This quite the interesting molecule, apparently not working predominantly via mTOR (although it does signal), but major liver gene expression.
“In alignment with our previous reports, 17a-E2 reduced calorie intake, body mass, adiposity, and obesity-related metabolic perturbations in male WT mice. These studies, coupled with our current findings, led us to speculate that 17a-E2 may be signaling through ERa in the liver to reverse metabolic disease and potentially extend healthspan and/or lifespan in males. We found that 17a-E2 dramatically reduced liver mass and lipid content”
I found the male/female selective responses quite profoundly interesting, especially as it relates to some further confirmations of the loss of most likely protective estrogen in post menopausal women and elevated aging chronic disease risk.
“The loss of endogenous estrogen action due to menopause in humans or ovariectomy (OVX) in rodents eliminates these beneficial effects and elicits metabolic perturbations. Moreover, OVX following sexual maturation has also been shown to reduce lifespan in female mice, indicating that endogenous estrogens regulate lifespan in females; which we surmise is at least partially mediated through ERalpha” This is pretty profound stuff if translatable to human female aging.
There’s a huge stack of smoking gun literature, especially for neurodegeneration in females associated with loss of estrogen late life.
And fundamentally, castrating male mice (blocking testosterone) completely ABLATED the effects of this molecule…wow.
“Despite these contrasting observations, the studies by Garratt et al. do provide important insights into the interconnected and under appreciated relationship between androgen- and estrogen-signaling pathways and their roles in metabolism and aging.”
“Notably, it is plausible that 17a-E2 could be inducing metabolic benefits and lifespan-extending effects through several distinct mechanisms, including direct actions through ERa, suppression of DHT production, and/or aromatization of testosterone”
https://www.sciencedirect.com/topics/medicine-and-dentistry/17alpha-estradiol
“17-α Estradiol is a weak estrogen and a potent 5-α reductase inhibitor” Another fascinating connection.