{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T19:38:00Z","timestamp":1772480280896,"version":"3.50.1"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006041","name":"Innovate UK","doi-asserted-by":"publisher","award":["YHF\/21865\/SM00"],"award-info":[{"award-number":["YHF\/21865\/SM00"]}],"id":[{"id":"10.13039\/501100006041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006041","name":"Innovate UK","doi-asserted-by":"publisher","award":["YHA\/21865\/SM02"],"award-info":[{"award-number":["YHA\/21865\/SM02"]}],"id":[{"id":"10.13039\/501100006041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>A new humoral factor has been detected, within a project aiming to disclose the body\u2019s reproductive hormonal brake against tissue overgrowth, micrin (\u2018my-crin\u2019). Factor purification involved fractionation of ovine and bovine ovarian follicular fluid and blood plasma and serum, with evaluation via rat bioassays in vivo and in vitro. Analysis averse, the molecular effector provided a chemical conundrum. Evidence from mass spectrometry (MS) is problematic, with spectra from MALDI-TOF, the only productive MS modality, confused by a target polypeptide exhibiting artefacts during processing, storage and MALDI set-up in terms of C-terminal truncation and water losses, along with dimerization (C-terminally truncated fragments doubled up). Evidence from chemical sequencing of amino acid (aa) residues is likewise confusing, but consistent with a spiralised depolymerisation within the Edman reaction chamber of a unitary polypeptide. Data decryption has overcome molecular intractability, supported by the results of tryptic digestion and epitope mapping using immunohistochemistry (IHC). The detected inhibitory factor relates to secretogranin II (SgII), the neurosecretory prohormone, in the form of a secreted acidic 70-aa polypeptide derivative called here SgII-70 (\u2018sig two seventy\u2019). The product of peptide splicing, micrin\/SgII-70 is a twisted amphipathic molecule, with ends entwined (via salt bridging), the complex knotted structure confounding Edman and MALDI analyses, as well as computational molecular modelling, whilst conferring protease and heat resistance. Hexapeptide mimetics simulating both ends of the hormone together have been demonstrated in different species and settings in antiorganotrophism (tissue reduction via fewer, smaller cells) and reproductive modulation (more offspring). There are potential clinical applications for agonists in tissue overgrowth conditions such as endometriosis, PCOS, BPH and cancer, and for micrin antagonists in infertility.<\/jats:p>","DOI":"10.1371\/journal.pone.0340980","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T18:31:20Z","timestamp":1772476280000},"page":"e0340980","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Detecting the body\u2019s reproductive hormonal brake against tissue overgrowth: Micrin\/SgII-70"],"prefix":"10.1371","volume":"21","author":[{"given":"John E.","family":"Hart","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6060-2394","authenticated-orcid":true,"given":"Keith G.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher R.","family":"Mundy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurelia C.","family":"Hart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Howlett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell P.","family":"Newton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"issue":"2","key":"pone.0340980.ref001","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0163-7258(90)90087-I","article-title":"Endocrine pathology of estrogens: species differences","volume":"47","author":"JE Hart","year":"1990","journal-title":"Pharmacol Ther"},{"issue":"1957","key":"pone.0340980.ref002","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1126\/science.76.1957.19","article-title":"Dual Endocrine Activity of the Testes","volume":"76","author":"DR McCullagh","year":"1932","journal-title":"Science"},{"issue":"2","key":"pone.0340980.ref003","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0300-483X(90)90019-D","article-title":"Pituitary-related weight changes affecting the liver, uterus and adrenal glands of rats treated with hexoestrol and clomiphene in high doses","volume":"61","author":"JE Hart","year":"1990","journal-title":"Toxicology"},{"issue":"5","key":"pone.0340980.ref004","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1210\/endo-25-5-793","article-title":"Properties of Ovarian Extracts","volume":"25","author":"HW Marlow","year":"1939","journal-title":"Endocrinology"},{"key":"pone.0340980.ref005","first-page":"7","article-title":"The effect of continued oral administration of stilbestrol on body growth and organ weights of adult uncastrated and castrated female rats","volume":"6","author":"CS Matthews","year":"1942","journal-title":"Growth"},{"issue":"2","key":"pone.0340980.ref006","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1210\/endo-40-2-116","article-title":"Increased pituitary and adrenal weight produced by estrone in intact and castrated normal and runt rats","volume":"40","author":"OW Smith","year":"1947","journal-title":"Endocrinology"},{"issue":"6","key":"pone.0340980.ref007","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.mehy.2014.10.009","article-title":"The body has a brake: micrin is a postulated new gonadal hormone curbing tissue overgrowth and restricting reproduction","volume":"83","author":"JE Hart","year":"2014","journal-title":"Med Hypotheses"},{"key":"pone.0340980.ref008","first-page":"189","article-title":"In chromatographic and electrophoretic techniques.","volume-title":"Chromatography","author":"D. 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