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Title: Activation function 1 of progesterone receptor is required for mammary development and regulation of RANKL during pregnancy
Authors: Lee, Shi Hao
Yap, Yeannie H. Y.
Lim, Chew Leng
Woo, Amanda Rui En
Lin, Valerie Chun Ling
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Lee, S. H., Yap, Y. H. Y., Lim, C. L., Woo, A. R. E. & Lin, V. C. L. (2022). Activation function 1 of progesterone receptor is required for mammary development and regulation of RANKL during pregnancy. Scientific Reports, 12(1), 12286-.
Project: MOE-T2EP30121-0018 
Journal: Scientific Reports 
Abstract: Progesterone receptor (PGR) is a member of the nuclear receptor superfamily of transcription factors. It is critical for mammary stem cells expansion, mammary ductal branching and alveologenesis. The transcriptional activity of PGR is mainly mediated by activation functions AF1 and AF2. Although the discovery of AF1 and AF2 propelled the understanding of the mechanism of gene regulation by nuclear receptors, their physiological roles are still poorly understood. This is largely due to the lack of suitable genetic models. The present study reports gain or loss of AF1 function mutant mouse models in the study of mammary development. The gain of function mutant AF1_QQQ exhibits hyperactivity while the loss of function mutant AF1_FFF shows hypoactivity on mammary development. However, the involvement of AF1 is context dependent. Whereas the AF1_FFF mutation causes significant impairment in mammary development during pregnancy or in response to estrogen and progesterone, it has no effect on mammary development in nulliparous mice. Furthermore, Rankl, but not Wnt4 and Areg is a major target gene of AF1. In conclusion, PGR AF1 is a pivotal ligand-dependent activation domain critical for mammary development during pregnancy and it exerts gene specific effect on PGR regulated genes.
ISSN: 2045-2322
DOI: 10.1038/s41598-022-16289-x
Schools: School of Biological Sciences 
Rights: © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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