Genomic Mechanism For Beneficial Effects Of Progesterone On Pregnancy / Cancer

haidut

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Apparently, the gene Gata2 is crucial for the protective effects of progesterone against estrogen carcinogenicity, as well as for ability to enable pregnancy formation.
GATA2 - Wikipedia

This study found that progesterone acts as a Gata2 agonist and absence of the gene makes mice infertile as well as guaranteeing uterine cancer development. Apparently Gata2 agonism is functionally antagonistic to estrogen, so other Gata2 agonists should also have protective effects against estrogen as well as beneficial effects on fertility.
Mouse Gata2 gene can affect female fertility and uterine susceptibility to cancer

"...Understanding what affects the uterus’ ability to prepare for pregnancy might someday help prevent or treat female infertility and cancer. In a study published in Cell Reports, researchers at Baylor College of Medicine, the National Institute of Environmental Health Sciences, the University of California at San Francisco, Michigan State University and the University of Michigan report that in mice the gene Gata2 is essential for embryo implantation and also may protect the uterus from the cancer-causing actions of estrogen."

"...One of these steps is embryo implantation in the uterus. If the uterus is not prepared to receive the embryo, the result is infertility. Progesterone is a hormone that stimulates the uterus to support embryo implantation, and in this study the researchers discovered that the gene Gata2 can affect the uterus’ ability to respond to progesterone. “We genetically engineered mice to lack Gata2 in the uterus,” said senior author Dr. Francesco DeMayo, adjunct professor of molecular and cellular biology and pediatrics at Baylor. “The result was that the mice were infertile; their uteri were not able to respond to progesterone.”

"...In addition, the researchers discovered that Gata2 can protect the uterus from the cancer-causing effects of estrogen, a female hormone that normally promotes the development and maintenance of female characteristics. When the uterine epithelium changes from having a simple structure to a layered or stratified one, estrogen can trigger a process that may lead to cancer. “By preventing the transformation of the uterine epithelium from a simple to a layered structure, Gata2 may protect the uterus from the cancer-causing effects of estrogen,” said DeMayo.” These results are relevant to human female fertility. DeMayo and colleagues used bioinformatics analysis to show that the biochemical pathways regulated by Gata2 in the mouse also are present in the human uterus."
 

Lucha

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Thank you very much. It is very interesting as always; but this time very sad, espesially for people from "triple negative" families. So, bye bye Kansas and progest-E for girls with lack of Gata2?
 

haidut

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Thank you very much. It is very interesting as always; but this time very sad, espesially for people from "triple negative" families. So, bye bye Kansas and progest-E for girls with lack of Gata2?

Even triple negative breast cancer can respond to progesterone since the steroid has the so-called "non-genomic" (read: metabolic) beneficial effects. Genes are not required for something to have an effect, they are just one piece of the puzzle. For instance, aspirin, which protects from all known types of cancer, has no gene or receptor discovered for its mechanisms and yet it works remarkably well. So, the metabolic effects are likely much more important than the genomic ones.
 
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