diet, hormones, aging, immune function

[jimmylegs]

Estrogen synthesis and signaling pathways during ageing: from periphery to brain (2013)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595330/

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissue as liver, heart, muscle, bone and brain. The tissue-specific estrogen synthesis is consistent with a diversity of estrogen actions. Here, we will focus on tissue and cell-specific estrogen synthesis and estrogen receptor signaling. This review will include three parts: (I) tissue and cell-specific estrogen synthesis and metabolism, (II) tissue and cell-specific distribution of estrogen receptors and signaling and (III) tissue-specific estrogen function and related disorders, including cardiovascular diseases, osteoporosis, Alzheimer's disease and Parkinson disease. This comprehensive review provides new insights into estrogens by giving a better understanding of the tissue-specific estrogen effects and their roles in various diseases.

[jimmylegs]

ok this is great. just saved me a huge whackload of time figuring out what circulating hormone levels are in different contexts. next!

Sources of estrogen and their importance (2003)
https://pubmed.ncbi.nlm.nih.gov/14623515/

Abstract
In premenopausal women, the ovaries are the principle source of estradiol, which functions as a circulating hormone to act on distal target tissues. However, in postmenopausal women when the ovaries cease to produce estrogen, and in men, this is no longer the case, because estradiol is no longer solely an endocrine factor. Instead, it is produced in a number of extragonadal sites and acts locally at these sites as a paracrine or even intracrine factor. These sites include the mesenchymal cells of adipose tissue including that of the breast, osteoblasts and chondrocytes of bone, the vascular endothelium and aortic smooth muscle cells, and numerous sites in the brain. Thus, circulating levels of estrogens in postmenopausal women and in men are not the drivers of estrogen action, they are reactive rather than proactive. This is because in these cases circulating estrogen originates in the extragonadal sites where it acts locally, and if it escapes local metabolism then it enters the circulation.

[jimmylegs]

Extra-gonadal sites of estrogen biosynthesis and function (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227141/

"...
Brain
High levels of estrogen receptors are expressed during brain development. During this period, sex hormones determine apoptosis, neuronal migration, neurogenesis, axonal guidance, and synaptogenesis. Estradiol induces sexual differentiation in the developing brain. Aromatase mRNA expression in the hypothalamus of males peaks before and after birth, inducing sexual differentiation of the brain (76). In the brains of both males and females, estradiol provides a neuroprotective effect. Estradiol’s prevention of neurodegeneration in brain tissues is proven in both the Cyp19KO mouse model and the aromatase inhibitor-treated mouse (8). Inhibition or null mutation of aromatase, a key enzyme for estradiol synthesis, results in accelerated neurodegeneration (8). Estradiol effects in the brain also include regulating mood, pain sensitivity, motor control, and cognitive behavior (13-16). Estradiol regulates neuronal metabolism by modulating the expression of metabolic enzymes such as GLUT (glucose-transporter), glycolytic enzyme hexokinase, pyruvate dehydrogenase (PDH), aconitase, and ATP synthase (77).
..."

[jimmylegs]

Aromatase Cytochrome P450 and Extragonadal Estrogen Play a Role in Ischemic Neuroprotection (2003)
https://www.jneurosci.org/content/23/25/8701

don't know exactly what that study means yet, but oh hey cytochrome p450...

[jimmylegs]

Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women (2020)
https://www.pnas.org/content/117/37/22962

"... Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. ..."

[jimmylegs]

Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke (2021)
https://bsd.biomedcentral.com/articles/ ... 20-00357-w

not sure how this one will end up factoring in...^

[jimmylegs]

Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid (2017)
https://www.nature.com/articles/s41598-017-06630-0

"Results
Dietary supplementation with DHA increases the expression of P450arom and 17β-estradiol...
Discussion
When mice were fed an n-3 polyunsaturated fatty acid-deficient diet supplemented with DHA, P450arom expression and 17β-estradiol levels in the cerebral cortex were highly elevated. Because P450arom is an enzyme that synthesizes 17β-estradiol from testosterone, the increases in 17β-estradiol are most likely due to the upregulation of P450arom...."

right on, i just restocked on high dha fish oil, 3 of those so far today, plus had a few shrimp and a little salmon this eve.
out of the high dha algae oil, though. it's on the list

[jimmylegs]

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses (2018)
https://www.frontiersin.org/articles/10 ... 00374/full

"Aromatase is the enzyme responsible for converting testosterone to estradiol. In mammals, aromatase is expressed in the testes, ovaries, brain, and other tissues. ... It is now well-recognized that aromatase plays a vital lifetime role in brain development and neurobehavioral function in both sexes. Thus, ongoing investigations seek to highlight potentially vital sex differences in the role of aromatase, particularly regarding its centrally mediated effects. ..."

Human Cognitive Ability Is Modulated by Aromatase Availability in the Brain in a Sex-Specific Manner (2020)
https://www.frontiersin.org/articles/10 ... 65668/full

[jimmylegs]

and circling back to cd20, levels of which have been shown elsewhere to decrease with estrogen therapy:

The effects of diet-induced obesity on B cell function (2014)
https://onlinelibrary.wiley.com/doi/ful ... /cei.12444

"... High fat diets promote accumulation of select murine B cell phenotypes in visceral adipose tissue. As a consequence, B cells exacerbate inflammation and thereby insulin sensitivity through the production of autoantibodies and via cross-talk with select adipose resident macrophages, CD4+ and CD8+ T cells. In contrast, interleukin (IL)-10-secreting regulatory B cells counteract the proinflammatory profile and improve glucose sensitivity. ..."

[jimmylegs]

Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice (2015)
https://link.springer.com/article/10.10 ... 015-9661-5

"Clinical improvement during pregnancy in multiple sclerosis (MS) patients suggests that sex hormones exert potent regulatory effects on autoimmune function. Our previous studies demonstrated that estrogen- (17β-estradiol; E2) mediated protection against experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, hinges on the B cells, leading to elevated numbers of IL-10 secreting CD1dhiCD5+ B regulatory cells (Bregs) in wild type mice."

[jimmylegs]

Progesterone synthesis in the nervous system: implications for myelination and myelin repair (2012)
https://www.frontiersin.org/articles/10 ... 00010/full

"... neuroendocrine research over the past decades has established that progesterone has multiple functions beyond reproduction. Within the nervous system, its neuromodulatory and neuroprotective effects are much studied. Although progesterone has been shown to also promote myelin repair, its influence and that of other steroids on myelination and remyelination is relatively neglected. Reasons for this are that hormonal influences are still not considered as a central problem by most myelin biologists, and that neuroendocrinologists are not sufficiently concerned with the importance of myelin in neuron functions and viability.
...
There are also major advantages to use natural progesterone in neuroprotective and myelin repair strategies, because progesterone is converted to biologically active metabolites in nervous tissues and interacts with multiple target proteins. The delivery of progesterone however represents a challenge because of its first-pass metabolism in digestive tract and liver. Recently, the intranasal route of progesterone administration has received attention for easy and efficient targeting of the brain. Progesterone in the brain is derived from the steroidogenic endocrine glands or from local synthesis by neural cells. Stimulating the formation of endogenous progesterone is currently explored as an alternative strategy for neuroprotection, axonal regeneration, and myelin repair.
...
Sources of Progesterone in the Central Nervous System
Progesterone is produced by the corpus luteum of the ovary ... during the luteal phase of the menstrual cycle in women.
...
progesterone is also a neurosteroid, which means that it is also synthesized within the nervous system. Thus, in addition to its endocrine mode of signaling, it acts on neural target cells via autocrine/paracrine mechanisms. The synthesis and metabolism of neurosteroids in the vertebrate nervous system have been extensively reviewed (Baulieu et al., 2001; Mellon and Vaudry, 2001; Do Rego et al., 2009; Pelletier, 2010). Progesterone synthesis involves conversion of cholesterol to pregnenolone by the side-chain-cleaving (scc) cytochrome P450scc, located at the inner mitochondrial membrane (Figure 2)."

[jimmylegs]

Progesterone Actions During Central Nervous System Development (2019)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533804/

"Although progesterone is a steroid hormone mainly associated with female reproductive functions, such as uterine receptivity and maintenance of pregnancy, accumulating data have shown its physiological actions to extend to several non-reproductive functions in the central nervous system (CNS) both in males and females. In fact, progesterone is de novo synthesized in specific brain regions by neurons and glial cells and is involved in the regulation of various molecu'lar and cellular processes underlying myelination, neuroprotection, neuromodulation, learning and memory, and mood. ...

[jimmylegs]

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances (2020)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079249/

"Diosgenin (DG), a well-known steroidal sapogenin, is present abundantly in medicinal herbs such as ... Dioscorea villosa ... DG is utilized as a major starting material for the production of steroidal drugs in the pharmaceutical industry. ... Numerous studies have reported that DG is useful in the prevention and treatment of neurological diseases. ... The present review mainly summarizes recent progress using DG and its derivatives as therapeutic agents for multiple neurological disorders along with their various mechanisms in the central nervous system. In particular, those related to therapeutic efficacy for Parkinson's disease, Alzheimer's disease, brain injury, neuroinflammation, and ischemia are discussed. This review article also critically evaluates existing limitations associated with the solubility and bioavailability of DG and discusses imperatives for translational clinical research. It briefly recapitulates recent advances in structural modification and novel formulations to increase the therapeutic efficacy and brain levels of DG.
...
Despite its pharmacological activities in the treatment of various diseases, the clinical application of DG is severely hindered by its low aqueous solubility, poor bioavailability and pharmacokinetics, and rapid biotransformation under physiological conditions [28].
...
8. Novel Formulations and Increased Bioavailability of Diosgenin
...
bioavailability of DG has been further improved by combining β-CD and liquid crystal DG to enhance the bioavailability of poorly water-soluble drugs "

well i thought we already figured out the water soluble thing long since, but it's been actual decades since i spent any time on the herbal side of things. more reading ahead

[jimmylegs]

No sex-specific difference in disease trajectory in multiple sclerosis patients before and after age 50 (2013)
https://link.springer.com/article/10.11 ... 2377-13-73

this does not make sense to me just yet...

[jimmylegs]

A pilot study of the effect upon multiple sclerosis of the menopause, hormone replacement therapy and the menstrual cycle (1992)
https://www.ncbi.nlm.nih.gov/pmc/articl ... 6-0026.pdf

"... Of the postmenopausal women 54% reported a worsening of symptoms with the menopause, and 75% of those who had
tried hormone replacement therapy reported an improvement. ..."