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

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41 Scopus citations


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
Article numbere0159534
JournalPLoS ONE
Issue number7
StatePublished - Jul 2016

Bibliographical note

Publisher Copyright:
© 2016 Gal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ASJC Scopus subject areas

  • General


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