Abstract
The molecular mechanisms controlling the onset of copious milk secretion are only now beginning to be elucidated. We have known for nearly four decades that progesterone suppresses milk secretion during pregnancy, and that the fall in progesterone near parturition is necessary for secretory activation. Similarly, we’ve known for 15 years that transforming growth factor β (TGFβ) also suppresses milk secretion. Yet no formal link between the two has ever been established. This work aims to review the evidence for and against a link between progesterone and TGFβ, raise unanswered questions, and to propose further lines of research.
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Abbreviations
- TGFβ:
-
transforming growth factor beta
- BMP:
-
bone morphogenic protein
- MMP:
-
matrix metalloproteinase
- TIMP:
-
tissue-inhibitor of metalloproteinase
- LAP:
-
latency-associated peptide
- Smad:
-
Mad-homolog
- TβRI:
-
type I TGFβ receptor
- TβRII:
-
type II TGFβ receptor
- PR:
-
progesterone receptor
- ER:
-
estrogen receptor
- AR:
-
androgen receptor
- IGF:
-
insulin-like growth factor
- MEC:
-
mammary epithelial cell
- SBE:
-
Smad-binding element
- EMT:
-
epithelial to mesenchymal transition
- MET:
-
mesenchymal to epithelial transition
- MAPK:
-
mitogen-activated kinase
- P4:
-
progesterone,
- JNK:
-
the c-Jun NH2 terminal kinase
- PI3K:
-
phosphatidylinositol kinase
- TAK1:
-
TGFβ-activated kinase
- PP2A:
-
protein phosphatase 2A
- Par6:
-
partitioning-defective protein 6
- DAXX:
-
death-associated protein 6
- IGFBP:
-
insulin-like growth factor binding protein
- LRP:
-
low-density lipoprotein-related receptor
- WAP:
-
whey acidic protein
- VDR:
-
vitamin D receptor
- PMEC:
-
primary mammary epithelial cells
- SGAGs:
-
sulfated glycosaminoglycans
- AP2B1:
-
adaptor-related protein complex 2, beta 1 subunit
- FKBP1A:
-
FK506 binding protein 1A (12 kDa)
- STRAP:
-
serine–threonine–kinase receptor-associated protein
- ZAK:
-
sterile alpha motif and leucine zipper containing kinase AZK
- SMURF2:
-
Smad specific E3 ubiquitin ligase 2
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Acknowledgments
Owing to space limitations, only selected works from the literature have been cited. Sincere apologies to those colleagues with relevant publications that were missed. This work was supported by NIH PO1-HD38129, Margaret C. Neville, PI.
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This work was supported by NIH PO1-HD38129, Margaret C. Neville, PI.
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Monks, J. TGFβ as a Potential Mediator of Progesterone Action in the Mammary Gland of Pregnancy. J Mammary Gland Biol Neoplasia 12, 249–257 (2007). https://doi.org/10.1007/s10911-007-9056-2
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DOI: https://doi.org/10.1007/s10911-007-9056-2