{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:59:47Z","timestamp":1792119587283,"version":"4.4.0"},"reference-count":49,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Welcome Trust","doi-asserted-by":"crossref","award":["212242\/Z\/18\/Z to A.E.H."],"award-info":[{"award-number":["212242\/Z\/18\/Z to A.E.H."]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Vice Chancellor's and Newnham College Scholarship"},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite the importance of the mouse in biomedical research, the levels of circulating gonadal steroids across the estrous cycle are not established with any temporal precision. Using liquid chromatography\u2013mass spectrometry, now considered the gold standard for steroid hormone analysis, we aimed to generate a detailed profile of gonadal steroid levels across the estrous cycle of C57BL\/6J mice. For reference, luteinizing hormone (LH) and prolactin concentrations were measured in the same samples by sandwich enzyme-linked immunosorbent assay. Terminal blood samples were collected at 8-hour intervals (10 Am, 6 Pm, 2 Am) throughout the 4 stages of the estrous cycle. As expected, the LH surge was detected at 6 Pm on proestrus with a mean (\u00b1SEM) concentration of 11 \u00b1 3\u2005ng\/mL and occurred coincident with the peak in progesterone levels (22 \u00b1 4\u2005ng\/mL). Surprisingly, estradiol concentrations peaked at 10 Am on diestrus (51 \u00b1 8\u2005pg\/mL), with levels on proestrus 6 Pm reaching only two-thirds of this value (31 \u00b1 5\u2005pg\/mL). We also observed a proestrus peak in prolactin concentrations (132.5 \u00b1 17\u2005ng\/mL) that occurred earlier than expected at 2 Am. Estrone and androstenedione levels were often close to the limit of detection (LOD) and showed no consistent changes across the estrous cycle. Testosterone levels were rarely above the LOD (0.01\u2005ng\/mL). These observations provide the first detailed assessment of fluctuating gonadal steroid and reproductive hormone levels across the mouse estrous cycle and indicate that species differences exist between mice and other spontaneously ovulating species.<\/jats:p>","DOI":"10.1210\/endocr\/bqad070","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T09:23:31Z","timestamp":1683797011000},"source":"Crossref","is-referenced-by-count":60,"title":["Unexpected Plasma Gonadal Steroid and Prolactin Levels Across the Mouse Estrous Cycle"],"prefix":"10.1210","volume":"164","author":[{"given":"Ellen G","family":"Wall","sequence":"first","affiliation":[{"name":"Department of Physiology, Development, and Neuroscience, University of Cambridge , Cambridge CB2 3EG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Desai","sequence":"additional","affiliation":[{"name":"ANZAC Research Institute, University of Sydney , Sydney, NSW 2139 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zin","family":"Khant Aung","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology, University of Otago School of Biomedical Sciences , Dunedin 9014 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shel Hwa","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development, and Neuroscience, University of Cambridge , Cambridge CB2 3EG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5606-2559","authenticated-orcid":false,"given":"David R","family":"Grattan","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology, University of Otago School of Biomedical Sciences , Dunedin 9014 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Handelsman","sequence":"additional","affiliation":[{"name":"ANZAC Research Institute, University of Sydney , Sydney, NSW 2139 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9615-3022","authenticated-orcid":false,"given":"Allan E","family":"Herbison","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development, and Neuroscience, University of Cambridge , Cambridge CB2 3EG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"issue":"6","key":"2023052907492055500_bqad070-B1","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1210\/endo.142.6.8221","article-title":"Perspective: nonreproductive sites of action of reproductive hormones","volume":"142","author":"Manolagas","year":"2001","journal-title":"Endocrinology"},{"issue":"1","key":"2023052907492055500_bqad070-B2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41746-019-0152-7","article-title":"Real-world menstrual cycle characteristics of more than 600,000 menstrual cycles","volume":"2","author":"Bull","year":"2019","journal-title":"NPJ Digit Med"},{"issue":"3","key":"2023052907492055500_bqad070-B3","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/aja.1000300303","article-title":"The oestrus cycle in the mouse","volume":"30","author":"Allen","year":"1922","journal-title":"Am J Anat"},{"issue":"6","key":"2023052907492055500_bqad070-B4","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1210\/endo-94-6-1704","article-title":"Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17beta throughout the 4-day estrous cycle of the rat","volume":"94","author":"Butcher","year":"1974","journal-title":"Endocrinology"},{"issue":"1","key":"2023052907492055500_bqad070-B5","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1210\/endo-96-1-219","article-title":"The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy","volume":"96","author":"Smith","year":"1975","journal-title":"Endocrinology"},{"issue":"12","key":"2023052907492055500_bqad070-B6","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1210\/jc.2014-3424","article-title":"Editorial: the new instructions to authors for the reporting of steroid hormone measurements","volume":"99","author":"Wierman","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2023052907492055500_bqad070-B7","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1210\/jc.2013-3375","article-title":"Requirement for mass spectrometry sex steroid assays in the journal of clinical endocrinology and metabolism","volume":"98","author":"Handelsman","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2023052907492055500_bqad070-B8","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1210\/en.2014-7534","article-title":"Steroid assays and endocrinology: best practices for basic scientists","volume":"155","author":"Auchus","year":"2014","journal-title":"Endocrinology"},{"issue":"2","key":"2023052907492055500_bqad070-B9","doi-asserted-by":"crossref","first-page":"D1","DOI":"10.1530\/EJE-15-0338","article-title":"Mass spectrometry and immunoassay: how to measure steroid hormones today and tomorrow","volume":"173","author":"Taylor","year":"2015","journal-title":"Eur J Endocrinol"},{"issue":"8","key":"2023052907492055500_bqad070-B10","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1210\/en.2014-1196","article-title":"Characterization of reproductive, metabolic, and endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models","volume":"155","author":"Caldwell","year":"2014","journal-title":"Endocrinology"},{"issue":"3-5","key":"2023052907492055500_bqad070-B11","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.jsbmb.2010.02.001","article-title":"Measurement of sex steroids in murine blood and reproductive tissues by liquid chromatography-tandem mass spectrometry","volume":"121","author":"McNamara","year":"2010","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"9","key":"2023052907492055500_bqad070-B12","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1210\/en.2004-1616","article-title":"17\u03b1-Estradiol: a brain-active estrogen?","volume":"146","author":"Toran-Allerand","year":"2005","journal-title":"Endocrinology"},{"issue":"7","key":"2023052907492055500_bqad070-B13","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1210\/en.2014-1890","article-title":"Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry","volume":"156","author":"Nilsson","year":"2015","journal-title":"Endocrinology"},{"issue":"1","key":"2023052907492055500_bqad070-B14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40738-020-00074-3","article-title":"Staging of the estrous cycle and induction of estrus in experimental rodents: an update","volume":"6","author":"Ajayi","year":"2020","journal-title":"Fertil Res Pract"},{"issue":"12","key":"2023052907492055500_bqad070-B15","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.1210\/en.2016-1351","article-title":"Pulse and surge profiles of luteinizing hormone secretion in the mouse","volume":"157","author":"Czieselsky","year":"2016","journal-title":"Endocrinology"},{"issue":"9","key":"2023052907492055500_bqad070-B16","doi-asserted-by":"crossref","DOI":"10.1210\/jendso\/bvaa086","article-title":"Ultrasensitive serum estradiol measurement by liquid chromatography-mass spectrometry in postmenopausal women and mice","volume":"4","author":"Handelsman","year":"2020","journal-title":"J Endocr Soc"},{"issue":"5","key":"2023052907492055500_bqad070-B17","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1530\/REP-06-0302","article-title":"Circulating hormones and estrous stage predict cellular and stromal remodeling in murine uterus","volume":"133","author":"Wood","year":"2007","journal-title":"Reproduction"},{"key":"2023052907492055500_bqad070-B18","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jsbmb.2018.09.010","article-title":"Estrogen and progesterone dependent expression of visfatin\/NAMPT regulates proliferation and apoptosis in mice uterus during estrous cycle","volume":"185","author":"Annie","year":"2019","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"12","key":"2023052907492055500_bqad070-B19","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1210\/en.2013-1502","article-title":"Development of a methodology for and assessment of pulsatile luteinizing hormone secretion in juvenile and adult male mice","volume":"154","author":"Steyn","year":"2013","journal-title":"Endocrinology"},{"issue":"5","key":"2023052907492055500_bqad070-B20","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1210\/en.2014-1571","article-title":"Assessment of lactotroph axis functionality in mice: longitudinal monitoring of PRL secretion by ultrasensitive-ELISA","volume":"156","author":"Guillou","year":"2015","journal-title":"Endocrinology"},{"issue":"6","key":"2023052907492055500_bqad070-B21","doi-asserted-by":"crossref","DOI":"10.1111\/jne.13129","article-title":"Elevated prolactin secretion during proestrus in mice: absence of a defined surge","volume":"34","author":"Phillipps","year":"2022","journal-title":"J Neuroendocrinol"},{"issue":"10","key":"2023052907492055500_bqad070-B22","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1210\/en.2019-00340","article-title":"An accurate substitution method to minimize left censoring bias in Serum steroid measurements","volume":"160","author":"Handelsman","year":"2019","journal-title":"Endocrinology"},{"key":"2023052907492055500_bqad070-B23","volume-title":"Essential Reproduction","author":"Johnson","year":"2007","edition":"6th ed"},{"issue":"14","key":"2023052907492055500_bqad070-B24","doi-asserted-by":"crossref","first-page":"7180","DOI":"10.1021\/acs.analchem.5b01042","article-title":"Measurement of estradiol in human serum by LC-MS\/MS using a novel estrogen-specific derivatization reagent","volume":"87","author":"Keski-Rahkonen","year":"2015","journal-title":"Anal Chem"},{"issue":"3","key":"2023052907492055500_bqad070-B25","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1210\/endo.131.3.1505477","article-title":"Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: correlation with circulating estradiol and progesterone","volume":"131","author":"Walmer","year":"1992","journal-title":"Endocrinology"},{"issue":"5","key":"2023052907492055500_bqad070-B26","doi-asserted-by":"crossref","DOI":"10.1111\/jne.13094","article-title":"Neuroendocrine control of gonadotropin-releasing hormone: pulsatile and surge modes of secretion","volume":"34","author":"Goodman","year":"2022","journal-title":"J Neuroendocrinol"},{"key":"2023052907492055500_bqad070-B27","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2022.953252","article-title":"Neuroendocrine mechanisms underlying estrogen positive feedback and the LH surge","volume":"16","author":"Kauffman","year":"2022","journal-title":"Front Neurosci"},{"issue":"2","key":"2023052907492055500_bqad070-B28","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.neuron.2006.07.023","article-title":"Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility","volume":"52","author":"Wintermantel","year":"2006","journal-title":"Neuron"},{"issue":"19","key":"2023052907492055500_bqad070-B29","doi-asserted-by":"crossref","first-page":"8173","DOI":"10.1073\/pnas.0611514104","article-title":"Nonclassical estrogen receptor alpha signaling mediates negative feedback in the female mouse reproductive axis","volume":"104","author":"Glidewell-Kenney","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"2023052907492055500_bqad070-B30","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.1210\/endo.138.12.5558","article-title":"Estradiol requirements for induction and maintenance of the gonadotropin-releasing hormone surge: implications for neuroendocrine processing of the estradiol signal","volume":"138","author":"Evans","year":"1997","journal-title":"Endocrinology"},{"issue":"1","key":"2023052907492055500_bqad070-B31","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1210\/endo-96-1-50","article-title":"Role of estrogen as initiator of daily LH surges in the ovariectomized rat","volume":"96","author":"Legan","year":"1975","journal-title":"Endocrinology"},{"issue":"2","key":"2023052907492055500_bqad070-B32","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1210\/endo-108-2-506","article-title":"The regulation of luteinizing hormone secretion by estrogen: relationships among negative feedback, surge potential, and male stimulation in juvenile, peripubertal, and adult female mice","volume":"108","author":"Bronson","year":"1981","journal-title":"Endocrinology"},{"issue":"5","key":"2023052907492055500_bqad070-B33","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1210\/endo-104-5-1247","article-title":"Control of the preovulatory release of luteinizing hormone by steroids in the mouse","volume":"104","author":"Bronson","year":"1979","journal-title":"Endocrinology"},{"issue":"4346","key":"2023052907492055500_bqad070-B34","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1126\/science.418505","article-title":"Potent antidopaminergic activity of estradiol at the pituitary level on prolactin release","volume":"200","author":"Raymond","year":"1978","journal-title":"Science"},{"issue":"4","key":"2023052907492055500_bqad070-B35","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1210\/endo-106-4-1087","article-title":"Loss of estrogen-induced daily surges of prolactin and gonadotropins by suprachiasmatic nucleus lesions in ovariectomized rats","volume":"106","author":"Kawakami","year":"1980","journal-title":"Endocrinology"},{"issue":"1","key":"2023052907492055500_bqad070-B36","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1210\/endo-117-1-382","article-title":"Central nervous system regions involved in the estrogen-induced afternoon prolactin surge. I. Lesion studies","volume":"117","author":"Pan","year":"1985","journal-title":"Endocrinology"},{"issue":"3","key":"2023052907492055500_bqad070-B37","doi-asserted-by":"crossref","first-page":"126","DOI":"10.7150\/ijbs.4.126","article-title":"Sex hormones\u2019 regulation of rodent physical activity: a review","volume":"4","author":"Lightfoot","year":"2008","journal-title":"Int J Biol Sci"},{"key":"2023052907492055500_bqad070-B38","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.physbeh.2018.05.002","article-title":"Energy homeostasis and running wheel activity during pregnancy in the mouse","volume":"194","author":"Ladyman","year":"2018","journal-title":"Physiol Behav"},{"issue":"1","key":"2023052907492055500_bqad070-B39","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1677\/joe.0.1120015","article-title":"Diurnal progesterone rhythms in the female mouse","volume":"112","author":"Bailey","year":"1987","journal-title":"J Endocrinol"},{"issue":"2","key":"2023052907492055500_bqad070-B40","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.fertnstert.2020.06.016","article-title":"Luteinizing hormone-independent rise of progesterone as the physiological trigger of the ovulatory gonadotropins surge in the human","volume":"114","author":"Dozortsev","year":"2020","journal-title":"Fertil Steril"},{"issue":"6","key":"2023052907492055500_bqad070-B41","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1095\/biolreprod59.6.1296","article-title":"Mouse oocytes regulate granulosa cell steroidogenesis throughout follicular development","volume":"59","author":"Vanderhyden","year":"1998","journal-title":"Biol Reprod"},{"issue":"6","key":"2023052907492055500_bqad070-B42","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1210\/endo-118-6-2402","article-title":"Progesterone secretion by granulosa cells from rats with four- or five-day estrous cycles: the development of responses to follicle-stimulating hormone, luteinizing hormone, and testosterone","volume":"118","author":"Quirk","year":"1986","journal-title":"Endocrinology"},{"issue":"5","key":"2023052907492055500_bqad070-B43","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1210\/endo-90-5-1356","article-title":"Acute effect of gonadotrophins on the secretion of progestins by the rat ovary","volume":"90","author":"Ichikawa","year":"1972","journal-title":"Endocrinology"},{"key":"2023052907492055500_bqad070-B44","doi-asserted-by":"crossref","first-page":"832","DOI":"10.3389\/fendo.2019.00832","article-title":"Perturbations in lineage specification of Granulosa and theca cells may alter corpus luteum formation and function","volume":"10","author":"Abedel-Majed","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2023052907492055500_bqad070-B45","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/B978-0-12-397175-3.00023-5","volume-title":"Knobil and Neill's Physiology of Reproduction. Vol. 1","author":"Stouffer","year":"2015"},{"issue":"1","key":"2023052907492055500_bqad070-B46","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.cardiores.2004.09.012","article-title":"Sex and strain differences in adult mouse cardiac repolarization: importance of androgens","volume":"65","author":"Brouillette","year":"2005","journal-title":"Cardiovasc Res"},{"issue":"12","key":"2023052907492055500_bqad070-B47","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/0024-3205(92)90204-3","article-title":"Adrenal glands of mouse and rat do not synthesize androgens","volume":"50","author":"van Weerden","year":"1992","journal-title":"Life Sci"},{"issue":"1","key":"2023052907492055500_bqad070-B48","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1749-6632.2011.06325.x","article-title":"The blessings and curses of C57BL\/6 substrains in mouse genetic studies","volume":"1245","author":"Bryant","year":"2011","journal-title":"Ann N Y Acad Sci"},{"issue":"5","key":"2023052907492055500_bqad070-B49","first-page":"595","article-title":"Reproductive performance in C57BL and I strain mice","volume":"38","author":"Hoover-Plow","year":"1988","journal-title":"Lab Anim Sci"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/endocr\/bqad070\/50275233\/bqad070.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/164\/6\/bqad070\/50461540\/bqad070.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/164\/6\/bqad070\/50461540\/bqad070.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T17:46:05Z","timestamp":1702403165000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/doi\/10.1210\/endocr\/bqad070\/7159815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,17]]},"references-count":49,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,4,17]]}},"URL":"https:\/\/doi.org\/10.1210\/endocr\/bqad070","relation":{},"ISSN":["1945-7170"],"issn-type":[{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,6]]},"published":{"date-parts":[[2023,4,17]]},"article-number":"bqad070"}}