phytoesterogens Flashcards
phytoestrogens
plant derived compounds, mimic estrogen at specific sites in the body
phytoestrogen in bones
decrease bone resorption and delay osteoporosis progression
aglycones
phytoestrogen after removal of sugar group, active form
cleaved after ingestion
estrogen receptors
ERa and ERB
facilitate actions at the level of DNA transcription and signaling cascades
ERa: uterus, vagina, ovaries, mammary gland, hypothalamus
ERB: prostate and ovaries, lungs brain bones
bind phytoestrogens
estradiol (E2)
natural estrogen
phenolic A ring responsible for selective high-affinity binding to ER
phytoestrogens have lower affinity but higher concentration than natural estrogen
shown to promote vascular relaxation
vasodilators
NO, prostaglandin I2 (PGI2)
vasoconstrictors
angiotensin II, endothelin (ET)
phytoestrogen and Ca+ mechanism
phytoestrogens stimulate NO, which triggers the removal of Ca2+ in VSM cells through pumps > muscle relaxation and vasodilation
also through PGI2-cAMP-PKA pathway > removal of Ca2+
mechanisms in which phytoestrogens affect vascular smooth muscle (also applies to epicatechin)
1) Ca2+/calmodulin pathway
2) PI3K/AKT pathway
Both activate eNOS
phytoestrogens have shown to inhibit osteoclastogenesis
inhibit bone resorption
ET-1
causes Ca2+ influx into VSM, vasoconstriction
inhibited by phytoestrogens
osteoblast vs osteoclasts
bone forming vs bone resorbing (break down bone tissue)
RANKL
produced in osteoblasts, binds to osteoclasts
induces osteoclastogenesis
activates MAPK, AKT, NFkB downstream
BMPs (Bone morphogenetic proteins)
critical in osteogenesis
stimulates transcription factors Runx2 and Smads (facilitates differentiation to osteoblasts)
BMP-activated MAPKs and Smads control MSCs differentiation through Runx2
how do osteoclasts develop??
RANKL > MAPKs > NFkB activation > osteoclasts development and proliferation