Hi BN,
I apologize I haven't answered some recent posts or pm's, I appreciate your time and questions, I will answer them asap. I've been taking a sabbatical (as referred by spanky, thanks) to focus on some research and other things. A current model I'm working on is deactivation of DHT in the prostate/testes to a second estrogen. I again apologize for the technical detail of this post. I do believe however given more time, patience and scientific understanding we can advance NBE to the next level. My personal opinion is we have to much fluff, e.g. meaningless dribble conversation that have nothing to do with breast growth, lol, suck it buttercup.
I do see some people advancing research, (awesome, thanks).
I do hope I don't lose any peeps along the way
. Current tools, bile acids, HSD's, Leptin (forskolin, or green tea) as a release of fat stores (adipose) and estrogen. So what's this about?, well what if I told you you can leap frog over DHT and create a second estrogen out of a metabolite of DHT, say what Lotus?.
Pass that pipe eh lmao. Pull up those saggy panties (or boots if you prefer) and put on your thinking caps, this is doable. What still needs to be addressed though is how long of a process does this take?, meaning rapid signaling? (seconds to minutes vs classical signaling? (days to weeks) which I'll address in another thread.
good luck, you'll need it.
11β-HSD stimulates cortisol which then upregulates 3 beta HSD to inactivate DHT via CYP7B1 in the prostrate, when this happens a second estrogen known as 5alpha-androstane-3beta,17beta-diol is produced. Additionally, DHEA (25-50mg?) should further upregulate more E1/E2 because of the inactivation of DHT. DHT has no effect on 3 beta HSD in the prostrate, I believe this holds true for the testes, which means it's unopposed (aka-green light for estrogen production in the testes). Leptin regulates abdominal fats which if utilized releases a cascade of stored estrogen.
![[Image: attachment.php?aid=10856]](http://www.breastnexus.com/attachment.php?aid=10856)
(Highlighted points from 1st study) 11beta-hydroxysteroid dehydrogenase (HSD1), the enzyme responsible for the conversion of cortisone into cortisol and the P450 aromatase, the enzyme catalysing androgens aromatization into estrogens, are both expressed in human adipose tissue. Leptin up-regulates the HSD1 (2.4-fold) and the P450 aromatase (1.6-fold) mRNA expression in men preadipocytes. In women preadipocytes, 17beta-estradiol strongly stimulates HSD1 mRNA expression (10-fold) and, in contrast, decreases by half the P450 aromatase expression. In men, 17beta-estradiol has no influence on HSD1 expression but up-regulates P450 aromatase mRNA expression (2.4-fold)
Sex steroids and leptin regulate 11β-hydroxysteroid dehydrogenase I and P450 aromatase expressions in human preadipocytes: Sex specificities
Service de Biochimie et de Biologie Moléculaire, UPRES EA 2493, Faculté de Médecine Paris-Ile de France-Ouest, Université Versailles St Quentin, Centre Hospitalier de Poissy, 78303 Poissy Cedex, France.
The Journal of Steroid Biochemistry and Molecular Biology (Impact Factor: 3.63). 07/2006; 99(4-5):189-96. DOI: 10.1016/j.jsbmb.2006.01.007
Source: PubMed
ABSTRACT
Adipose tissue is an important site of steroid hormone biosynthesis, as type I 11beta-hydroxysteroid dehydrogenase (HSD1), the enzyme responsible for the conversion of cortisone into cortisol and the P450 aromatase, the enzyme catalysing androgens aromatization into estrogens, are both expressed in human adipose tissue. In the present report, we have investigated the possibility that sex steroids and leptin could regulate these two enzymes in cultured preadipocytes from men and women intra-abdominal fat depots. In women preadipocytes, human recombinant leptin down-regulates HSD1 mRNA expression (-58%) and P450 aromatase activity (-26%). Conversely, leptin up-regulates the HSD1 (2.4-fold) and the P450 aromatase (1.6-fold) mRNA expression in men preadipocytes. In women preadipocytes, 17beta-estradiol strongly stimulates HSD1 mRNA expression (10-fold) and, in contrast, decreases by half the P450 aromatase expression. In men, 17beta-estradiol has no influence on HSD1 expression but up-regulates P450 aromatase mRNA expression (2.4-fold). Finally, androgens increase by a factor of 2.5-5 the mRNA expression of both enzymes in men. These findings suggest that sex steroids and leptin either increase or decrease local cortisol and estrogens productions in men or in women preadipocytes, respectively. They also indicate that steroid metabolism in adipose tissue is controlled by a coordinated regulation of P450 aromatase and HSD1 expressions. Finally, the important sex-specific differences described herein may also contribute to explain the sexual dimorphism of body fat distribution in humans.
Anticancer Res. 1995 Jul-Aug;15(4):1349-54.
Inhibition of 3 beta-hydroxysteroid-dehydrogenase: an approach for prostate cancer treatment?
Geldof AA1, Dijkstra I, Newling DW, Rao BR.
Author information
Abstract
Over 80% of clinically manifested prostate cancers respond to androgen withdrawal. Several alternatives to castration have been explored. Since a growth promoting role for androstenedione has been suggested, we investigated the effect of inhibition of 3 beta-hydroxy-steroid-dehydrogenase (3 beta-HSD), a key enzyme involved in the biosynthesis of practically all steroids. In a previous study a reduced proliferation rate of androgen responsive R3327-H tumor was demonstrated after in vivo treatment with 17 beta-N,N-diethylcarbamoyl-4-aza-5 alpha-androstan-3-one (4MA) - a putative 5 alpha-reductase inhibitor. In the present investigation 3 beta-HSD enzyme activity derived from human placenta, testis and ovarian cancer cell line and from rat testis was determined using radiolabeled dehydroepiandrosterone (DHEA) or pregnenolone. Among different synthetic compounds known to interfere with steroidogenesis, only 4MA was shown to potently inhibit in vitro 3 beta-HSD activity from all tissue sources. 4MA was administered to male Copenhagen rats bearing R3327-H androgen dependent prostate tumors and levels of different androgens in serum and prostate tumor were measured using reversed phase HPLC and radioimmunoassay. The decreased content of androstenedione in serum and tumor tissue with DHEA accumulation in prostate tumor tissue showed an effective 3 beta-HSD inhibition by 4MA occurring in vivo as well. These observations unequivocally demonstrate a 3 beta-HSD inhibiting effect of 4MA in vitro as well as in vivo and point to a role for androstenedione in the promotion of cell proliferation in androgen sensitive tumors. 3 beta-HSD dependent androstenedione production could thus constitute a proper target -eventually combined with other endocrine treatment - for the treatment of hormone dependent prostate cancer.
PMID: 7654020 [PubMed - indexed for MEDLINE]
An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth.
Weihua Z1, Lathe R, Warner M, Gustafsson JA.
Author information
Erratum in
* Proc Natl Acad Sci U S A. 2006 May 23;103(21):8298.
Abstract
Epithelial proliferation of the ventral prostate in rodents peaks between 2 and 4 weeks of age, and by week 8, proliferating cells are rare. We have used ERbeta(-/-) and CYP7B1(-/-) mice to investigate the role of ERbeta and one of its ligands, 5alpha-androstane-3beta,17beta-diol (3betaAdiol), in growth of the ventral prostate. Before puberty, ERbeta was found in quiescent but not in proliferating cells, and proliferating cells occurred more frequently in ventral prostates of ERbeta(-/-) mice than in wild-type littermates. Treatment with 3betaAdiol decreased proliferation in wild-type but not in ERbeta(-/-) mice. In rats, treatment with 3betaAdiol from postnatal day 2 to 28 resulted in reduction in growth of ventral prostates. The prostates of CYP7B1(-/-) mice were hypoproliferative before puberty and smaller than those of their wild-type littermates after puberty. Because CYP7B1 represents the major pathway for inactivating 3betaAdiol in the prostate, we suggest that ERbeta, 3betaAdiol, and CYP7B1 are the components of a pathway that regulates growth of the rodent ventral prostate. In this pathway, ERbeta is an antiproliferative receptor, 3betaAdiol is an ERbeta ligand, and CYP7B1 is the enzyme that regulates ERbeta function by regulating the level of 3betaAdiol.
PMID: 12370428 [PubMed - indexed for MEDLINE] PMCID: PMC129718 Free PMC Article
http://onlinelibrary.wiley.com/store/10.1111/j.1365-2826.2009.01840.x/asset/j.1365-2826.2009.01840.x.pdf?v=1&t=ihqy2cca&s=c3f1dd59bccf48afe2375bb5d767a1b09d8e302c&systemMessage=Wiley+Online+Library+will+have+be+unavailable+on+Saturday+5th+December+from+10%3A00-14%3A00+GMT+%2F+05%3A00-09%3A00+EST+%2F+18%3A00-22%3A00+SGT+for+essential+maintenance.+Apologies+for+the+inconvenience.
Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like effects, in modulating the aquaporin-9 expression in the rat efferent ductules
http://www.ncbi.nlm.nih.gov/pmc/articles...7-4-51.pdf
Estrogen receptor beta in the brain: From form to function
Estrogens have numerous effects on the brain, both in adulthood and during development. These actions of estrogen are mediated by two distinct estrogen receptor (ER) systems, ER alpha (ERα) and ER beta (ERβ). In brain, ERα plays a critical role in regulating reproductive neuroendocrine function and behavior, however, a definitive role for ERβ in any neurobiological function has been slow in forthcoming. Clues to the function of ERβ in the central nervous system can be gleaned from the neuroanatomical distribution of ERβ and the phenotypes of neurons that express ERβ. ERβ immunoreactivity has been found in populations of GnRH, CRH, vasopressin, oxytocin and prolactin containing neurons in the hypothalamus. Utilizing subtype-selective estrogen receptor agonists can help determine the roles for ERβ in non-reproductive behaviors in rat models. ERβ-selective agonists exert potent anxiolytic activity when animals were tested in a number of behavioral paradigms. Consistent with this, ERβ-selective agonists also inhibited the ACTH and corticosterone response to stress. In contrast, ERα selective agonists were found to be anxiogenic and correspondingly increased the hormonal stress response. Taken together, our studies implicate ERβ as an important modulator of some non-reproductive neurobiological systems. The molecular and neuroanatomical targets of estrogen that are mediated by ERβ remain to be determined. A number of splice variants of ERβ mRNA have been reported in brain tissue. Imaging of eGFP labeled chimeric receptor proteins transfected into cell lines shows that ERβ splice variation can alter trafficking patterns and function. The originally described ERβ (herein termed ERβ1) is characterized by possessing a high affinity for estradiol. Similar to ERα, it is localized in the nucleus and is trafficked to nuclear sites termed ''hyperspeckles'' following ligand binding. In contrast, ERβ2 contains an 18 amino acid insert within the ligand-binding domain and as a result can be best described as a low affinity form of ERβ. A delta3 (δ3) variant of ERβ has a deletion of the 3rd exon (coding for the second half of the DNA-binding domain) and as a result does not bind an estrogen response element in DNA. δ3 variants are trafficked to a unique low abundance and larger nuclear site following ligand binding. A delta4 (δ4) variant lacks exon 4 and as a result is localized to the cytoplasm. The amount of individual splice variant mRNAs varies depending upon brain region. Examination of neuropeptide promoter regulation by ERβ splice variants demonstrates that ERβ functions as a constitutively active transcription factor. Moreover, it appears that splice variation of ERβ alters its ability to regulate transcription in a promoter-dependent and ligand-dependent fashion.
Curr Med Chem. 2007;14(27):2918-24.
Estrogens and glucocorticoid hormones in adipose tissue metabolism.
Mattsson C1, Olsson T.
Author information
Abstract
Women have a higher percentage of body fat than men, and there is a gender-specific difference in fat distribution: Females tend to accumulate fat around the hips, buttocks, and thighs while men have a larger intra-abdominal (visceral) fat mass. After menopause, there is a redistribution of fat depots, and post-menopausal women develop increased amounts of visceral fat. The risk of developing obesity-related diseases is significantly lower in pre-menopausal women compared to men, a difference that is abolished after menopause, suggesting that the female sex steroid estrogen influences adipogenesis and adipose metabolism. Experimentally, estrogen increases the size and number of subcutaneous adipocytes and attenuates lipolysis. Post-menopausal women also develop a more atherogenic lipid pattern and decreased levels of the prothrombotic protein plasminogen activator inhibitor-1, which attenuates fibrinolysis. Pathologically increased circulating cortisol concentration is associated with dysmetabolic features e.g., central obesity, elevated blood pressure, insulin resistance, and dyslipidemia. In "simple obesity," glucocorticoid production is elevated. Peak levels of circulating cortisol are however low or normal, possibly because of increased clearance and/or tissue-specific changes in cortisol production. In addition to the adrenal production of cortisol, cortisol is also generated in adipose tissue by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) which converts inactive cortisone to active cortisol. The enzyme activity in subcutaneous fat increases with increasing body weight. Estrogen seems to have a tissue-specific influence on 11betaHSD1 enzyme activity, attenuating it in liver, kidney, and testis but upregulating 11betaHSD1 mRNA expression in preadipocytes from women. In the present review, we summarize and discuss the interaction between glucocorticoids and sex steroids and their influence on adipocyte metabolism.
PMID: 18045137 [PubMed - indexed for MEDLINE]
hydroxylase, bile acid 6β-hydroxylase, and growth hormone-responsive steroid hormone hydroxylases.
Waxman DJ1.
Author information
Abstract
The hydroxylation of cholesterol, bile acids, and steroid hormones by liver cytochrome P450 (CYP) enzymes proceeds with a high degree of regiospecificity, and contributes to both biosynthetic and catabolic pathways of sterol metabolism. CYP 7-catalyzed cholesterol 7α-hydroxylation, a key control point of bile acid biosynthesis, is regulated at a pretranslational step, probably transcription initiation, by multiple factors, including liver bile acid and cholesterol levels, thyroid hormone status, and diurnal rhythm. Hydrophobic bile acids, such as lithocholic acid, are converted to less cholestatic derivatives by 6β-hydroxylation carried out by CYP 3A P450s, which also catalyze steroid hormone 6β-hydroxylation reactions. Complex, gender-dependent developmental patterns characterize the expression of steroid 5α-reductase and several rat liver steroid hydroxylase CYPs. Multiple pituitary-dependent factors regulate the expression of these enzymes; of greatest importance are the gonadal steroids and the sex-dependent secretory patterns of growth hormone (GH) that they impart. The continuous presence of GH in circulation, a characteristic of adult female rats, positively regulates expression of the female-specific steroid disulfate 15β-hydroxylase CYP 2C12, while expression of the male-specific steroid 16α- and 2α-hydroxylase CYP 2C11 is stimulated by the intermittent pituitary secretion of GH that occurs in adult male rats. Intermittent GH can stimulate CYP 2C11 gene expression even when the hormone presents to the hepatocyte at a non-physiological pulse amplitude, duration, and frequency, provided that an interpulse interval of no GH (obligatory recovery period) is maintained for at least 2.5 h. GH regulates the expression of the CYP 2C11 and CYP 2C12 genes at the level of transcription initiation. This process is probably mediated by sex-dependent and GH-regulated protein-DNA interactions, such as those observed in the 5'-flank of the CYP 2C12 gene. Thyroid hormone is a second major regulator of liver steroid hydroxylase P450 activity. It regulates these enzymes directly, at a pretranslational step, and indirectly, through its stimulation of pituitary GH secretion and by its positive effects on the expression of the flavoenzyme NADPH-P450 reductase, which catalyzes electron transfer that is obligatory for all microsomal steroid hydroxylation reactions.
Copyright © 1992. Published by Elsevier Ltd.
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I value your research! ( . Y . ) hehe