosmo","year":"2002","journal-title":"Mol Reprod Dev"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2016.08.007","article-title":"Mussels (Mytilus spp.) display an ability for rapid and high capacity uptake of the vertebrate steroid, estradiol-17\u03b2 from water","volume":"165","author":"Schwarz","year":"2017","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.jsbmb.2017.02.016","article-title":"Rapid uptake, biotransformation, esterification and lack of depuration of testosterone and its metabolites by the common mussel, Mytilus spp","volume":"171","author":"Schwarz","year":"2017","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jsbmb.2017.10.016","article-title":"Uptake and metabolism of water-borne progesterone by the mussel, Mytilus spp. (Mollusca)","volume":"178","author":"Schwarz","year":"2018","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.794623","article-title":"The uptake of ethinyl-estradiol and cortisol from water by mussels (Mytilus spp.)","volume":"12","author":"Katsiadaki","year":"2021","journal-title":"Front Endocrinol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1006\/gcen.2001.7630","article-title":"Biotransformation and disposition of testosterone in the Eastern mud snail Ilyanassa obsoleta","volume":"122","author":"Gooding","year":"2001","journal-title":"Gen Comp Endocrinol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/45.1.81","article-title":"Testosterone-fatty acid esterification: A unique target for the endocrine toxicity of tributyltin to gastropods","volume":"45","author":"Leblanc","year":"2005","journal-title":"Integ Comp Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2006.10.003","article-title":"Identification of the steroid fatty acid ester conjugates formed in vivo in Mytilus edulis as a result of exposure to estrogens","volume":"72","author":"Labadie","year":"2007","journal-title":"Steroids"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2006.07.006","article-title":"Laboratory exposure to 17\u03b2-estradiol fails to induce vitellogenin and estrogen receptor gene expression in the marine invertebrate Mytilus edulis","volume":"79","author":"Puinean","year":"2006","journal-title":"Aquat Toxicol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2003.12.002","article-title":"Esterification of vertebrate-type steroids in the Eastern oyster (Crassostrea virginica)","volume":"69","author":"Janer","year":"2004","journal-title":"Steroids"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2004.11.024","article-title":"Testosterone conjugating activities in invertebrates: Are they targets for endocrine disruptors","volume":"71","author":"Janer","year":"2005","journal-title":"Aquat Toxicol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.aquatox.2015.05.018","article-title":"Progesterone is actively metabolized to 5\u03b1-Pregnane-3,20-Dione and 3\u03b2-Hydroxy-5\u03b1-Pregnan-20-One by the marine mussel Mytilus galloprovincialis","volume":"165","author":"Dimastrogiovanni","year":"2015","journal-title":"Aquat Toxicol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.chemosphere.2007.04.082","article-title":"Profiles of environmental and endogenous estrogens in the zebra mussel Dreissena polymorpha","volume":"69","author":"Peck","year":"2007","journal-title":"Chemosphere"},{"key":"B27","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.steroids.2017.05.008","article-title":"Analysis of testosterone fatty acid esters in the digestive gland of mussels by liquid chromatography-high resolution mass spectrometry","volume":"123","author":"Guercia","year":"2017","journal-title":"Steroids"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/etc.2234","article-title":"Testosterone levels and fecundity in the hermaphroditic aquatic snail Lymnaea stagnalis exposed to testosterone and endocrine disruptors","volume":"32","author":"Giusti","year":"2013","journal-title":"Environ Toxicol Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jembe.2005.04.027","article-title":"Short-term bioaccumulation, circulation and metabolism of estradiol-17\u03b2 in the oyster","volume":"325","author":"Le Curieux-Belfond","year":"2005","journal-title":"Crassostrea gigas J Exp Mar Biol Ecol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2116\/bunsekikagaku.50.247","article-title":"Identification and quantitation of steroid hormones in marine gastropods by GC\/MS","volume":"50","author":"Lu","year":"2001","journal-title":"Bunseki Kagaku"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2007.05.003","article-title":"Natural and synthetic endocrine disrupting compounds (Edcs) in water, sediment and biota of a coastal lagoon","volume":"33","author":"Pojana","year":"2007","journal-title":"Environ Int"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2015.09.013","article-title":"LC-MS measurment of free steroids in mussels (Mytilus trossulus) from the southern Baltic Sea","volume":"117","author":"Hallmann","year":"2016","journal-title":"J Pharm BioMed"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2020.109316","article-title":"Concentrations levels and effects of 17\u03b1-ethinylestradiol in freshwater and marine waters and bivalves: A review","volume":"185","author":"Almeida","year":"2020","journal-title":"Environ Res"},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.1201\/9781003029854-8","article-title":"A critical review of sex steroid hormones and the induction mechanisms of imposex in gastropod mollusks","volume-title":"Advances in invertebrate (Neuro)Endocrinology","author":"Horiguchi","year":"2020"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2019.05.004","article-title":"Estrogenic compounds as exogenous modulators of physiological functions in molluscs: Signaling pathways and biological responses","volume":"222","author":"Balbi","year":"2019","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.903575","article-title":"From dark to light - an overview of over 70 years of endocrine disruption research on marine mollusks","volume":"13","author":"Fodor","year":"2022","journal-title":"Front Endocrinol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"69","DOI":"10.4002\/040.064.0103","article-title":"Neuronal transcriptome analysis of a widely recognised molluscan model organism highlights the absence of key proteins involved in the de novo synthesis and receptor-mediation of sex steroids in vertebrates","volume":"64","author":"Fodor","year":"2021","journal-title":"Malacologia"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56962","article-title":"The unlimited potential of the great pond snail, Lymnaea stagnalis","volume":"9","author":"Fodor","year":"2020","journal-title":"eLife"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glab014","article-title":"The great pond snail (Lymnaea stagnalis) as a model of ageing and age-related memory impairment: An overview","volume":"76","author":"Fodor","year":"2021","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.scitotenv.2019.03.035","article-title":"Lymnaea stagnalis as a freshwater model invertebrate for ecotoxicological studies","volume":"669","author":"Amorim","year":"2019","journal-title":"Sci Total Environ"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2010.00167","article-title":"Neuro-endocrine control of reproduction in hermaphroditic freshwater snails: Mechanisms and evolution","volume":"4","author":"Koene","year":"2010","journal-title":"Front Behav Neurosci"},{"key":"B42","doi-asserted-by":"crossref","DOI":"10.1093\/oxfordhb\/9780190456757.013.26","article-title":"Neurobiology of reproduction in mollusks: Mechanisms and evolution","volume-title":"The Oxford handbook of invertebrate neurobiology","author":"Di Cristo","year":"2017"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2019.11.020","article-title":"Lymnaea stagnalis as model for translational neuroscience research: From pond to bench","volume":"108","author":"Rivi","year":"2020","journal-title":"Neurosci Biobehav Rev"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12716","article-title":"What can we teach Lymnaea and what can Lymnaea teach us","volume":"96","author":"Rivi","year":"2021","journal-title":"Biol Rev Camb Philos Soc"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/9780470015902.a0029277","article-title":"Molluscan nervous systems","volume":"2","author":"Benjamin","year":"2021","journal-title":"eLS"},{"key":"B46","doi-asserted-by":"crossref","first-page":"33","DOI":"10.5772\/intechopen.72216","article-title":"Pond snail reproduction as model in the environmental risk assesment: Reality and doubts","volume-title":"Biological resources of water","author":"Pirger","year":"2018"},{"key":"B47","doi-asserted-by":"publisher","first-page":"R9","DOI":"10.1016\/j.cub.2008.10.013","article-title":"Lymnaea","volume":"19","author":"Kemenes","year":"2009","journal-title":"Curr Biol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2022.882932","article-title":"Insulin and memory in invertebrates","volume":"16","author":"Nakai","year":"2022","journal-title":"Front Behav Neurosci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2020.113621","article-title":"Identification, presence, and possible multifunctional regulatory role of invertebrate gonadotropin-releasing Hormone\/Corazonin molecule in the great pond snail (Lymnaea stagnalis)","volume":"299","author":"Fodor","year":"2020","journal-title":"Gen Comp Endocrinol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2795(199808)50:4<451::AID-MRD9>3.0.CO;2-H","article-title":"Progesterone receptor in the reproductive system of the female of Octopus vulgaris: Characterization and immunolocalization","volume":"50","author":"Di Cosmo","year":"1998","journal-title":"Mol Reprod Dev"},{"key":"B51","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.neuroscience.2008.05.003","article-title":"The presence and distribution of pituitary adenylate cyclase activating polypeptide and its receptor in the snail Helix pomatia","volume":"155","author":"Hernadi","year":"2008","journal-title":"Neurosci"},{"key":"B52","doi-asserted-by":"publisher","first-page":"10028","DOI":"10.1038\/s41598-021-89614-5","article-title":"Functional characterization and related evolutionary implications of invertebrate gonadotropin-releasing Hormone\/Corazonin in a well-established model species","volume":"11","author":"Fodor","year":"2021","journal-title":"Sci Rep"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2009.09.009","article-title":"Gonadotropin-releasing hormone-like molecule is not an acute reproductive activator in the gastropod, Aplysia californica","volume":"166","author":"Tsai","year":"2010","journal-title":"Gen Comp Endocrinol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2013.11.007","article-title":"Localization of a molluscan gonadotropin-releasing hormone in Aplysia californica by in situ hybridization and immunocytochemistry","volume":"195","author":"Jung","year":"2014","journal-title":"Gen Comp Endocrinol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/0016-6480(87)90253-x","article-title":"In vitro metabolism of androstenedione and identification of endogenous steroids in Helix aspersa","volume":"66","author":"Le Guellec","year":"1987","journal-title":"Gen Comp Endocrinol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/S0742-8413(96)00163-6","article-title":"Steroids in Achatina fulica (Bowdich): Steroid profile in haemolymph and in vitro release of steroids from endogenous precursors by ovotestis and albumen gland","volume":"116","author":"Bose","year":"1997","journal-title":"Comp Biochem Physiol C Pharmacol Toxicol"},{"key":"B57","first-page":"46","article-title":"Concentrations of steroids in the giant African land snail (Archahatina marginata) at different reproductive phases","volume":"1","author":"Bamidele","year":"2015","journal-title":"Molluscan Res"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1601778","article-title":"Origin of an ancient Hormone\/Receptor couple revealed by resurrection of an ancestral estrogen","volume":"3","author":"Markov","year":"2017","journal-title":"Sci Adv"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2011.03.022","article-title":"Evolutionary origins of the estrogen signaling system: Insights from amphioxus","volume":"127","author":"Callard","year":"2011","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-5-43","article-title":"The genomic environment around the aromatase gene: Evolutionary insights","volume":"5","author":"Castro","year":"2005","journal-title":"BMC Evol Biol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2019.110526","article-title":"Steroid receptors and vertebrate evolution","volume":"496","author":"Baker","year":"2019","journal-title":"Mol Cell Endocrinol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/0016-6480(77)90116-2","article-title":"The in vitro biosynthesis of steroids by the gonad of the cuttlefish (Sepia officinalis)","volume":"33","author":"Carreau","year":"1977","journal-title":"Gen Comp Endocrinol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0166-445X(97)00102-1","article-title":"Effects of tributyltin on the phase I testosterone metabolism and steroid titres of the clam Ruditapes decussata","volume":"42","author":"Morcillo","year":"1998","journal-title":"Aquat Toxicol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1093\/mollus\/eys001","article-title":"Detection of vertebrate-type steroid hormones and their converting activities in the neogastropod Thais clavigera (K\u00fcster, 1858)","volume":"78","author":"Goto","year":"2012","journal-title":"J Molluscan Stud"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/s0960-0760(01)00109-1","article-title":"Androgen metabolism in oyster Crassostrea gigas: Evidence for 17\u03b2-HSD activities and characterization of an aromatase-like activity inhibited by pharmacological compounds and a marine pollutant","volume":"78","author":"Le Curieux-Belfond","year":"2001","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.6953","article-title":"Aromatisation of steroids in the bivalve Mytilus trossulus","volume":"7","author":"Hallmann","year":"2019","journal-title":"PeerJ"},{"key":"B67","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jsbmb.2014.09.010","article-title":"Biological messiness vs. biological genius: Mechanistic aspects and roles of protein promiscuity","volume":"151","author":"Atkins","year":"2015","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jsbmb.2015.01.008","article-title":"Steroid promiscuity: Diversity of enzyme action. preface","volume":"151","author":"Lathe","year":"2015","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2002.6594","article-title":"Isolation and characterization of a GnRH-like peptide from Octopus vulgaris","volume":"291","author":"Iwakoshi","year":"2002","journal-title":"Biochem Biophys Res Comm"},{"key":"B70","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ygcen.2014.07.009","article-title":"Evolution of the AKH\/Corazonin\/ACP\/GnRH receptor superfamily and their ligands in the Protostomia","volume":"209","author":"Hauser","year":"2014","journal-title":"Gen Comp Endocrinol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2016.06.007","article-title":"Ancient origins of metazoan gonadotropin-releasing hormone and their receptors revealed by phylogenomic analyses","volume":"234","author":"Plachetzki","year":"2016","journal-title":"Gen Comp Endocrinol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ygcen.2017.09.010","article-title":"Gonadotropin-releasing hormone by any other name would smell as sweet","volume":"264","author":"Tsai","year":"2018","journal-title":"Gen Comp Endocrinol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2009.01852.x","article-title":"Octopus gonadotrophin-releasing hormone: A multifunctional peptide in the endocrine and nervous systems of the cephalopod","volume":"21","author":"Minakata","year":"2009","journal-title":"J Neuroendocrinol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228544","article-title":"Invertebrate gonadotropin-releasing hormone receptor signaling and its relevant biological actions","volume":"21","author":"Sakai","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.2108\/zsj.27.656","article-title":"Biochemical and immunohistochemical analyses of a GnRH-like peptide in the neural ganglia of the pacific abalone Haliotis discus hannai (Gastropoda)","volume":"27","author":"Amano","year":"2010","journal-title":"Zool Sci"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20544","article-title":"Involvement of gnrh neuron in the spermatogonial proliferation of the scallop, Patinopecten yessoensis","volume":"74","author":"Nakamura","year":"2007","journal-title":"Mol Reprod Dev"},{"key":"B77","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1006\/gcen.2000.7457","article-title":"Biological and immunological characterization of multiple GnRH in an opisthobranch mollusk, Aplysia californica","volume":"118","author":"Zhang","year":"2000","journal-title":"Gen Comp Endocrinol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/s0016-6480(02)00519-1","article-title":"Localization of gonadotropin-releasing hormone in the central nervous system and a peripheral chemosensory organ of Aplysia californica","volume":"130","author":"Tsai","year":"2003","journal-title":"Gen Comp Endocrinol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(sici)1096-9861(19980817)398:1<1::aid-cne1>3.0.co;2-5","article-title":"Neuropeptidergic control of the optic gland of Octopus vulgaris: FMRF-amide and GnRH immunoreactivity","volume":"398","author":"Di Cosmo","year":"1998","journal-title":"J Comp Neurol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812138106","article-title":"Independent elaboration of steroid hormone signaling pathways in metazoans","volume":"106","author":"Markov","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2012.0474","article-title":"The cytochrome P450 genesis locus: The origin and evolution of animal cytochrome P450s","volume":"368","author":"Nelson","year":"2013","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.653792","article-title":"Function and evolution of nuclear receptors in environmental-dependent postembryonic development","volume":"9","author":"Taubenheim","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3390\/md14020039","article-title":"Chemical diversity and biological properties of secondary metabolites from Sea hares of Aplysia genus","volume":"14","author":"Pereira","year":"2016","journal-title":"Mar Drugs"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4039(96)01894-1","article-title":"Geodisterol, a novel polyoxygenated sterol with an aromatic a ring from the tropical marine sponge Geodia sp","volume":"37","author":"Wang","year":"1996","journal-title":"Tetrahedron Lett"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1021\/np100562n","article-title":"Steroids with aromatic a-rings from the hainan soft coral Dendronephthya studeri ridley","volume":"74","author":"Yan","year":"2011","journal-title":"J Nat Prod"},{"key":"B86","doi-asserted-by":"publisher","first-page":"16439","DOI":"10.1038\/s41598-019-52850-x","article-title":"Early embryonic exposure of freshwater gastropods to pharmaceutical 5-Alpha-Reductase inhibitors results in a surprising open-coiled \u201cBanana-shaped\u201d shell","volume":"9","author":"Baynes","year":"2019","journal-title":"Sci Rep"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.981564\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,26]],"date-time":"2023-11-26T18:25:23Z","timestamp":1701023123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.981564\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,8]]},"references-count":86,"alternative-id":["10.3389\/fendo.2022.981564"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.981564","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,8]]},"article-number":"981564"}}