Mechanisms of dihydrotestosterone action on resveratrol-induced anti-proliferation in breast cancer cells with different ERα status
ER-Alpha is the receptor through which Estrogen does most of its damage and tumor growth promotion, whereas ER-Beta has anti-proliferative properties and is activated by some phytoestrogens that have been shown to inhibit cancer growth and which consumption has been linked to lower cancer risks in epidemiological studies. This could explain why DHT may cause hair loss; while DHT is famed to be a non-aromatizable androgen this study shows that it directly triggers the most damageful estrogen receptor.
In the same study we see that DHT reduces p53, an apoptotic gene which is muted in most cancers. For instance, estrogen and iron also inhibit p53. p53 induces igfbp3 which is low in male baldness pattern sufferers.
I've also posted a study some times ago which shows that DHT is triggered by stress, and while it has some protective functions against stress it doesn't make sense that low-stress males who have lower DHT than highly stressed males are missing on health benefits. Stress is estrogenic and pro-cancer by triggering cortisol, estrogen and DHT.
Dihydrotestosterone (DHT) has been shown to promote breast cancer growth via different mechanisms. In addition to binding to ERα, the DHT membrane receptor exists on integrin αvβ3. Resveratrol induces p53-dependent apoptosis via plasma membrane integrin αvβ3. Resveratrol and DHT signals are both transduced by activated ERK1/2; however, DHT promotes cell proliferation in cancer cells, whereas resveratrol is pro-apoptotic. In this study, we examined the mechanism by which DHT inhibits resveratrol-induced apoptosis in human ERα positive (MCF-7) and negative (MDA-MB-231) breast cancer cells. DHT inhibited resveratrol-stimulated phosphorylation of Ser-15 of p53 in a concentration-dependent manner. These effects of DHT on resveratrol action were blocked by an ERα antagonist, ICI 182,780, in MCF-7 breast cancer cells.
ER-Alpha is the receptor through which Estrogen does most of its damage and tumor growth promotion, whereas ER-Beta has anti-proliferative properties and is activated by some phytoestrogens that have been shown to inhibit cancer growth and which consumption has been linked to lower cancer risks in epidemiological studies. This could explain why DHT may cause hair loss; while DHT is famed to be a non-aromatizable androgen this study shows that it directly triggers the most damageful estrogen receptor.
In the same study we see that DHT reduces p53, an apoptotic gene which is muted in most cancers. For instance, estrogen and iron also inhibit p53. p53 induces igfbp3 which is low in male baldness pattern sufferers.
I've also posted a study some times ago which shows that DHT is triggered by stress, and while it has some protective functions against stress it doesn't make sense that low-stress males who have lower DHT than highly stressed males are missing on health benefits. Stress is estrogenic and pro-cancer by triggering cortisol, estrogen and DHT.