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Questions About Steroids
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Topic starter
30/01/2019 8:19 am
17AA steroids and increase Glucocorticoid receptor density Dunno if this was ever discussed before, but this particular abstract struck me as quite surprising.
quote:
Pharmacol Toxicol. 1995 Oct;77(4):264-9. Related Articles, Links
[3H]dexamethasone binding activity in liver microsomes is modulated differently by 17 alpha-alkylated androgens and testosterone in vivo.
Fernandez L, Boada LD, Luzardo OP, Zumbado M, Lopez A, Diaz-Chico BN, Chirino R.
Department of Clinical Sciences, Faculty of Health Sciences, University of Las Palmas de G.C., Spain.
Rat liver microsomes contain a single class of steroid binding sites, capable of binding various glucocorticoids and progesterone. In a previous article, we have described the in vitro interaction of several androgens with this binding site. Unlike natural androgens, the 17 alpha-alkyl derivatives Stanozolol and danazol were capable of interacting with this binding site through a negative allosteric pattern. Now, the effects these steroids exert on the microsomal [3H]dexamethasone binding site have been studied in vivo. The administration of a single dose of stanozolol to rats provoked a significant reduction in the microsomal [3H]dexamethasone binding capacity. This effect was maximal two hr after stanozolol administration and persisted for six hr. The restoration of the [3H]dexamethasone binding level after stanozolol administration was dependent on protein synthesis, since it was blocked by the concomitant administration of cycloheximide. None of the other androgens tested (danazol, methyltestosterone, fluoxymesterone, and Testosterone Propionate) was capable of provoking a similar effect when administered 2 or 24 hr prior to sacrifice. In rats treated for seven days with a daily dose of diverse androgens and sacrificed 24 hr after the last treatment, none of the 17 alpha-alkyl androgens assayed provoked significant changes in the microsomal [3H]dexamethasone binding level, although stanozolol, danazol, and methyltestosterone provoked a significant increase in glucocorticoid receptor concentration. In contrast, the administration of testosterone propionate provoked a 50% reduction in the [3H]dexamethasone binding level without causing changes in the glucocorticoid receptor concentration. These results provide new evidence on the existence of different effects on the liver of 17 alpha-alkyl androgens, compared to the effects produced by natural androgens.
Especially the one about stanozolol surprises me, since it is a LAG inhibitor.
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
30/01/2019 9:04 am
Good Post!!
30/01/2019 10:03 am
What in the heck is a LAG inhibitor?
Topic starter
30/01/2019 10:55 am
Low Affinity Glucocorticoid receptor Inhibitor
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
30/01/2019 11:51 am
Nice to see you posting again BC.
"The medals don't mean anything and the glory doesn't last. It's all about your happiness. The rewards are going to come, but my happiness is just loving the sport and having fun performing" ~ Jackie Joyner Kersee.
30/01/2019 12:51 pm
Low Affinity Glucocorticoid receptor Inhibitor
Ahhh.....
So, have you come across any further explanation for stanozolol increasing glucocorticoid receptor concentration? Or is it still a mystery?
Joint pains come to mind.winny is known for it. Inhibition of the glucocorticoid signaling cascade is the cause, but I'm not sure exactly what is going on to cause it, specifically.
The increased glucocorticoid receptor concentration would be an attempt to regain some normal homeostasis -- balancing sympathetic nervous tone, in order to counter the ever-increasing parasympathetic dominance during stanozolol usage.
Any thoughts?
Topic starter
30/01/2019 1:33 pm
So, have you come across any further explanation for stanozolol increasing glucocorticoid receptor concentration? Or is it still a mystery?
Can't say I have, but it seems indicative of a 17AA steroid, but with gradations and it seems to be quite the opposite with Fluoxymesterone. So I would postulate, and keep in mind this is just an educated guess, is that the alkyl group permits the proliferation of the receptors even if it doesn't activate them to any large degree. Especially given that the order of effect correlates with the affinity for GR. Again with the exception of fluoxymesterone, but in both cases that can be explained by fluoxy's strong inhibition of Gluco's.
quote:
Joint pains come to mind. Winny is known for it. Inhibition of the glucocorticoid signaling cascade is the cause, but I'm not sure exactly what is going on to cause it, specifically.
If that were the case, you'd be more inclined to see it with fluoxy, which is on the other end of that spectrum, and boldenone, which both block gluco's to a very large extent. With stanozolol there is even some evidence that it activates these receptors instead of inhibiting them. But either way, it didn't have any notable activity.
quote:
The increased glucocorticoid receptor concentration would be an attempt to regain some normal homeostasis -- balancing sympathetic nervous tone, in order to counter the ever-increasing parasympathetic dominance during stanozolol usage.
Any thoughts? [/B]
With steroid hormones we often see a potentiating action on homo-receptor proliferation. Just like androgen use over time, especially initially, can create more androgen receptors, gluco's tend to upregulate as well.
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
Topic starter
30/01/2019 2:09 pm
Nice to see you posting again BC.
I still get mail notifaction of old threads I was active in Yeah, I know, my life has been getting in the way, but you guys should see how hectic it is here since the baby.
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
30/01/2019 2:56 pm
so brin us up to date my firend!
jb
Topic starter
30/01/2019 3:48 pm
Well, January 31st my lovely gf Wanda gave birth, in a relatively easy labour of under 5 hours, to a then still blue, wrinkly and particularly digusting creature. But by the next day he had already turned into a beautiful pink miracle known as Brennan Karl. We'd been living on our own since september and things had been rough as I was still without a job, being very regionally bound now with the child, and there being so few jobs for my qualifications in this region. In the mean time I am working though, although my function involves too much administration and too little hands on work to be sufficiently to my liking, and certainly not in a pay-range I want to spend too much time in while I'm the only one supporting the three of us.
Since then its been a very busy mix of joy and pain, with the joy being watching my beautiful (who'd have thought I'd ever think of a baby as beautiful, I usually find them quite hideous) son growing up, and the pain part mostly in relation to the strain he puts on our time and relationship. But we cope though. It's extremely rough financially for the moment, we have enough to get by but nothing to set aside right now, and well, my career isn't where I (or anyone really) had expected it to be.
But all in all, coming home overworked, tired and slightly depressed, my mood still lightens when I see him, and despite the way this messed up my life, I haven't regretted my decision for a moment. He's perfect. he's what I always dreamed of. Being a father is the greatest thing in the world.
Good things come to those who weight.
The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.
30/01/2019 4:24 pm
Can't say I have, but it seems indicative of a 17AA steroid, but with gradations and it seems to be quite the opposite with Fluoxymesterone. So I would postulate, and keep in mind this is just an educated guess, is that the alkyl group permits the proliferation of the receptors even if it doesn't activate them to any large degree. Especially given that the order of effect correlates with the affinity for GR. Again with the exception of fluoxymesterone, but in both cases that can be explained by fluoxy's strong inhibition of Gluco's.
But couldn't it maybe be tissue specific, as is the case with SERMs like http://search.store.yahoo.com/cgi-bin/nsearch?catalog=yhst-20189112917352&query=tamoxifen&.autodone=http%3A%2F%2Fwww.cemproducts.com%2Fnsearch.htm l" target="_blank" rel="noopener">tamoxifen, which antagonize breast tissue, but agonize many other tissues?
There is definitely a correlation with the alkyl group, but it can't be the only variable, I would tend to think. I can't think of any exceptions right now, but I have to wonder if ATD shares this property while lacking the 17aa (just a wild guess).
quote:
If that were the case, you'd be more inclined to see it with fluoxy, which is on the other end of that spectrum, and boldenone, which both block gluco's to a very large extent.
But there is much more to glucocorticoid signaling then just receptor antagonization.
And it gets more complicated beyond that as well. Consider boldenone's characteristic cardiovascular endurance improvement aspect: I am willing to go out on a limb and say it might be related to AMPk increased as a downstream result of increased nitric oxide synthase. But if the GR truly were being antagonized to a great degree, and glucocorticoid signaling inhibited significantly, the point would be moot. There would be no endurance improvement in the absence of sympathetic nervous tone.
Of course, this is assuming the endurance improvements aren't simply a myth in the first place.
Also, joint pains and a drag-ass feeling are not too commonly reported with boldenone. Users tend to feel pretty good.
So what is it we don't know/understand? Am I alone missing something? Or is there a missing link to our understanding in general in the glucocorticoid signaling cascade?
Take http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&list_uids=1521941 4" target="_blank" rel="noopener">this study for example. It shows that some AAS inhibit glucocortoid signaling in a manner other than GR affinity.
quote:
With stanozolol there is even some evidence that it activates these receptors instead of inhibiting them. But either way, it didn't have any notable activity.
I can buy that.
But does the evidence lean towards tissue specific, or just very, very low potency?
Congratulations on the birth of your son, by the way.
.