{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:54:49Z","timestamp":1772553289839,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,27]]},"group-title":"Neuroscience","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R01HD104345"],"award-info":[{"award-number":["R01HD104345"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["F31HD110279"],"award-info":[{"award-number":["F31HD110279"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Polycystic ovary syndrome (PCOS), a common cause of infertility, is marked by persistently high luteinizing hormone (LH)-pulse frequency, presumably driven by high-frequency GnRH pulses. Prenatally androgenized (PNA) mice mimic neuroendocrine PCOS symptoms including high LH-pulse frequency. GnRH neurons from adult PNA mice have a higher firing rate than those from vehicle (VEH) mice; this is reversed in prepubertal mice despite more excitatory inputs at both ages. We hypothesized voltage-gated Ca\n                  <jats:sup>2+<\/jats:sup>\n                  currents (I\n                  <jats:sub>Ca<\/jats:sub>\n                  ) help set intrinsic excitability of GnRH neurons and are altered by development and\/or PNA treatment. Whole-cell patch-clamp recordings were used to measure GnRH neuron I\n                  <jats:sub>Ca<\/jats:sub>\n                  in 3wk-old and adult VEH and PNA mice. PNA treatment increased I\n                  <jats:sub>Ca<\/jats:sub>\n                  density and depolarized the I\n                  <jats:sub>Ca<\/jats:sub>\n                  -half inactivation potential at both ages. In VEH but not PNA mice, the Ca\n                  <jats:sup>2+<\/jats:sup>\n                  -half activation potential was depolarized in adults versus 3wks. Age decreased the inactivation rate of a fast I\n                  <jats:sub>Ca<\/jats:sub>\n                  regardless of PNA treatment. GnRH neuron firing rate during current injections was higher at 3wks than in adulthood in VEH mice only. Blocking small-conductance Ca\u00b2\u207a-activated K\u207a current with apamin increased GnRH neuron firing rate except in adult PNA mice. Apamin changed the post-spike-train membrane response from hyperpolarization to depolarization; during development, this net effect of apamin became smaller in PNA mice. In summary, while GnRH neurons from PNA mice have increased I\n                  <jats:sub>Ca<\/jats:sub>\n                  , they lack some developmental changes in I\n                  <jats:sub>Ca<\/jats:sub>\n                  kinetics and intrinsic excitability observed in VEH mice. Ca\u00b2\u207a-activated K\u207a currents are less prominent in GnRH neurons from adult PNA mice, perhaps contributing to increased spontaneous firing.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance statement<\/jats:title>\n                  <jats:p>\n                    Hyperactivation of GnRH neurons, which control reproductive endocrine function, can lead to increased LH-pulse frequency and is a hallmark of hyperandrogenemia polycystic ovary syndrome (PCOS). We used a mouse model of prenatal androgenization (PNA) that recapitulates the neuroendocrine aspects of PCOS to test the role of calcium currents (I\n                    <jats:sub>Ca<\/jats:sub>\n                    ) in the PNA phenotype and the typical pubertal process. PNA treatment increased I\n                    <jats:sub>Ca<\/jats:sub>\n                    in GnRH neurons both before and after puberty. Calcium plays a crucial role in neurosecretion thus this may enhance GnRH release. Another role of calcium is activation of calcium-sensitive potassium currents, which tend to decrease action potential firing rate. Despite increased I\n                    <jats:sub>Ca,<\/jats:sub>\n                    calcium-activated potassium currents are less effective in adult PNA mice, perhaps contributing to GnRH neuron hyperactivation.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.25.707515","type":"posted-content","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:00:19Z","timestamp":1772226019000},"source":"Crossref","is-referenced-by-count":0,"title":["\u2202Voltage-gated calcium channel activity of gonadotropin-releasing hormone (GnRH) neurons is altered by age and by prenatal androgen exposure in female mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9445-3240","authenticated-orcid":false,"given":"Xi","family":"Chen","sequence":"first","affiliation":[{"name":"Departments of Molecular & Integrative Physiology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0870-2149","authenticated-orcid":false,"given":"Jennifer","family":"Jaime","sequence":"additional","affiliation":[{"name":"The Neuroscience Graduate Program,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-7528","authenticated-orcid":false,"given":"R. Anthony","family":"DeFazio","sequence":"additional","affiliation":[{"name":"Departments of Molecular & Integrative Physiology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9812-0497","authenticated-orcid":false,"given":"Suzanne M.","family":"Moenter","sequence":"additional","affiliation":[{"name":"Departments of Molecular & Integrative Physiology,"},{"name":"Department of Internal Medicine,"},{"name":"Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA, 48109-5622"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026030304552027000_2026.02.25.707515v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6879204"},{"key":"2026030304552027000_2026.02.25.707515v1.2","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1152\/jn.1984.51.3.552","article-title":"Analysis of intracellularly recorded phasic bursting by mammalian neuroendocrine cells","volume":"51","year":"1984","journal-title":"J Neurophysiol"},{"key":"2026030304552027000_2026.02.25.707515v1.3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.79.1.119"},{"key":"2026030304552027000_2026.02.25.707515v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.100883"},{"key":"2026030304552027000_2026.02.25.707515v1.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2304-17.2018"},{"key":"2026030304552027000_2026.02.25.707515v1.6","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.70.5.549"},{"key":"2026030304552027000_2026.02.25.707515v1.7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2606"},{"key":"2026030304552027000_2026.02.25.707515v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.12.021"},{"key":"2026030304552027000_2026.02.25.707515v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2011.12.007"},{"key":"2026030304552027000_2026.02.25.707515v1.10","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a003947"},{"key":"2026030304552027000_2026.02.25.707515v1.11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2355-22.2023"},{"key":"2026030304552027000_2026.02.25.707515v1.12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-2359"},{"key":"2026030304552027000_2026.02.25.707515v1.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3171-06.2006"},{"key":"2026030304552027000_2026.02.25.707515v1.14","doi-asserted-by":"publisher","DOI":"10.1210\/endo-111-5-1737"},{"key":"2026030304552027000_2026.02.25.707515v1.15","doi-asserted-by":"publisher","DOI":"10.1210\/endo-125-2-917"},{"key":"2026030304552027000_2026.02.25.707515v1.16","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0163"},{"key":"2026030304552027000_2026.02.25.707515v1.17","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00768"},{"key":"2026030304552027000_2026.02.25.707515v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(97)81873-0"},{"key":"2026030304552027000_2026.02.25.707515v1.19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.11.4047"},{"key":"2026030304552027000_2026.02.25.707515v1.20","doi-asserted-by":"crossref","first-page":"130862","DOI":"10.1016\/j.bbagen.2025.130862","article-title":"AMPK regulates BK-channel current in CA1 hippocampal neurons","volume":"1869","year":"2025","journal-title":"Biochim Biophys Acta Gen Subj"},{"key":"2026030304552027000_2026.02.25.707515v1.21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12958-017-0282-1","article-title":"A novel method to demonstrate that pregnant women with polycystic ovary syndrome hyper-expose their fetus to androgens as a possible stepping stone for the developmental theory of PCOS. 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