Progesterone--Mice

[Shayk]

Hi all

I’m happy to report that I think it’s finally time to start a progesterone thread.

I know the confidence level in mouse research (mine included) ranges from 0 to –0, but I wanted to initiate a timeline of the development of progesterone starting with the early research in mice. And, the mouse trials are off and running…..

Here’s some postive info (for the mice at least) and the studies have been on the traditional (EAE) and non-traditional (not auto-immune) animal models.

Effects of progesterone in the spinal cord of a mouse model of multiple sclerosis (auto-immune EAE model)

Clinically, PROG produced a moderate delay of disease onset and reduced the clinical scores. Thus, PROG attenuated disease severity, and reduced the inflammatory response and the occurrence of demyelination in the spinal cord during the acute phase of EAE

I found the second study (from Ectrims 2007) even more interesting because it appears to be based on a “not auto-immune” perspective of MS. It’s based on a mouse model that takes into account the research findings of Prineas and Barnett (oligodendrocytes die first).

Estrogen and progesterone treatment prevents cuprizone-induced demyelination

Barnett and Prineas (Ann Neurol 2004, 55:458) described extensive oligodendrocyte apoptosis and microglia activation in myelinated tissues of young MS patients with relapsing and remitting MS revealing no or few invading lymphocytes.

These data clearly indicate that both sex hormones are required to fully prevent cuprizone-induced demyelination in the CC. We conclude that P and E supplementation of MS patients may represent a valuable clinical tool.

Guys—note that this was a study in male mice and both progesterone and estrogen were found to “represent” a potentially valuable clinical tool.

Let’s hope clinical trials don’t take forever…I of course assume it will make it that far. The countdown begins.....

Since the Phase II Clinical Trial of progesterone in traumatic brain injury was positive I do have some confidence the mice research might actually translate to humans.

Take care all

Sharon

[Shayk]

Hi all

Those mice many of us so despise continue to do well with estrogen and progesterone. Here's another study:

Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis

RESULTS: Progesterone given prior to EAE induction attenuated the clinical scores of the disease, slightly delayed disease onset and decreased demyelination foci,

In turn, combined E(2) plus progesterone therapy more effectively prevented neurological deficits, fully restored LFB staining, MBP and PLP immunoreactivity and avoided inflammatory cell infiltration.

On the neuronal side, steroid biotherapy increased brain-derived neurotrophic factor (BDNF) mRNA.

CONCLUSION:.... Therefore, sex steroids should be considered as potential novel therapeutic strategies for MS.

I think the "news" here is that someone is at least considering both progesterone and estrogen.

Take care all

Sharon

[gibbledygook]

I added progesterone 50mg about 2 weeks ago and 25mg DHEA about a week ago as my hormone levels are all out of syn (low progesterone and luteinizing hormone). I have continued to enjoy considerable improvements in all of my deficits which began when increasing the herbs so there has certainly been no negative impact. I cannot determine any immediate improvement on taking them such as I noticed when I increased the salvia and scutelleria.

[Shayk]

Well, it's almost 2 years since I started this thread and we're still in mice (both EAE and a "not" immune model of MS).

I just wanted to pick up on some of the research on hormones, remyelination and neuroprotection.

Impact of sex steroids on neuroinflammatory processes and experimental multiple sclerosis

Besides regulating brain physiology, both steroids conciliate neuroprotection against toxicity and neurodegeneration.

Gender-specific prevalence of degenerative disorders might be associated with the loss of hormonal activity or steroid malfunctions.

Both hormones can individually mediate protection, but they are more effective in cooperation.

A second research line, using an animal model for multiple sclerosis, provides evidence that steroids achieve remyelination after demyelination

17beta-estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice

To evaluate the role of 17beta-estradiol (E) and progesterone (P) in prevention demyelination, young adult male mice

The combined treatment with both steroid hormones counteracted the process of demyelination.

These data show that sex steroids can protect the brain from demyelination and stimulate remyelination.

It appears that only the administration of both hormones is fully effective.

The positive hormonal influence on myelination in the CNS may be a future therapeutically strategy for the treatment of MS.

Progesterone neuroprotection in traumatic CNS injury and motoneuron degeneration

In traumatic brain injury (TBI), progesterone has the ability to reduce edema and inflammatory cytokines, prevent neuronal loss and improve functional outcomes. Clinical trials have shown that short-and long-term progesterone treatment induces a significant improvement in the level of disability among patients with brain injury.

SCI also causes oligodendrocyte loss and demyelination. In this case, a short progesterone treatment enhances proliferation and differentiation of oligodendrocyte progenitors into mature myelin-producing cells, whereas prolonged treatment increases a transcription factor (Olig1) needed to repair injury-induced demyelination.

Systemic progesterone administration results in a partial reversal of the age-associated decline in CNS remyelination following toxin-induced demyelination in male rats

I threw that one in since disability levels in MS are age related, we seem to lose the ability to re-myelinate, so an obvious question--is that related to declining levels of progesterone as we age?

Protective effects of progesterone administration on axonal pathology in mice with experimental autoimmune encephalomyelitis

Previous work has shown that progesterone attenuated the clinical severity, demyelination and neuronal dysfunction of EAE mice (Garay et al., J. Steroid Biochem. Mol. Biol., 2008).

Thus, progesterone also exerts protective effects on the axonal pathology developing in EAE mice

It's going to be a long slog...

Sharon

[jimmylegs]

hey there shayk, this kind of ties in with some other zinc work i was looking at so thought i'd mention it here:

The role of zinc in reproduction
Journal Biological Trace Element Research
Issue Volume 32, Numbers 1-3 / January, 1992
Abstract Zinc is a very important element in the reproductive cycle of species... different effects of zinc can be explained by its multiple action on the metabolism of androgen hormones, estrogen and progesterone, together with the prostaglandins. Nuclear receptors for steroids are all zinc finger proteins...

so far, i have looked at zinc mostly in terms of normalizing my uric acid (which is working) but recently was surprised by getting a very unusual response to my d3 regimen. since working to optimize my zinc status, my serum levels of d3 skyrocketed with a week of megadose supplementation, compared to earlier efforts.
i have been speculating that the change in response involves my d3 receptors - complete with their zinc fingers. i wonder if the zinc has altered my body's hormone metabolism too...?

[Shayk]

JL

I don't really have a clue if zinc may have altered your hormone metabolism. I did a quick Pub Med search and found 2 abstracts--sort of on topic.
Zinc deficiency and supplementation in ovariectomized rats: their effect on serum estrogen and progesterone levels and their relation to calcium and phosphorus

Findings of the study show that zinc deficiency causes a significant decrease in calcium and phosphorus levels and that zinc supplementation prevents these adversities in ovariectomized rats.

The effect of low dose zinc supplementation to serum estrogen and progesterone levels in post-menopausal women

Results of the study show that low-dose zinc supplementation to post-menopausal women for 2 weeks does not have a significant effect on the concerned parameters.

Now, I question if a 2 week trial of low dose zinc is adequate to come to the conclusion that it doesn't impact hormone levels. From the hormone angle, a minimum of 3 months at the prescribed dose is generally suggested prior to re-testing or gauging the impact.

Sorry I don't know more about it--but you might be interested in this general reference article (technical) about progesterone--over 800 citations and it's open access. Don't let the title scare you.

Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System

I must say though that when you get your nutrition levels where you want them, it's time to get your hormone levels tested.

Take care

Sharon

[Bubba]

Not real sure of the difference between progesterone and testosterone. They sound alike so they must be cousins or something like that... At anyrate, I have now been taking testosterone gel for about a month. It has increased my energy levels a bit, and I have regained some emotions. But other than that, not much.

[jimmylegs]

thanks for those links shayk - that one study seems like a waste of time. the low dose zinc one? 15 mg, and only administered for 2 weeks?
i don't have full text access to that journal i can't see day 1 levels or day 14 levels.
i'd be interested to see whether they came anywhere near 18.2 umol/L!

here's an abstract on new zealand rabbit pregnancy progesterone and zinc status... it's another journal i can't access, so i can't check out their methodology, but at least it seems to demonstrate a link between supplemental zinc and hormone levels.

http://www.ncbi.nlm.nih.gov/pubmed/1340755

The treatment of group 2 does with calcium carbonate, sodium phosphate dibasic, and zinc acetate in drinking water improved the serum progesterone, urine progesterone, and non-efficacious progesterone in addition to serum zinc and inorganic phosphate, which led to improvement of the number of matings/conception, litter size and litter weight, and lowered total mortality.

[Shayk]

Hey Bubba

Yeah, it's probably fair to say testosterone and progesterone are cousins. I can't say that I really know the difference either, although testosterone is generally considered a "sex" hormone and progesterone isn't. There was a Phase I Clinical trial of testosterone which had a positive outcome--it reduced brain atrophy. So, some of the impact may be "invisible"--but hopefully to your benefit since atrophy has been linked to disability.

JL

Here are some quotes (no citations) from the book "The MS Solution" by K. R. Simpson

Zinc Deficiency--As well as being important in overall pituitary function, zinc naturally inhibits the aromatase enzyme. When you are deficient in zinc, your estrogen levels may creep up.

If your estrogen level tests high...take 80 to 100 mg per day of zinc

Why do progesterone levels drop?.....(from a long list)Deficiences of Vitamins A, B6, and C and Zinc

Low zinc levels have been found in the CNS of people with MS. Zinc is a natural balance to estrogen, so it's very important for men with high levels of estrogen to take....

Men with high estrogen should take up to 80mg per day; everyone else should take 20-40mg daily

And, from another source, no citation, "progesterone normalizes zinc and copper levels"

Not very helpful I know....take care--remember too that progesterone is synthesized de novo in the brain and spinal cord.

Sharon

[jimmylegs]

neato!

[jimmylegs]

heya shayk, i got that article you sent. i have read that one before, the abstract anyway, but it finds zinc did not change the hormone levels.
it's because they only used 15mg/d for two weeks, and then they did the followup blood test at 4 weeks. i'm not surprised they found no effect!

now, the hormone replacement therapy *did* show lasting effects at 4 weeks out. but i don't have the background to assess the amounts they used for their daily HRT dosing.

[cheerleader]

Found something for you, Sharon Another piece?

Progesterone reverses the neuronal responses to hypoxia in rat nucleus tractus solitarius in vitro

In addition to stimulating the ventilatory response to hypoxia, progesterone exerts a neuroprotective effect on neurones during adaptive and pathological processes such as cortical hypoxia and ischaemia (Jiang et al. 1996). These stimulatory and neuroprotective properties may render progesterone useful as a treatment for patients suffering from chronic hypoxia.

http://jp.physoc.org/content/544/2/511.full

cheer

[Shayk]

Hey JL

I haven't read the article but will check it out and let you know if I have any comments on the hrt dosing.

Cheer

Terrific news--thank you--it's music to my ears.

It seems like estrogen might have an impact on hypoxia as well.

17beta-estradiol protects against hypoxic/ischemic white matter damage in the neonatal rat brain

Developing oligodendrocytes (pre-OLs) are highly vulnerable to hypoxic-ischemic injury and associated excitotoxicity and oxidative stress.

These results suggest a potential role for estrogens in attenuation of hypoxic-ischemic and oxidative injury to developing OLs

Hypoxia-induced apoptotic cell death is prevented by oestradiol via oestrogen receptors in the developing central nervous system

Maybe they are pieces to the puzzle.

Take care all

Sharon

[LR1234]

Any more news in the world of hormone therapy and MS??

[Filmmaker]

hum, very interesting... IF MS brain lesions and scar tissues are similar to the endometriosis process, progesterone should be the best treatment...