[Lotus]

Yeah! You didn't leave! And, as always, you look great, Lotus. What new brand of PM are you trying out?

What's up eloise?,

Yeah still here lol, and thanks for the compliment, it's cool to hear from yah.!

Check your inbox.

[Lotus]

The following is some info already posted but should mentioned again for its importance, (highlighted text in particular)

It is now known that estrogens exert their end-organ effect by activating a complex intracellular mechanism. Tissues which respond to estrogen possess intracytoplasmic proteins (receptors) that preferentially bind specific steroids.

For instance, a cell from the uterus will possess 5000–15,000 estrogen receptors whereas a cell from the spleen will have none. These receptors recognize estrogens by their three dimensional and chemical characteristics and bind it with high affinity (KD =10-10), specificity, and saturability.

The estrogen molecules present in the circulation are relatively loosely bound to intravascular carrier proteins (sex-steroid-binding globulin [SBG]) (KD = 10-8) or to albumin. In excess of 95% of the estrogen in the circulation is found in the bound form. The estrogen readily diffuses across the cell membrane in its active free form due to a concentration and a binding gradient. The estrogen molecule is relatively small (molecular weight is 300) and lipophilic and probably passes through the cell membrane by simple diffusion.

Once in the cell, the estrogen is promptly bound to the intracellular (intracytoplasmic) receptor protein, which then undergoes a series of complex spatial changes prior to intranuclear transport. This nuclear transport occurs within 30–45 minutes after the target tissue is exposed to estrogen. The following system of nuclear interactions between receptor and DNA is a model that has been proposed by McCarty.3 The activated receptor–estrogen complex then nonspecifically binds to the DNA and protein of dispersed chromosomes (euchromatin) and stimulates acetylation of the histone protein.

This acetylation of the histones in nucleosomes causes the nucleosome to “open up” and expose specific DNA segments for transcription. The “estrogen message” is transcribed into new messenger RNA which then migrates back into the cytoplasm and activates various cellular processes including new protein synthesis. The now “freed” receptor protein is probably recycled back into the cytoplasm for further use.

The estrogen receptor recognizes a molecule as being “estrogen” if its size, three-dimensional configuration, and charge are similar to the parent molecule. Therefore, the nonsteroidal synthetic estrogens may not resemble the “prototype” estrogen (estradiol-17β) on paper diagrams but are very similar in shape and other properties as seen by the cellular receptor. Estrogen receptors are perhaps the determinants of potency for estrogenic substances.

The estrogen receptors preferentially bind estradiol over estriol (2x) and estrone (3x).5 This receptor also discriminates among the estrogens by binding estradiol within the cellular nucleus longer than the weaker estrogens estriol and estrone.

Therefore, estradiol is the most potent of the natural estrogens probably because of the greater affinity and duration of its receptor-binding compared with the other available estrogens. Receptors for estrogen and other steroid hormones can now be accurately quantified and studied. Estrogen in physiologic concentrations stimulates the synthesis of estrogen receptors and of progesterone and testosterone receptors.

Progesterone and testosterone, however, inhibit estrogen receptors. Progesterone inhibits its own receptor population in the secretory phase of human endometrium. Thus, it is apparent that for estrogen to bind and influence a tissue, the specific estrogen receptors must be present. The potency of a particular estrogen in a tissue roughly parallels and is probably dependent on the quantity of the estrogen receptor in the cells of that tissue. Studies with estrogen receptors in breast cancers are being successfully utilized to predict the responsiveness of these tumors to hormonal manipulation.

http://www.glowm.com/section_view/item/2.../value/237

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The adrenal gland is the primary source of estrogen in postmenopausal women, and estrone is the dominant estrogen, the E2:E1 ratio being reversed after menopause. In comparison to those of cycling women, estrone levels are reduced to low follicular phase levels. There is an insignificant contribution to the estrone pool from estradiol conversion, ovarian estrone secretion, and conversion of ovarian androstenedione

However, virtually all the total estrone production can be accounted for by peripheral conversion of androstenedione in adipose tissue and liver. There is a strong correlation with age and obesity in the conversion efficiency of androstenedione to El. The nonobese postmenopausal woman has an average androstenedione to E1 conversion rate of 2.7%, compared with 5.1% for the obese postmenopausal patient with uterine bleeding secondary to increased endogenous estrogen.

[Lotus]

One of the most glaring statements is this:

nuclear transport occurs within 30–45 minutes after the target tissue is exposed to estrogen.

[The First Aria]

Nuclear, eh?? Nice to know my boobs one day can act as a night lite.. You know, glow in the dark? OOOpps sorry. Very informative. (still scratching my head)

[Lotus]

Nuclear, eh?? Nice to know my boobs one day can act as a night lite.. You know, glow in the dark? OOOpps sorry. Very informative. (still scratching my head)

Ok lol, English please.

Yeah I get all flustered talking about the whole DNA sequence, just means that when E enters the nucleus of the receptors the binding process (growth) occurs. Sooo, if hormones are released every 90 minutes and binding takes 30-45 minutes upon activation, one should follow this process when supplementing. Like I stated elsewhere about short bursts of meds to correspond the cycle, e.g. Taking supplements every 4 hrs as opposed to the big doses.

[Lotus]

Add Gamma Linolenic Acid to the list of "5 alpha reductase inhibitors"

GLA (also found in evening primrose oil, borage seed oil, black currant oil)

Reductase by specific aliphatic unsaturated fatty acids.

Abstract
Human or rat microsomal 5 alpha-reductase activity, as measured by enzymic conversion of testosterone into 5 alpha-dihydrotestosterone or by binding of a competitive inhibitor, [3H]17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([3H]4-MA) to the reductase, is inhibited by low concentrations (less than 10 microM) of certain polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: gamma-linolenic acid greater than cis-4,7,10,13,16,19-docosahexaenoic acid = cis-6,9,12,15-octatetraenoic acid = arachidonic acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids, retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and the enzymic assay correlated well except for elaidic acid and linolelaidic acid, the trans isomers of oleic acid and linoleic acid respectively, which were much less active than their cis isomers in the binding assay but were as potent in the enzymic assay. gamma-Linolenic acid had no effect on the activities of two other rat liver microsomal enzymes: NADH:menadione reductase and glucuronosyl transferase. gamma-Linolenic acid, the most potent inhibitor tested, decreased the Vmax. and increased Km values of substrates, NADPH and testosterone, and promoted dissociation of [3H]4-MA from the microsomal reductase. gamma-Linolenic acid, but not the corresponding saturated fatty acid (stearic acid), inhibited the 5 alpha-reductase activity, but not the 17 beta-dehydrogenase activity, of human prostate cancer cells in culture. These results suggest that unsaturated fatty acids may play an important role in regulating androgen action in target cells.

http://www.ncbi.nlm.nih.gov/pubmed/1637346

________________________________

Gamma Linolenic Acid


Scientific/medical name(s): gamma linolenic acid

Description
Gamma linolenic acid (GLA) is an omega-6 unsaturated fatty acid made in the human body from linoleic acid, an essential fatty acid found in vegetable oils and egg yolks. The main supplemental sources of GLA are oils of the seeds of evening primrose, borage, and black currant plants. (For more information, see Evening Primrose.) Many companies sell these oils as good sources of GLA. It is also found in human breast milk.

Overview
Some studies have shown that GLA can slow or stop the growth of some types of cancer cells in tissue cultures in the laboratory. The same kinds of studies suggest that GLA may help some cancer drugs to work better. However, there is very little evidence as yet that GLA supplements work to prevent or treat cancer in humans. Human studies are under way to evaluate the role of GLA and other essential fatty acids on the growth of cancer.

How is it promoted for use?
Gamma linolenic acid is normally used by the body to make prostaglandins (hormone-like substances). Prostaglandins are believed to be involved in many processes in the body, including regulation of the immune system.

http://www.cancer.org/treatment/treatmen...lenic-acid


___________________________

Dosing

GAMMA LINOLENIC ACID SIDE EFFECTS & SAFETY
Gamma linolenic acid is POSSIBLY SAFE for most adults when taken by mouth in amounts of no more than 2.8 grams per day for up to a year. It can cause digestive-tract side effects, such as soft stools, diarrhea, belching, and intestinal gas. It can also make blood take longer to clot.

Special Precautions & Warnings:
Pregnancy and breast-feeding: There is not enough reliable information about the safety of taking gamma linolenic acid if you are pregnant or breast-feeding . Stay on the safe side and avoid use.

Bleeding disorders: Gamma linolenic acid might slow blood clotting. There is some concern that it might increase the risk of bruising and bleeding in people with bleeding disorders.

Surgery: Since gamma linolenic acid might slow blood clotting, there is concern that it might increase the risk of extra bleeding during and after surgery. Stop taking gamma linolenic acid at least 2 weeks before a scheduled surgery.


http://www.webmd.com/vitamins-supplements/ingredientmono-805-GAMMA%20LINOLENIC%20ACID.aspx?activeIngredientId=805&activeIngredientName=GAMMA%20LINOLENIC%20ACID

[pom19]

Lotus, tell us about Evening Primrose. Thanks, POM

[Lotus]

Lotus, tell us about Evening Primrose. Thanks, POM

Hey POM, much can be debated about GLA's, Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable healthcare provider.. I had it in the beginning of my program, honestly I can't remember why I stopped, I would reconsider upon reviewing further.


Evening Primrose Oil- massage, Fibrocystic breast pain, treats hot flashes, relieves PMS symptoms, relieves Eczema, hormone balance, fights breast tumors and diabetes. Reports have GLA-Gamma-Linolenic Acid as helping with RA and arthritis, diabetic neuropathy, ADHD and CFS (chronic fatigue syndrome). And UPDATED to include it being an inhibitor of 5 alpha-reductase, the enzyme that converts testosterone to DHT, (DHT is bad for BOOB GROWTH).


Omega-6 supplements, including GLA and EPO, should not be used if you have a seizure disorder because there have been reports of these supplements inducing seizures.

Doses of GLA greater than 3,000 mg per day should be avoided because, at that point, production of AA-Arachidonic Acid(rather than DGLA) may increase.

__________________________________

What the Science Says

There is not enough evidence to support the use of evening primrose oil for any health condition.
According to a comprehensive 2013 evaluation of the evidence, evening primrose oil, taken orally (by mouth), is not helpful for relieving symptoms of eczema.
Evening primrose oil has been studied for rheumatoid arthritis and breast pain. However, study results are mixed, and most studies have been small and not well designed.
Evening primrose oil does not appear to affect menopausal symptoms.
The best-designed clinical trials of evening primrose oil for PMS found no effect.
http://nccam.nih.gov/health/eveningprimrose


gamma-Linolenic acid

Gamma-linolenic acid or GLA (γ-Linolenic acid), (INN and USANgamolenic acid) is a fatty acid found primarily in vegetable oils. It is sold as a dietary supplement for a variety of human health problems, although there is little or no evidence of its effectiveness.[1][2][3] However when acting on GLA, 5-lipoxygenase produces no leukotrienes and the conversion by the enzyme of arachidonic acid to leukotrienes is inhibited.
http://en.m.wikipedia.org/wiki/Gamma-Linolenic_acid


Fatty acid metabolism in health and disease: the role of delta-6-desaturase.

Abstract
Linoleic acid is the main dietary essential fatty acid (EFA). To be fully utilized by the body, it must be metabolized to a range of other substances. The first step in this pathway is delta-6-desaturation to gamma-linolenic acid (GLA). This step is slow and rate-limiting, particularly in humans. If delta-6-desaturation is impaired for any reason, the supply of further metabolites may be inadequate for normal function. If the consumption of further metabolites is excessive, then a normal rate of delta-6-desaturation may be inadequate. In these circumstances the direct supply of GLA or further metabolites may be of value. This concept is illustrated by atopic eczema and diabetes, which may represent inherited and acquired examples of inadequate delta-6-desaturation.
PMID: 8386433 [PubMed - indexed for MEDLINE] Free full text
http://www.ncbi.nlm.nih.gov/pubmed/8386433
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Essential fatty acid interactions

The actions of the ω-3 (omega-3) and ω-6 (omega-6) essential fatty acids (EFAs) are best characterized by their interactions; they cannot be understood separately.

Arachidonic acid (AA) is a 20-carbon ω-6 conditionally essential fatty acid.[1] It sits at the head of the "arachidonic acid cascade" – more than 20 different signalling paths that control a wide array of bodily functions, but especially those functions involving inflammation, cell growth and the central nervous system.[2] Most AA in the human body derives from dietary linoleic acid (another essential fatty acid, 18:2 ω-6), which is derived from nuts, seeds, vegetable oils and animal fats.

In the inflammatory response, two other groups of dietary essential fatty acids form cascades that parallel and compete with the arachidonic acid cascade. EPA (20:5 ω-3) provides the most important competing cascade. It is ingested from oily fish or derived from dietary alpha-linolenic acid found in, for instance, walnuts, hemp oil and flax oil. DGLA (20:3 ω-6) provides a third, less prominent cascade. It derives from dietary GLA (18:3 ω-6) found in, e.g. borage oil. These two parallel cascades soften the inflammatory promoting effects of certain eicosanoids made from AA. Low dietary intake of these less inflammatory promoting essential fatty acids, especially the ω-3s, is correlated with a variety of inflammation-related diseases.

Today, the usual diet in industrial countries contains much less ω-3 fatty acids than the diet of a century ago and a much greater amount of pollution that evokes the inflammatory response.[when?] The diet from a century ago had much less ω-3 than the diet of early hunter-gatherers and much less pollution.[3] We can also look at the ratio of ω-3 to ω-6 in comparisons of their diets. These changes have been accompanied by increased rates of many diseases – the so-called diseases of civilization – that involve inflammatory processes. There is now very strong evidence[4] that several of these diseases are ameliorated by increasing dietary ω-3, and good evidence for many others. There is also more preliminary evidence showing that dietary ω-3 can ease symptoms in several psychiatric disorders.[5]

http://en.m.wikipedia.org/wiki/Essential...ietary_GLA

[Lotus]

If you've never heard of the KEGG pathway your in for a treat.

KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information.



   

KEGG: kyoto encyclopedia of genes and genomes

KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information. The genomic information is stored in the GENES database, which is a collection of gene catalogs for all the completely sequenced genomes and some partial genomes with up-to-date annotation of gene functions. The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle. The PATHWAY database is supplemented by a set of ortholog group tables for the information about conserved subpathways (pathway motifs), which are often encoded by positionally coupled genes on the chromosome and which are especially useful in predicting gene functions. A third database in KEGG is LIGAND for the information about chemical compounds, enzyme molecules and enzymatic reactions. KEGG provides Java graphics tools for browsing genome maps, comparing two genome maps and manipulating expression maps, as well as computational tools for sequence comparison, graph comparison and path computation. The KEGG databases are daily updated and made freely available (http://www. genome.ad.jp/kegg/).

http://www.ncbi.nlm.nih.gov/pubmed/10592173

[Lotus]

So this is the money question, and apparently science can't answer this yet,

Which metabolic pathway does Testosterone take when it comes upon the 2 enzymes, 5 alpha reductase and aromatase, keep in mind it's present in both male and females.

Metabolic pathways are said to flow all in the same direction, although that's not entirely correct, there is a backdoor. -shhh-