title: Signaling role of prokineticin 2 on the estrous cycle of female mice.
abstract: The possible signaling role of prokineticin 2 (PK2) and its receptor, prokineticin receptor 2 (PKR2), on female reproduction was investigated. First, the expression of PKR2 and its co-localization with estrogen receptor (ERα) in the hypothalamus was examined. Sexually dimorphic expression of PKR2 in the preoptic area of the hypothalamus was observed. Compared to the male mice, there was more widespread PKR2 expression in the preoptic area of the hypothalamus in the female mice. The likely co-expression of PKR2 and ERα in the preoptic area of the hypothalamus was observed. The estrous cycles in female PK2-null, and PKR2-null heterozygous mice, as well as in PK2-null and PKR2-null compound heterozygous mice were examined. Loss of one copy of PK2 or PKR2 gene caused elongated and irregular estrous cycle in the female mice. The alterations in the estrous cycle were more pronounced in PK2-null and PKR2-null compound heterozygous mice. Consistent with these observations, administration of a small molecule PK2 receptor antagonist led to temporary blocking of estrous cycle at the proestrous phase in female mice. The administration of PKR2 antagonist was found to blunt the circulating LH levels. Taken together, these studies indicate PK2 signaling is required for the maintenance of normal female estrous cycles.
authors.affiliation: Department of Pharmacology, University of California, Irvine, California, United States of America; Department of Endocrinology, Jinshan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, University of California, Irvine, California, United States of America.
authors.forename: Chengkang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, University of California, Irvine, California, United States of America.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Li
authors.affiliation: GENSAT Project, The Rockefeller University, New York, New York, United States of America.
authors.forename: Shiaoching
authors.initials: S
authors.lastname: Gong
authors.affiliation: Institute of Endocrinology and Diabetology, Huashan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Renming
authors.initials: R
authors.lastname: Hu
authors.affiliation: Harvard Reproductive Endocrine Sciences Center & The Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Balasubramanian
authors.affiliation: Harvard Reproductive Endocrine Sciences Center & The Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: William F
authors.initials: WF
authors.lastname: Crowley W
authors.affiliation: Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hastings
authors.affiliation: Department of Pharmacology, University of California, Irvine, California, United States of America.
authors.forename: Qun-Yong
authors.initials: QY
authors.lastname: Zhou
mesh_terms: D000818:Animals; D047628:Estrogen Receptor alpha / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005768:Gastrointestinal Hormones / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C486586:Prok2 protein, mouse