{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:30:27Z","timestamp":1790350227965,"version":"4.1.0"},"reference-count":71,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pituitary is an organ of dual provenance: the anterior lobe is epithelial in origin, whereas the posterior lobe derives from the neural ectoderm. The pituitary gland is a pivotal element of the axis regulating reproductive function in mammals. It collects signals from the hypothalamus, and by secreting gonadotropins (FSH and LH) it stimulates the ovary into cyclic activity resulting in a menstrual cycle and in ovulation. Pituitary organogenesis is comprised of three main stages controlled by different signaling molecules: first, the initiation of pituitary organogenesis and subsequent formation of Rathke\u2019s pouch; second, the migration of Rathke\u2019s pouch cells and their proliferation; and third, lineage determination and cellular differentiation. Any disruption of this sequence, e.g., gene mutation, can lead to numerous developmental disorders. Gene mutations contributing to disordered pituitary development can themselves be classified: mutations affecting transcriptional determinants of pituitary development, mutations related to gonadotropin deficiency, mutations concerning the beta subunit of FSH and LH, and mutations in the DAX-1 gene as a cause of adrenal hypoplasia and disturbed responsiveness of the pituitary to GnRH. All these mutations lead to disruption in the hypothalamic\u2013pituitary\u2013ovarian axis and contribute to the development of primary amenorrhea.<\/jats:p>","DOI":"10.3390\/ijms222413241","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T23:30:00Z","timestamp":1639006200000},"page":"13241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Genetic Backdrop of Hypogonadotropic Hypogonadism"],"prefix":"10.3390","volume":"22","author":[{"given":"Anna","family":"Szeliga","sequence":"first","affiliation":[{"name":"Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Kunicki","sequence":"additional","affiliation":[{"name":"INVICTA Fertility and Reproductive Center, 00-019 Warsaw, Poland"},{"name":"Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"Maciejewska-Jeske","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9228-3014","authenticated-orcid":false,"given":"Natalia","family":"Rzewuska","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kostrzak","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blazej","family":"Meczekalski","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Bala","sequence":"additional","affiliation":[{"name":"Appletree Medical Group, Ottawa, ON K1R 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-5433","authenticated-orcid":false,"given":"Roman","family":"Smolarczyk","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli Y.","family":"Adashi","sequence":"additional","affiliation":[{"name":"Warren Alpert Medical School, Brown University, 272 George St., Providence, RI 02906, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"key":"ref_1","unstructured":"Larkin, S., and Ansorge, O. 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