In Krauss and Williams et al research on lipoproteins in Bay Area Mormon kindreds, they talked about my favorite things (other than the sound of music)... on their relationship with HDL2b, the regression lipoprotein subfraction which performs in the vasculature like liquid D-R-A-N-O:
--young age
--low BMI/fat body composition
--more alcohol (for women only -- j/k --the stats didn't reach significance)
--estrogen (for getting our both mojo-jo-jo and HDL2b on) -- both natural and substituted
Estrogen has great affects on improving HDL2b from birth to menopause for women (and men too?). And after menopause, women have a pattern of elevated HDL3c/3b like men (not pretty -- the blip above for 3b is even greater than the 3b blip for men Fig 1 below). Not shown in the data or graphs, the authors note that for the subjects taking estrogen replacement did display greater levels of the larger-sized HDL3a and HDL2a. No mention of HDL2b which was odd since estradiol has been shown to increase HDL2b quite significantly in menopausal women. The authors also didn't report the specific type of estrogen estradiol (better) v. Premarin (bad).
I found this article so neat on many levels -- the authors really focused on subfractions of a previously under-appreciated lipoprotein ignored by statinators, the HDLs 'happy' good cholesterol. They are not from a major medical academic institution (LBL does not have that distinction around here). And lastly they used technology that we love at TYP to 'track' health/health status.
-BG
Dear G,
ReplyDeletethis is a great point that you raise. The missing element in all these lipid studies is the (full) hormone panel.
what is the role of hormones? Life, Reproduction and Death.
My doc says, from a Palaeo perspective, the individual is only supported by nature to 35ish.. long enough to reproduce and protect the offspring until 15+ish. Then Nature would prefer to release the earth resources to younger tribe members coming through, ie oldies need to move to the next life.
If the current palaeo/evolutionary view of eating habits holds up as a theory, then a similar perspective on hormones and life span can be argued too.
But, us over-35ers on t-nation want to hang on as long as possible.. and our perspective changes with years. For example, I could never fathom why the aborginal elders procreated with the younger females while the young males were sent on walkabout for years. Well, being at an age where i should act like an elder, i now understand and fully support every clever aspect of the above notion where age has separated out longevity and health genes.
To that end a full hormone panel at age 35 is to me as important as writing a Will.
That includes IGF-1 etc. It has taken me 18 months to lift my IGF-1 from the mean of a 90 year old male to the mean of a 40 y old male. Its a TYP attitude. Give me numbers.
re estrogen, I now prefer the use of the plural, estrogens, mainly because( like the clever boys at t-nation), we cogniscenti prefer to hold our E2 levels at 20 ng/dl . That seems to be the peak of the curve for physical parameters , that include adiposity, emotional factors , libido and muscle strength. Its a sharp, narrow curve.
Taking E2 further, through Peter Tunbridge's recent book, i use his hypothesis that the metabolites from the liver of E2 above a certain value are switched from
2 alpha hydroxy estrone to 16 alpha etc. I dont yet know what this value is as I have a liver CYP4501A1 abnormality. His view is that this switch over from 2 alpha to 16 alpha has pivotal implications downstream in the celular response to metabolising of carbs away from glycogen towards fatty acids.
Main controls identified by Tunbridge are E2 level, Progesterone level and age.
I am testing that and other controls on me, the lab rat. Progesterone level is purported to be the hormone to be monitored and managed to control the set points for E2 levels and DHT .
My knowledge is only superficial compared to yours ,... I am delighted, for your husband's and children's sake , to see your interest in estrogen(s) at your youthful age... an age where you have time on your side! I wish I did, now i have to fight every step.
best
john
aust
DR J,
ReplyDeleteThanks for all the estrogen info -- actually I'm just starting to look at it! The book sounds great -- I really appreciate the recommendation. DR. T sounds amazing. From my experience Progesterone really is powerful (esp when excessive!!)...
This physician also comes highly recommended:
hormonesbyhart.com
Your insights are wonderful. I think I think like you similarly regarding athletes... athletes appreciate hormones for more than mere mortals b/c it involves PRs (personal records -- them competing against themselves (or the world)). I've wondered what is the point of hormones sometimes? Why do we women need to bleed down our legs E V E R Y #$#&*@ M O N T H ?
Hormones rule everything...as you've probably discovered and unlocked many secrets by seeing the IGF-1 go up. My appreciation grew as the E deficiency worsened...
Hormones control power, performance and procreation. If I were an elder... I'd send you away *ha*! I wonder what stories you have about your 'walkabout'?!
What is the balancing point between elite reproductive health and elite longevity? Do you think they are equivalent?
-G
Dear G,
ReplyDeletere "What is the balancing point between elite reproductive health and elite longevity? Do you think they are equivalent? "
Being cheeky, and as I am going away for the weekend, I throw the ball back over to you, .....one needs to first define "elite". That will give the terms of reference, the path to the answer falls out then.
Now here is something practical. I am going to get some of this from the USA. The success will likely be the suspension base to pump the ingredient through the skin . It also may need an enzyme pre-treatment first to cut the outer horny layer of skin. Plus some niacin to give a flush increase the blood flow near the skin might be good.
Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans.
Harada N, Okajima K, Narimatsu N, Kurihara H, Nakagata N.
Department of Translational Medical Science Research, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Sensory neurons release calcitonin gene-related peptide (CGRP) on activation. We recently reported that topical application of capsaicin increases facial skin elasticity and promotes hair growth by increasing dermal insulin-like growth factor-I (IGF-I) production through activation of sensory neurons in mice and humans. Raspberry ketone (RK), a major aromatic compound contained in red raspberries (Rubus idaeus), has a structure similar to that of capsaicin. Thus, it is possible that RK activates sensory neurons, thereby increasing skin elasticity and promoting hair growth by increasing dermal IGF-I production. In the present study, we examined this possibility in mice and humans. RK, at concentrations higher than 1 microM, significantly increased CGRP release from dorsal root ganglion neurons (DRG) isolated from wild-type (WT) mice and this increase was completely reversed by capsazepine, an inhibitor of vanilloid receptor-1 activation. Topical application of 0.01% RK increased dermal IGF-I levels at 30 min after application in WT mice, but not in CGRP-knockout mice. Topical application of 0.01% RK increased immunohistochemical expression of IGF-I at dermal papillae in hair follicles and promoted hair re-growth in WT mice at 4 weeks after the application. When applied topically to the scalp and facial skin, 0.01% RK promoted hair growth in 50.0% of humans with alopecia (n=10) at 5 months after application and increased cheek skin elasticity at 2 weeks after application in 5 females (p<0.04). These observations strongly suggest that RK might increase dermal IGF-I production through sensory neuron activation, thereby promoting hair growth and increasing skin elasticity.
If this works, your girlfriends will love you forever,
http://www.ncbi.nlm.nih.gov/pubmed/18321745?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
John!
ReplyDeleteSo we know (naturally) elevated IGF-1 reduces Lp(a) (and many other benefits) and thus improves longevity. Raspberry K will make your hair grow back and improve your ummm.... cheeks ;)
Now that is an elitely dangerous combo... Australian accent, nice cheeks *hee*, ripped abs and bountiful HAIR... watch O U T!
My girlfriends however may get a little bit pissed if they grow hairy faces... I'll send them to Australia to my friend John!!
-G
G!
ReplyDeleteTwo Points
1. Your HDL subdivision is so good that Dr Davis should co-author a paper to LEF.It is truly valuable as is.. now, will you tell him or will he mozzie over here by himself?
2. re your girlfriends, girls are absolutely paranoid about the lines around the eyes. If this works and, they keep it to this area , then it might help the eyebrows become more luscious and they will doublely love you. If they put it on their chinychins and they sprout , then ( as this would only happen under boys dihydrotestosterone), i might suggest that your friends might actually be cross-dressers etc... there is a lot of funny lines here but that's for another day.
My first test will be the backs of my sun ravished hands so if i turn into a werewolf, then you might just be right. Ordered the stuff, I'll will report when the goo is ready.....
Also don't forget figure athlete, in particualr, http://www.figureathlete.com/free_online_article/training/the_final_nail_in_the_cardio_coffin
Rachel does not have any LDL's to worry about.
I'm off for a few days
John,
ReplyDeleteYes, Dr. D waunders over here when he was time occasionally :)
The Rachel is AWESOME!
Funny lines...
-G
G,
ReplyDeleteI hope you don't mind me using this post to put up interesting lipid issues that result from thinking about your post...
http://www.ncbi.nlm.nih.gov/pubmed/16713234?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters.
Wilson TA, Nicolosi RJ, Woolfrey B, Kritchevsky D.
Department of Clinical Laboratory and Nutritional Sciences, Center for Health and Disease Research, University of Massachusetts Lowell, Lowell, MA 01854, USA. thomas_wilson@uml.edu
Our laboratory has reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Because RBO has a greater content of the unsaponifiables, which also lower cholesterol compared to most vegetable oils, we wanted to know whether oryzanol or ferulic acid, two major unsaponifiables in RBO, has a greater cholesterol-lowering activity. Forty-eight F(1)B Golden Syrian hamsters (Mesocricetus auratus) (BioBreeders, Watertown, MA) were group housed (three per cage) in cages with bedding in an air-conditioned facility maintained on a 12-h light/dark cycle. The hamsters were fed a chow-based hypercholesterolemic diet (HCD) containing 10% coconut oil and 0.1% cholesterol for 2 weeks, at which time they were bled after an overnight fast (16 h) and segregated into 4 groups of 12 with similar plasma cholesterol concentrations. Group 1 (control) continued on the HCD, group 2 was fed the HCD containing 10% RBO in place of coconut oil, group 3 was fed the HCD plus 0.5% ferulic acid and group 4 was fed the HCD plus 0.5% oryzanol for an additional 10 weeks. After 10 weeks on the diets, plasma total cholesterol (TC) and non-high-density lipoprotein cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the RBO (-64% and -70%, respectively), the ferulic acid (-22% and -24%, respectively) and the oryzanol (-70% and -77%, respectively) diets compared to control. Plasma TC and non-HDL-C concentrations were also significantly lower in the RBO (-53% and -61%, respectively) and oryzanol (-61% and -70%, respectively) diets compared to the ferulic acid. Compared to control and ferulic acid, plasma HDL-C concentrations were significantly higher in the RBO (10% and 20%, respectively) and oryzanol (13% and 24%, respectively) diets. The ferulic acid diet had significantly lower plasma HDL-C concentrations compared to the control (-9%). The RBO and oryzanol diets were significantly lower for plasma triglyceride concentrations compared to the control (-53% and -65%, respectively) and ferulic acid (-47% and -60%, respectively) diets. Hamsters fed the control and ferulic acid diets had significantly higher plasma vitamin E concentrations compared to the RBO (201% and 161%, respectively) and oryzanol (548% and 462%, respectively) diets; the ferulic acid and oryzanol diets had significantly lower plasma lipid hydroperoxide levels than the control (-57% and -46%, respectively) diet. The oryzanol-fed hamsters excreted significantly more coprostenol and cholesterol in their feces than the ferulic acid (127% and 120%, respectively) diet. The control diet had significantly greater aortic TC and FC accumulation compared to the RBO (115% and 89%, respectively), ferulic acid (48% and 58%, respectively) and the oryzanol (74% and 70%, respectively) diets. However, only the RBO and oryzanol diets had significantly lower aortic cholesterol ester accumulation compared to the control (-73% and -46%, respectively) diet. The present study suggests that at equal dietary levels, oryzanol has a greater effect on lowering plasma non-HDL-C levels and raising plasma HDL-C than ferulic acid, possibly through a greater extent to increase fecal excretion of cholesterol and its metabolites. However, ferulic acid may have a greater antioxidant capacity via its ability to maintain serum vitamin E levels compared to RBO and oryzanol. Thus, both oryzanol and ferulic acid may exert similar antiatherogenic properties, but through different mechanisms.
Dr J!!
ReplyDeleteThis is A W E S O M E...and so are YOU!!! Let me know if you try it (oryzanol) out. Fats certainly are important I'm finding... for 'Life Reproduction and Death' as someone very wise said!
I'm trying to get up to speed before I hit Peter Tunbridge...trying to slog my way through the 'basics' with DR.John R. Lee (what ur doctor didn't tell u about menopause).
My nutritionist sells rice bran oil (RBO) for cooking/eating. Now I know what he's talking about! So perhaps the Okinawan, Asian/Mediterr-Asian diet with brown rice + fish is best for insulin sensitivity, hormesis, and anti-inflammatory status? What do you think?
THANK YOU!
-G
Dear G,
ReplyDeleteAh, shucks..it takes a genius to recognise one...wait till we turn your husband into Tarzan...
You have some truly remarkable research people in the US.. its our task ( and a delight) to find them and synthesis a optioned up plan, I reckon.
Now... On how i found oryzanol ...and from that you may be able to deduce how i connect the dots ..
Firstly I am rather superficial in my R&D efforts, tempus fugit, rather I depend on key people like the TYP mob ie u, and synthesize options from their/ur efforts.
For example, every day I scan Mike Adams and trust his views, well, broadly.. he ran an article on brown rice protein drink here http://www.naturalnews.com/023547.html which I followed up in detail and have decide to buy it when they service australia.
But recently they sent an email that said ........" Have you ever heard of Gamma Oryzanol? The Japanese have been using and studying this natural compound for years. Gammo Oryzanol is found in different parts of rice, in particular the Rice germ and Rice Bran. What the Japanese have found is that Gammo Oryzano increases muscle mass, is a potent anti-oxidant and is very effective in healing ulcers and other things. Well, guess what Because Sun Warrior Protein is made from Bio-Fermented Raw Sprouted Whole Grain Brown Rice (with the bran and germ) is has Gamma Oryzanol in it. Gamma Oryzanol stimulates the release of endorphins - the body's so-called "feel good" hormones. These hormones stimulate the pleasure centers of the brain, and this stimulation results in an elevation of mood."
Now I said yeah yeah and then checked pub med and hey presto..the above popped up.. I dont know if there is enough Oryzanol in it , or even if it works or anything ...but if it is there then it saves buying as pills from iherb.com ..I found their email support rather pathetic and their website dorkie but if it works it works.. (iherb.com could always be a back up and your RBO supplier might help vs a pill from iherb.)
I like the idea of going off fast acting hydrolysed whey and onto this as a test.
And yes I like the idea of your diet.. when I was in Shanghai this january, there were NO FAT people there , they hardly eat rice, only vegies ( mainly cabbagey sort of things) and meat, often in a soup ..
BTW, to makes things a bit simpler , my starting daily diet plan is 100gm of proteins, 50gms of fats, 25 gms of carbs.. and then I adjust down in meals according to the day as it evolves and sometimes I .. cheat. I am finding it a mental struggle to get smaller and drop down to 10% body fat.
so nice to hear from you !
j
G,
ReplyDeletethought of something..
if you think this oryzanol/RBO has legs, can you put it up for Dr Davis to think about for his testing panel of freely available things over the counter to reduce chol? i'll stick to my gene/hormone thread there
I still think that you 2 should publish a note on your HDL work..
dr j said...
ReplyDeleteG,
thought of something..
if you think this oryzanol/RBO has legs, can you put it up for Dr Davis to think about for his testing panel of freely available things over the counter to reduce chol? i'll stick to my gene/hormone thread there
I still think that you 2 should publish a note on your HDL work..
September 11, 2008 12:36 AM
Dr. B G said...
dr j,
You are TOO brilliant funny...and !!humble... I think connecting dots is definitely your specialty.
The iHerb.com people are curious.
What a great warrior meal plan. Ripped abs and blue-eyes will indeed be a very dangerous combination.
The oryzanol appeared effective for raising HDLs and lowering TGs in hamsters. Did you notice the authors discussed how oryzganol did NOT work in another experiment when cholesterol was not provided? Interesting huh? I don't now what Tunbridge's ideas are on this but, but John R. Lee discusses the importance of dietary cholesterol for hormone synthesis. Statinators rot. The backlash with Pharma-induced cancer is coming now (SEAS trial, etc).
Your perceptions are incredible. Shang-hai also has more beautiful people than the rest of Asia (my little brother empirically observed). (My mother-in-law is from Shanghai)
-G
G
ReplyDelete1. Shanghai first!
Shanghai men are tall, good looking ( according to my GIM...short for.. girl I married) and are much better cooks than girls. So there is hope that your husband inherited those genes from his mum. The thing I especially like about Shanghai was that they have different electricity plugs to the rest of china but have THE SAME as us in australia! we ahve connection ..unbelievable. AND, our " dear boy", who is playing golf in Florida comes from Shanghai too ! he only stayed with us for 18 months but it was like a lifetime. i taught him the australian custom of "affectionate abuse", the more you love someone, the ruder you are to each other. Never know, your paths may cross. Fabulous family. I was pretty restrained in Shanghai, tell your brother, I only fell in love with 100 girls there.. well, it was only 2 weeks.
2. re oryzanol
just mentally doodling.. do you think that the oryzanol is/was bound to (a) the chol before, or (b) during transport through the gut wall, or (c) after liver. I tend to think of dietry chol like an import /export company. Dietry chol is imported in/as food and part exported back out along the gut ..liver chol on the other hand is manufactured according to signalled need or out of control signalled need ( my process engineering coming out here). I really like how you are looking at subfractions , because with this paradigm, then we can think in terms of particle surface modification eg, attachment of molecules such as, eg, oryzanol, to certain fractions which will then look different to potential separation mechanisms in the body which then may make it easier for elimination by export through gut wall or bile. Wish i had a white board to talk to you to clarify this ignorance....
3. back to Shanghai. There is a lot of activity on mitochondrial biogenesis in pub med starting and the boys in Shanaghai are right up there. In a recent set of abstracts, they found a lot of mito repair and improved performance with acetyl-l-carnitine and r-alpha- lipoic acid, both of which my doc has me on at the same levels! (I guess its a bit like just looking after the factories that have to use the fats and oils we shovel in our mouths! Here is an example-
A combination of nutriments improves mitochondrial biogenesis and function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats.
Shen W, Hao J, Tian C, Ren J, Yang L, Li X, Luo C, Cotma CW, Liu J.
Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
BACKGROUND: Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA), and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-alpha (Ppar alpha), peroxisome proliferator-activated receptor-delta (Ppar delta), and carnitine palmitoyl transferase-1 (Mcpt-1) and activity of mitochondrial complex I and II in skeletal muscle. All of these effects of mitochondrial nutrients are comparable to that of the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain. CONCLUSIONS/SIGNIFICANCE: These data suggest that a combination of mitochondrial targeting nutrients may improve skeletal mitochondrial dysfunction and exert hypoglycemic effects, without causing weight gain.
I am going away on tuesday for 10 days..
J,
ReplyDeleteI'll miss your wildly insightful comments while your gone -- have fun!
Are you my muse? Did you say PPAR delta? Now this has got my attention now! D**MN, Peter was right -- it's all about the mitochondria! 'Power Sex and...' mitochondrial biogenesis!!!
Might have to visit Shanghai next time with my BIM...ur making my sides hurt...
My friend (who I have yet to meet -- he apparently would like to hear my...umm ideas -- I'll share YOURS too) Bruce Ames from UC Berkeley sells Rejuvenon which contains Carnitine and Lipoic acid. He'll be upset that you're not buying it from him (maybe ru?)! Isn't that great stuff? Now I know why... it benefits our little nuclear POWER plants/mitochondria.
-G
dr j,
ReplyDeleteI'm sorry -- I didn't see your blog... sorry so you heard of Ames?
UR RIGHT!!!
Bile acids -- these are fantastic things... Fiber fatty acids and proteins are important to activate these -- they bind LXR and FXR which ultimately reduce bodily inflammation, promote longevity and reduces CAC scores.
Taurine -- from seafood -- u kno I'm into this now right? did you read my recent TYP forum posts?
-G
Hullo G,
ReplyDelete1. Ans..I hang off your every word .. anybody who has M**** friends, has my attention.. i had to google what it meant.. made me blush.
2. Sunday chit-chat.. let us be cheeky and say that LDL is actually good .. high LDL says something in the adrenals is wrong and stop searching in the liver and arteries .
a. consider it from a chemical engineering perspective Just for DHEA, Young Men produce about 31 mg DHEA daily, women, about 19 mg. DHEA has a half-life of 8-11 hours. But as we age, the process efficiency drops off and we are left with more LDL if the liver gets no signal to throttle back the production.
Reading p 261-262 of Clinical Gynecologic Endocrinology and Infertility By Leon Speroff, Marc A. Fritz
http://books.google.com.au/books?id=iyhIUSiNOfIC&pg=RA2-PA261&dq=ldl+and+pregnenolone&sig=ACfU3U0RJ2OSE0qfLbqnEc1S3MY0UucgrA
if this url is broken, search term is LDL and pregnenolone.
They say as an example, "estrogen increases placental P450scc enzyme activity that converts cholesterol to pregnenolone." The text is littered with references to LDL receptors, estrogen etc.
b. I have high LDL, lower quartile adrenal hormones/steriods and had mod. high Blood Pressure. Now as an experiment that worked, we jumped over the conversion point and added pregnenolone. Starting 2 weeks ago, 3 hours after taking pregnenolone, blood pressure dropped from 144/90ish to 108/72ish. It lifts to 122/82 ish during middle of the day and returns to 108/72ish after the preg pill. Neat eh?
My reasoning is that my adrenals have fallen down in converting LDL to the large MASS demand of adrenal compounds needed, ie high LDL results if no siganaling back to the liver. Now with the added preg, some of my downstream compounds needed can be made ie those that lowers BP.
So there you are G, hormone mass reaction kinetics in adrenals is my passion at the mo..
In signing off, I told my doc that after having my hormones levelled , I have had a revelation- I am acutely aware of being in love....... with estrogen ( and the carriers are not so bad either). He just smiled...
B4N
j
hullo G,
ReplyDeletethis is what I wanted to show you.
This is the sentence.."ACTH increases the number of low-density lipoprotein (LDL) receptors resulting in increased cholesterol uptake, the precursor for the biosynthesis of all steroid hormones." note the amount of cortisol produced too.
This is why I am mentally advancing just enough knowledge about interactions between chol/mito/hormones rather than too much in any one field. I am too old !
http://www.endotext.org/adrenal/adrenal5/adrenalframe5.htm
Mechanism of ACTH action on adrenal cortical cells
ACTH enters the systemic circulation and binds to specific high affinity receptors located on the surface of adrenal cortical cells and the skin. The adrenal cortex is composed of three zones. The outermost zona glomerulosa produces aldosterone, the middle zona fasciculata produces cortisol, and the innermost zona reticularis produces androgens. The steroid hormones produced by the adrenal cortex are classified as 21-carbon (the glucocorticoids, mineralocorticoids), 19-carbon (adrenal androgens) and 18-carbon (adrenal estrogens). Cortisol, the main endogenous glucocorticoid, is synthesized in the adrenal cortex under the exclusive regulation of ACTH. The adrenal cortex produces approximately 25 mg cortisol per day, 0.1 mg aldosterone and 10 mg of the adrenal androgen dehydroepiandrosterone (DHEA). ACTH is the principal regulator of cortisol production by zona fasciculata while it is of secondary importance in aldosterone and adrenal androgen production. The mechanism of ACTH action follows the classical peptide hormone rules. Indeed, ACTH binds to its receptors located on adrenal cell membranes activating a Gs-protein resulting in an increase of intracellular cyclic adenosine monophosphate (cAMP). ACTH stimulates cortisol synthesis and secretion by affecting several steps in the steroidogenesis pathway: (a) ACTH increases the number of low-density lipoprotein (LDL) receptors resulting in increased cholesterol uptake, the precursor for the biosynthesis of all steroid hormones. Indeed, while the adrenal cortex can synthesize cholesterol, almost 80% of the cholesterol used in steroid synthesis derives from sources outside the adrenals. (b) ACTH stimulates the cleavage of the side-chain of cholesterol, converting it to pregnenolone, the first and rate-limiting step in cortisol production. The CYP11A1 gene encodes the cholesterol side-chain cleavage enzyme, cytochrome P450(scc). Expression of CYP11A1 is controlled by ACTH and the steroidogenic factor 1, SF-1 (1). (c) ACTH hydroxylates pregnenolone to give to 17-OH-pregnenolone, which then travels to the endoplasmic reticulum for conversion to 11-deoxycortisol. 11-deoxycortisol moves back to mitochondria where another hydroxylation takes place at position 21 to produce the final product, cortisol. Cortisol is not stored in the adrenal cortex but is promptly secreted. The adrenal cortex synthesizes cortisol to maintain its normal serum levels for only few minutes. Thus, the effect of ACTH on adrenal cortisol production can be measured in the serum within minutes from its induction.
all the best
j
hi j,
ReplyDeleteThanks so much for sharing your observations. You know it's very helpful for me understanding my own hormone balance.
1. Blush...?? Hormone mass/metabolism kinetics makes me blush!
2. Cheeky -- Are the TG/HDLs ok? I'm glad your at TYP *smile* I'm always blown away by the level of sophistication, knowledge, dedication...AND...testosterone there!
a.Role of DHEA is critical as are each level of steroid-genesis (am finding from own deficiency/excess experiences). Thanks for the adrenal link -- I've been looking at that (it's in line with John Lee too). Us men and women are actually not built that differently.
b. A strong link between pollution (estrogenic-compounds) and excessive omega-6 fatty acids (n-6 PUFAs) and massive deregulation of hormone synthesis (pre-conception, infertility, in utero, ex utero, as we age).
ACTH, preg, and cortisol all control and regulate blood pressure -- for intensive responses like bursts of running/escaping predators and chasing prey (or skirts *wink*). Or exercise...hunting...indoor sports.
Your pregnenolone experiment does make sense... that's fantastic proof of your theory. Do you think the CYP11A1 are not working optimally? WOW I wasn't aware about the relationship between LDL receptors and ACTH -- but makes sense too -- cortisol is a cholesterol-based chemical structure. The raw ingredients are necessary for its production. The chemical engineering and negative feedback loops for supply/demand of hormones that you discuss are evident. They are ingrained in our human bodies don't you think? The purpose is honed to perfection over the last few millenia. Without traffic, travelling or atrocious grains.
I was on testosterone cream for a short while. Your corollary experience is not a surprise. Fish oil and vitamin D (the reproductive regulator of seasonal life as we know it on earth) affect the function of the aromatases, desaturases and CYPs.
So many people seem to report burnt out adrenals. Why do you think? Are we too stressed out? Not taking enough siestas/naps/sleep? Do we all have meditation-deficiencies?
-G
G,
ReplyDeleteIf you have trouble getting Peter Tunbridges book ,"The Human Code" either try this australian number 61-1-300-853-621 or ask me to follow up and send it... I could send it to your friend R, for example. Again, his working hypothesis is that most of our degenerative creep-up-on-us diseases are related to estrogen metabolism as we age. I read it 4 times . If you dont enjoy it, then I will pay the price in the afterlife!
catch you later
j
Dear G,
ReplyDeleteOn insulin sentivity and fat metabolism,
this is pretty good for me
http://www.t-nation.com/free_online_article/sports_body_training_performance_bodybuilding/mondays_with_thibs_beef_up_your_body_composition
today's article on t-nation
best
j
Hi j,
ReplyDeleteThanks for the information! I will check out both -- the book and the T-nation article.
-G
Hullo G,
ReplyDeleteam on holidays but just cant keep away from the computer.. and found some fabulous stuff that I wanted to share with just you, some of which appeals to our sense of humor!
muscle resistance training with a difference
http://www.carolynsfacialfitness.com/FacialFitness.html
http://www.shapeyourface.com ( the forums are fun)
statins and mitochondria
http://www.spacedoc.net/
http://www.spacedoc.net/board/viewtopic.php?t=1290&start=0
page 15 item 4c where he talks about MCT as the only fats that can be reacted on mitochondria without carnitine !
http://209.85.173.104/search?q=cache:-H4EPTqlMeQJ:www.umdf.org/atf/cf/%257B28038C4C-02EE-4AD0-9DB5-D23E9D9F4D45%257D/ThinkMitochondria.pdf+think+mitochondria&hl=en&ct=clnk&cd=1
thinkmitochondria umdf.org ifthe avove does not work.
back home in 3 days if above links fail.
B4N !
dr john
John N,
ReplyDeleteThanks! (where ever region you are?)
The facial link is funny -- I laugh a lot -- does that count??
Interesting discussions on the space-doc site! Did you know that astronauts routine take vitamin D while in space (though I can't find out from the local astronauts what ?DOSE).
Getting a tour of Dr. Ames lab in a couple wks -- I better bone up on my mitochondrial science!
I'm so grateful for your thoughtfulness and forwards!!
-G
It seems that minuscule vitamin d supplementation (300 IU) may raise LDL in long term in post-menopausal women who also get hormone therapy:
ReplyDeletehttp://www.labmeeting.com/paper/22280578/heikkinen-1997-long-term-vitamin-d3-supplementation-may-have-adverse-effects-on-serum-lipids-during-postmenopausal-hormone-replacement-therapy
Neonomide,
ReplyDeleteI never look at increases in LDL as bad v. good. The trials need to do NMR like in this post do determine the atherogenicity of the particles.
There is no question that both synthetic and natural estrogen raise HDLs -- and this is what the researchers found.
What they missed was that in the vitamin D3 300 IU/day group, the Trig increase effect over 3 yrs was the LEAST compared to all other arms. Vitamin D does improve insulin sensitivity.
HDLs reductions occur with age with and declining hormones. The researchers found this as well.
However in the vitamin D3 alone group experienced the LEAST amount of HDL declines. Yes the LDL did increase -- but probably these were likely (conjecture on my part) more buoyant than the 3 other arms. Too bad they didn't conduct NMR.
Synthetic progesterone -- they used cyproterone. Across the board, ALL synthetic progestins are BAD. They raise insulin, inflammation, hsCRP and guess what Trigs and lower HDLs. The authors saw this as well -- it was NOT vitamin D negating the lipoprotein effects, it was the Progestin. (see Figure 1)
I just a year of progestin H*LL... They suck.
The dose 300 IU of vitamin D3 is better than none. Here in the U.S.A. the pediatric academy advises 400 IU for newborns!
Thank you for your comments!
-G