{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:33:12Z","timestamp":1761708792023},"reference-count":36,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Because pregnancy and estrogens both induce pituitary lactotroph hyperplasia, we assessed the expression of pituitary cell cycle regulators in two models of murine pituitary hyperplasia. Female mice were assessed during nonpregnancy, pregnancy, day of delivery, and postpartum. We also implanted estradiol (E2) pellets in female mice and studied them for 2.5 months. Pituitary weight in female mice increased 2-fold after E2 administration and 1.4-fold at day of delivery, compared with placebo-treated or nonpregnant females. Pituitary proliferation, as assessed by proliferating cell nuclear antigen and\/or Ki-67 staining, increased dramatically during both mid-late pregnancy and E2 administration, and lactotroph hyperplasia was also observed. Pregnancy induced pituitary cell cycle proliferative and inhibitory responses at the G1\/S checkpoint. Differential cell cycle regulator expression included cyclin-dependent kinase inhibitors, p21Cip1, p27Kip1, and cyclin D1. Pituitary cell cycle responses to E2 administration partially recapitulated those effects observed at mid-late pregnancy, coincident with elevated circulating mouse E2, including increased expression of proliferating cell nuclear antigen, Ki-67, p15INK4b, and p21Cip1. Nuclear localization of pituitary p21Cip1 was demonstrated at mid-late pregnancy but not during E2 administration, suggesting a cell cycle inhibitory role for p21Cip1 in pregnancy, yet a possible proproliferative role during E2 administration. Most observed cell cycle protein alterations were reversed postpartum. Murine pituitary meets the demand for prolactin during lactation associated with induction of both cell proliferative and inhibitory pathways, mediated, at least partially, by estradiol.<\/jats:p>","DOI":"10.1210\/en.2012-1492","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T17:45:03Z","timestamp":1348249503000},"page":"5011-5022","source":"Crossref","is-referenced-by-count":6,"title":["Estradiol Partially Recapitulates Murine Pituitary Cell Cycle Response to Pregnancy"],"prefix":"10.1210","volume":"153","author":[{"given":"Yoel","family":"Toledano","sequence":"first","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Zonis","sequence":"first","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song-Guang","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kolja","family":"Wawrowsky","sequence":"first","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Chesnokova","sequence":"first","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomo","family":"Melmed","sequence":"first","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613023656900_B1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0940-9602(03)80068-7","article-title":"Variations in the cellular proliferation of prolactin cells from late pregnancy to lactation in rats.","volume":"185","author":"Carretero","year":"2003","journal-title":"Ann Anat"},{"key":"2020071613023656900_B2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0303-7207(84)90007-8","article-title":"Regulation of pituitary DNA synthesis during different reproductive states in the female rat: role of estrogens and prolactin.","volume":"35","author":"Jahn","year":"1984","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613023656900_B3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000054574","article-title":"Differential regulation of prolactin release and lactotrope proliferation during pregnancy, lactation and the estrous cycle.","volume":"72","author":"Yin","year":"2000","journal-title":"Neuroendocrinology"},{"key":"2020071613023656900_B4","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0025-6196(12)60946-X","article-title":"The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases.","volume":"65","author":"Scheithauer","year":"1990","journal-title":"Mayo Clin Proc"},{"key":"2020071613023656900_B5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/BF02899695","article-title":"Pituitary lactotrophs and somatotrophs in pregnancy: a correlative in situ hybridization and immunocytochemical study.","volume":"62","author":"Stefaneanu","year":"1992","journal-title":"Virchows Arch B Cell Pathol Incl Mol Pathol"},{"key":"2020071613023656900_B6","first-page":"360","article-title":"Prolactin cells in the human pituitary. 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