Loss of Fertility in the Absence of Progesterone Receptor Expression in Kisspeptin Neurons of Female Mice

Arnon Gal, Po Ching Lin, Joseph A. Cacioppo, Patrick R. Hannon, Megan M. Mahoney, Andrew Wolfe, Rodrigo Fernandez-Valdivia, John P. Lydon, Carol F. Elias, Che Myong Ko

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0159534
JournalPloS one
Volume11
Issue number7
DOIs
StatePublished - Jul 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Gal, A., Lin, P. C., Cacioppo, J. A., Hannon, P. R., Mahoney, M. M., Wolfe, A., Fernandez-Valdivia, R., Lydon, J. P., Elias, C. F., & Ko, C. M. (2016). Loss of Fertility in the Absence of Progesterone Receptor Expression in Kisspeptin Neurons of Female Mice. PloS one, 11(7), [e0159534]. https://doi.org/10.1371/journal.pone.0159534