title: Loss of Fertility in the Absence of Progesterone Receptor Expression in Kisspeptin Neurons of Female Mice.
abstract: Ovarian steroids, estradiol and progesterone, play central roles in regulating female reproduction by acting as both positive and negative regulators of gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus. Recent studies have identified kisspeptin neurons of the hypothalamus as the target of estrogenic regulation of GnRH secretion. In this study, we aimed to determine the significance of progesterone receptor (PGR) expression in the kisspeptin neurons. To this end, the Pgr gene was selectively ablated in mouse kisspeptin neurons and the reproductive consequence assessed. The hypothalamus of the Pgr deficient female mouse expressed kisspeptin, the pituitary released LH in response to GnRH stimulation, and the ovary ovulated when stimulated with gonadotropins. However, the mutant mouse gradually lost cyclicity, was unable to generate a LH surge in response to rising estradiol, and eventually became infertile. Taken together, these results indicate that the loss of PGR impairs kisspeptin secretory machinery and therefore that PGR plays a critical role in regulating kisspeptin secretion.
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.|Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
authors.forename: Arnon
authors.initials: A
authors.lastname: Gal
authors.affiliation: Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
authors.forename: Po-Ching
authors.initials: PC
authors.lastname: Lin
authors.affiliation: Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Cacioppo
authors.affiliation: Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hannon
authors.affiliation: Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Mahoney
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wolfe
authors.affiliation: Department of Pathology and Department of Oncology, Wayne State University School of Medicine, Detroit, MI, United States of America; Tumor Biology Microenvironment Program, Karmanos Cancer Institute, Detroit, MI, United States of America.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Fernandez-Valdivia
authors.affiliation: Center of Reproductive Medicine and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Carol F
authors.initials: CF
authors.lastname: Elias
authors.affiliation: Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
authors.forename: CheMyong
authors.identifier: http://orcid.org/0000-0002-0963-3731
authors.initials: C
authors.lastname: Ko
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D059648:Kisspeptins / Q000235:genetics* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D059648:Kisspeptins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone