Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

Abstract:

:Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.

journal_name

Genes Dev

journal_title

Genes & development

authors

Lydon JP,DeMayo FJ,Funk CR,Mani SK,Hughes AR,Montgomery CA Jr,Shyamala G,Conneely OM,O'Malley BW

doi

10.1101/gad.9.18.2266

subject

Has Abstract

pub_date

1995-09-15 00:00:00

pages

2266-78

issue

18

eissn

0890-9369

issn

1549-5477

journal_volume

9

pub_type

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