{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:24:35Z","timestamp":1790753075444,"version":"4.1.0"},"reference-count":52,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Puberty is a tightly regulated process that leads to reproductive capacity. Kiss1 neurons are crucial in this process by stimulating GnRH, yet how Kiss1 neurons are regulated remains unknown. Substance P (SP), an important neuropeptide in pain perception, induces gonadotropin release in adult mice in a kisspeptin-dependent manner. Here, we assessed whether SP, through binding to its receptor NK1R (neurokinin 1 receptor), participates in the timing of puberty onset and fertility in the mouse. We observed that 1) selective NK1R agonists induce gonadotropin release in prepubertal females; 2) the expression of Tac1 (encoding SP) and Tacr1 (NK1R) in the arcuate nucleus is maximal before puberty, suggesting increased SP tone; 3) repeated exposure to NK1R agonists prepubertally advances puberty onset; and 4) female Tac1\u2212\/\u2212 mice display delayed puberty; moreover, 5) SP deficiency leads to subfertility in females, showing fewer corpora lutea and antral follicles and leading to decreased litter size. Thus, our findings support a role for SP in the stimulation of gonadotropins before puberty, acting via Kiss1 neurons to stimulate GnRH release, and its involvement in the attainment of full reproductive capabilities in female mice.<\/jats:p>","DOI":"10.1210\/en.2014-2012","type":"journal-article","created":{"date-parts":[[2015,4,9]],"date-time":"2015-04-09T16:29:25Z","timestamp":1428596965000},"page":"2313-2322","source":"Crossref","is-referenced-by-count":60,"title":["Substance P Regulates Puberty Onset and Fertility in the Female Mouse"],"prefix":"10.1210","volume":"156","author":[{"given":"Serap","family":"Simavli","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension (S.S., I.R.T., C.A.M., J.C.G., R.S.C., U.B.K., V.M.N.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain R.","family":"Thompson","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension (S.S., I.R.T., C.A.M., J.C.G., R.S.C., U.B.K., V.M.N.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A.","family":"Maguire","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension (S.S., I.R.T., C.A.M., J.C.G., R.S.C., U.B.K., V.M.N.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Gill","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension (S.S., I.R.T., C.A.M., J.C.G., R.S.C., U.B.K., V.M.N.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rona S.","family":"Carroll","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension (S.S., I.R.T., C.A.M., J.C.G., R.S.C., U.B.K., V.M.N.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wolfe","sequence":"first","affiliation":[{"name":"Department of Pediatrics (A.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula B.","family":"Kaiser","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension (S.S., I.R.T., C.A.M., J.C.G., R.S.C., U.B.K., V.M.N.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor M.","family":"Navarro","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension (S.S., I.R.T., C.A.M., J.C.G., R.S.C., U.B.K., V.M.N.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2016,11,14]]},"reference":[{"issue":"3","key":"2020071612082412900_B1","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1152\/physrev.00037.2010","article-title":"Kisspeptins and reproduction: physiological roles and regulatory mechanisms","volume":"92","author":"Pinilla","year":"2012","journal-title":"Physiol Rev"},{"issue":"19","key":"2020071612082412900_B2","doi-asserted-by":"crossref","first-page":"10972","DOI":"10.1073\/pnas.1834399100","article-title":"Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54","volume":"100","author":"de Roux","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"issue":"17","key":"2020071612082412900_B3","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1056\/NEJMoa035322","article-title":"The GPR54 gene as a regulator of puberty","volume":"349","author":"Seminara","year":"2003","journal-title":"N Engl J Med"},{"issue":"4","key":"2020071612082412900_B4","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.bbrc.2003.11.066","article-title":"The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system","volume":"312","author":"Funes","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"issue":"10","key":"2020071612082412900_B5","doi-asserted-by":"crossref","first-page":"4927","DOI":"10.1210\/en.2007-0078","article-title":"Kiss1\u2212\/\u2212 mice exhibit more variable hypogonadism than Gpr54\u2212\/\u2212 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