Estrogen receptors are docking proteins that let estrogen act inside muscle and blood vessel cells. eNOS is the enzyme that makes nitric oxide, which relaxes and widens vessels, while NOX2 generates reactive oxygen species that push the other way. Measuring them together shows which side of that balance the muscle is sitting on.
Drawn from the paper's introduction.
The authors note it has been hypothesised that age related declines in skeletal muscle and vascular function in women may be partly estrogen dependent, but that human studies of estrogen receptor expression in muscle are very limited.
So they set out to map receptor expression against age, menopausal status and lifelong physical activity, and to see how it relates to proteins involved in redox regulation and vascular function.
Hypothesis They hypothesised that estrogen receptor alpha and GPER1 expression would decline with aging while estrogen receptor beta would increase, with these changes associated with impaired redox balance in older females.
Drawn from the paper's introduction.
Skeletal muscle biopsies were taken from 107 healthy women aged 19 to 70, including a subgroup of 26 postmenopausal women who had trained throughout their lives. The team quantified protein expression of estrogen receptor alpha, estrogen receptor beta and the G protein coupled estrogen receptor GPER1, alongside downstream proteins involved in redox regulation and vascular function.
Estrogen receptor alpha was 48 percent lower in women aged 55 and over than in those under 30. GPER1 was 22 percent lower across all older age groups. Estrogen receptor beta was reduced in mid life, between 45 and 59, but not in the oldest group. Both estrogen receptor alpha and beta correlated positively with endothelial nitric oxide synthase, the enzyme that makes the nitric oxide which relaxes blood vessels. GPER1 showed no such association.
Estrogen receptor beta was associated with NOX2, a pro-oxidant enzyme, which is the observation the authors build their interpretation on. The hypothesis going in had been that receptor alpha and GPER1 would fall with age while receptor beta would rise. The first part held and the second did not, since receptor beta fell in mid life and recovered in the oldest group.
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Proposed by the authors This is the explanation the authors offer in their discussion. This study did not test it.
The authors propose that aging shifts the balance between the two main estrogen receptors toward a more pro-oxidative muscle environment.
Their evidence for that is associational and within this dataset: receptor alpha tracked with antioxidant enzymes and with the nitric oxide producing enzyme, while receptor beta tracked with the pro-oxidant NOX2, which suggests the two receptors sit on different sides of redox regulation.
Drawn from the paper's discussion.
It supports, with human data, an idea that had rested largely on animal work: that estrogen signalling in skeletal muscle declines with age in women and moves together with the proteins governing nitric oxide and oxidative balance.
Healthy women aged 19 to 70, with an older subgroup who had trained throughout their lives.
A study that adds functional oxidative stress and muscle function outcomes, and measures receptor activity rather than receptor abundance, which the authors themselves flag as the gap.
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