1.
Sources and Structure
1.1
Sources
7-Keto DHEA (henceforth 7-keto) is a molecule derived from DHEA (3β-Hydroxy-5-Androstene-17-one). 7-keto is synonymous with 7-oxo or 7-oxo DHEA as the ketone group added contains any oxygen molecule; 7-keto is more commonly used but is a brand name, while 7-oxo is the technically accurate name.[1] 7-keto is naturally occurring (as DHEA is naturally occurring and the enzymes that mediate the conversion present in the human body) at a highly variable level of 0.280+/-0.227nmol/L in serum with undetectable levels in some persons,[2] with this one study failing to note any differences between gender or age after 25[2] (DHEA itself is known to decline with age).
Supplementation of 7-keto is sometimes used with the acetyl ester, known fully as 3β-Acetyl-7-ketoDHEA.[3] Supplementation of 7-keto is sometimes used in place of supplementation of DHEA if the androgenic and estrogenic effects of DHEA are not desired, as 7-keto is incapable of converting to these active steroid hormones.
An endogenously produced metabolite of DHEA that appears to be more involved with corticosterone metabolism and is not inhernetly a steroid precursor like DHEA is
1.2
Structure and Properties
7-oxygenated metabolites appeared to be prone to dehydration ex vivo.[4]
2.
Pharmacology
2.1
Serum
The acetylated form of 7-keto (3β-acetyl-7-oxo-DHEA) appears to be rapidly metabolized to a sulfated form of 7-keto (7-ketoDHEA 3βsulfate[5]) with free 7-ketoDHEA as an intermediate, as the acetate group and the sulfate group occur on the same carbon.[3] Sulfation or acetylation of 7-keto at the 3-position does not appear to interfere with the induction of fat burning enzymes (mentioned in section on fat mass and obesity).[6]
7-ketoDHEA, similar to DHEA, can exist in a free form or a sulfated form in the body
2.2
Metabolism
7-keto DHEA is one of many metabolites of Dehydroepiandrosterone (DHEA),[7] where DHEA is converted into 7α-hydroxyDHEA (Oxysterol 7α-hydroxylase,[8] CYP3A4/5,[9] or CYP7B1[8][10]) and then can be converted into 7β-hydroxyDHEA via 11β-HSD type 1[11][12] and this conversion can occurs in a wide variety of tissues including the brain, spleen, thymus, perianal skin, ventral skin, intestine, colon, coecum and skeletal muscle.[13][14][15] 11β-HSD type 1 can then convert either 7α or 7β hydroxyDHEA into 7-oxo-DHEA (synonymous with 7-keto).[16][17] Due to the irreversibility of the Oxysterol 7α-hydroxylase and CYP3A4/5 enzymes, there is no conversion of these three molecules back into parent DHEA, and the metabolism of DHEA into androgenic or estrogenic precursors (into androstenedione via 3β-HSD) cannot occur following 7-keto supplementation.[15]
The activity of 11β-HSD1 balances the oxygenated DHEA metabolites between one another[18] and the enzyme known as Hexose-6-phosphate dehydrogenase appears to influence favorably conversion of these oxygenated metabolites into 7β hydroxyDHEA.[19]
7-keto is one of three 'oxygenated DHEA metabolites', and cannot be converted into DHEA after supplementation due to the conversion of DHEA into these oxygenated metabolites occurring in only one direction rather than a multidirectional function (A -> B only, rather than A being interchangeable with B)
2.3
Topical Application
7-keto appears to be biologically active when administered as a topical cream at the dosage of 25mg.[20]
3.
Neurology
3.1
Memory and Cognition
Injections of either DHEA (20mg/kg) or 7-keto (24mg/kg) in mice who were also injected with the learning neurotoxin scopolamine noted that both treatments noted that both neurosteroids were able to abolish the learning impairment induced by scopolamine in young mice, and that young mice given either neurohormone without scopolamine appeared to outperform control mice in memory acquisition training but this trend was not statistically significant.[21] In older mice given 7-keto without scopolamine, there were improvements in memory retention that were not seen with parent DHEA[21] (benefit has been noted with DHEA when injected directly into the brains of older mice[22][23][24])
Preliminary evidence that 7-keto can reduce memory impairment by cholinergic toxins or by age, but the studies are currently using injections with no human evidence
3.2
Fatigue
One study using 200mg 7-keto for 8 weeks in combination with a calorically restricted diet and exercise program (both adminstered to placebo) failed to find any significant difference in post-intervention ratings of fatigue or vigor (assessed via Profile of Mood States).[25]
Currently no evidence to support a reduction in fatigue associated with 7-keto supplementation
3.3
PMS
When assessing neurohormones of women during the midfollicular and midluteal phases of their menstrual cycles, it was noted that despite no changes in parent DHEA that there was a lower circulating level of oxygenated metabolites including 7-keto; the authors hypothesized that oxygenated DHEA metabolites may play a role in mood changes associated with menopause.[26]
Endogenous 7-keto and the oxygenated DHEA metabolite appear to be reduced in the brain during a menstrual cycle, and are thought to be related to mood changes (as they are neurohormones). There are currently no studies using supplementation to assess this claim
3.4
Alcoholism
In rats conditioned to respond to alcohol ingestion (operant conditioning), acute consumption of 7-keto (10-56mg/kg) was able to reduce responding to alcohol, suggesting of possible anti-alcoholic effects; these effects were also noted with DHEA (10-180mg/kg).[27] 7-keto DHEA and DHEA itself were equally efficacious in reducing blood alcohol (in a dose dependent manner) while 7-keto was more effective at reducing response to a near absolute degree at 56mg/kg;[27] the authors noted that this may not have been an inherent effect (as DHEA is known to not alter alcohol metabolism[28]) and is likely indicative of less alcohol consumption in the rats.[27]
7-keto appears to have a fair bit of animal evidence to support its usage as an anti-alcohol consumption agent, and has more potency than parent DHEA. Fairly potent in animal studies and awaiting human trials
3.5
Stress
One letter to the editor[29] notes 5 case reports where severe trauma (stemming from childhood abuse) noted that in these treatment resistant women supplementation of 7-keto was associated with rapid improvements in vocational and interpersonal functioning and subjective improvements after 25-50mg for 4-6 weeks (in one case a dose of 75mg was used).[29]
A few case studies reporting that 7-keto can improve stress in trauma patients, no trials conducted
4.
Cardiovascular Health
4.1
Blood Pressure
Despite being associated with greater weight loss than placebo, one study using 200mg 7-Keto for 8 weeks in obese persons failed to find any significant influence on systolic or diastolic blood pressure at rest.[25]
Not enough evidence to assess the interaction of 7-keto DHEA and blood pressure
5.
Fat Mass and Obesity
5.1
Mechanisms
Higher (non-supplemental) circulating levels of Oxygenated derivatives of DHEA have been correlated with less obesity in vivo in males but not females, and is thought to be associated with the state of less body fat.[30]
In regards to activation of 'thermogenic enzymes' (mitochondrial sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme, their induction decreasing efficiency of the TCA cycle and acts as an uncoupling agent[6][31][32]) 7-keto as well as the similar structures 7α-hydroxyDHEA and 7β-hydroxyDHEA are all active, although 7-keto moreso; DHEA per se is ineffective.[6] Induction of these enzymes appears to reduce mitochondrial membrane potential and increase substrate oxidation rates, which appears to be similar to thyroid hormones in action.[33]
One study feeding rats 7-keto at 0.2% of feed for 6-9 days noted that the rates for liver mitochondrial enzymes were increased for sn-glycerol-3-phosphate dehydrogenase (569%) and the protein content increased for malic enzyme (859%), sn-glycerol-3-phosphate dehydrogenase (137%), fatty acid acetyl-CoA oxidase (128%), and catalase (66.8%).[33]
7-keto appears to induce enzymes associated with mitochondrial membrane permeability, increasing permeability and secondary to that exerting an uncoupling effect where more substrate must be oxidized to meet cellular ATP quota
5.2
Interventions
One study using 7-Keto in isolation at 200mg (100mg twice a day for 7 days) noted that, during a period of caloric restriction (800kcal less than regular intake), metabolic rate increased an average of 1.4% (total caloric expenditure a highly variable 21+/-115kcal) while placebo experienced a decrease in metabolic rate by 3.9% relative to baseline; this study was too short in duration to assess changes in weight.[34]
In accessing the metabolic rate, 7-Keto supplementation appears to attenuate or reverse the decline in metabolic rate associated with caloric restriction
Studies conducted over a longer period of time note that 200mg (100mg twice daily) for 8 weeks in obese adults in combination with a weight loss diet (1800kcal mixed diet) and exercise program (3 days weeks cross training) noted that the loss in weight associated with placebo (0.97kg) was increased (2.88kg) as well as the fat loss (from 0.57% to 1.8%); no significant differences in dietary intake were reported.[25]
Studies measuring weight loss associated with 7-keto note that supplementation results in more weight and fat loss over a period of time; both studies were paired with diet and exercise which may be prerequisites
Another trial (external funding source and confounded with Asparagus racemosus, choline, inositol, L-Tyrosine and minerals) noted that pairing 400mg 7-Keto (200mg twice daily) with a calorically restricted diet (25kcal/kg of target body weight) and exercise program for 8 weeks noted similar effects (increasing weight loss from 0.72+/-2.12kg in placebo to 2.15+/-2.38kg; high variability seemed to be due to exercise/diet intervention rather than supplementation as it occurred in placebo).[35]
One study using 7-keto at 200mg (alongside green tea catechins, chromium, Vitamin D, Vitamin C and calcium) during a period of caloric restriction in obese adults noted that the supplement was associated with a 3.4% increase in metabolic rate (59+/-118kcal) while placebo decreased 3.4%.[34] One study suggests a spike n 7.2% of the metabolic rate, but this study used a subactive dose of 7-Keto (17mg) paired with a variety of stimulatory compounds (Yerba Mate at 167mg, piper nigrum at 1.7mg, 50mg Coleus Forskohlii, 100mg Citris Aurantium at 6% Synephrine, and 233mg Guarana at 22% caffeine).[36]
Some studies suggest higher spikes in metabolic rate but are confounded with inclusion of other nutrients and not very respective of the bioactivity of 7-keto in isolation
6.
Interactions with Aesthetics
6.1
Hair
Hair follicle related cells have been noted to possess CYP7B1, although 11β-HSD1 was not detected.[10]
7.
Interactions with Hormones
7.1
Cortisol
7-keto and the oxygenated DHEA metabolites interconvert using some of the enzymes used in cortisol metabolism (11β-HSD1,[10] which also reduces cortisone into cortisol[37][38]). It is thought that interconversion of the two hydroxylated metabolites of DHEA via this enzyme competitively inhibit cortisone, and prevent the production of cortisol from cortisone.[39] This competitive inhibition has been noted at the concentration of 5-10µM with the β isomer being 7-fold more potent than the α isomer and 7-keto also being effective with a Ki of 1.13+/-0.15µM[10] and has elsewhere noted concentration-dependent inhibition on this enzyme[40] and may interfere with corticosterone as well as cortisone.[18] Depending on the context of the situation, the oxygenated DHEA metabolite are both substrate and inhibitors of this enzyme.[41]
At least one study has suggested that this effect may only have a role in a state of poor health,[18]
This inhibition appears to be mutual, with higher concentrations of glucocorticoids inhibiting the interconversion of oxygenated DHEA metabolites,[42] and when assessing 7α-hydroxyDHEA and the β isomer, they do not appear to directly interfere with the cortisol receptor or its activation, similar to parent DHEA.[43]
Mechanistically, 7-keto may prevent the conversion of cortisone into cortisol by competitively interfering with the enzyme that mediates the conversion
Application of 25mg 7-keto via a cream for 8 days has failed to significantly modify circulating cortisol levels over 100 days of assessment in otherwise healthy male volunteers.[20]
Despite the above mechanisms, not enough evidence assessing the levels of circulating cortisol following 7-keto supplementation
7.2
Androgens
When looking at the androgen receptor, all three oxygenated metabolites of DHEA show little efficacy in activating the androgen receptor.[44]
Application of 7-keto topical cream prior to sleep (conferring 25mg 7-keto via 5g emulgel) in 21 otherwise healthy males for 8 days has noted reductions in circulating testosterone sporadically on days 2, 23, 37, and 72 (with no significant differences on days 5-16 nor 51).[20] Throughout this study, there were no significant increases in epitestosterone until day 23 where epitestosterone remained elevated until day 100 when the study ended (with peak values after 6 weeks, reaching 55% higher than baseline).[20]
One study has failed to find any influence on testosterone levels in otherwise healthy obese adults using 200mg 7-Keto for 8 weeks, but only measured 6 individuals.[25]
No direct androgenic effects associated with 7-keto, the influence on circulating androgens appears unreliable based on limited evidence
7.3
Estrogen
When tested in vitro, 7-keto appears to activate the beta subset of the estrogen receptor (ERβ) with an EC50 around 500μM which is partially blocked by exemestane (aromatase inhibitor or AI); there was no apparent activity on the classical subset (ERα) and parent DHEA and DHEAS were eqipotent.[45] As activity was hindered with an AI and there was efficacy in HepG2 cells but not Hep293 (expressing[46] and not expressing[47] aromatase, respectively) it is though that 7-oxo can be metabolized into an estrogen.[45]
Application of 25mg 7-keto via a topical cream for 8 days has failed to note any decreases in serum estradiol during treatment, although a decrease in estraiol was noted on days 72 and 100 (reaching 48% of baseline value) which coincided with decreases in serum SHBG.[20] 200mg of 7-keto for 8 weeks in otherwise obese persons in combination with exercise and a calorically restricted diet failed to significantly influenced estradiol levels in serum (this study only measured serum estradiol of 6 persons).[25]
May directly influence estrogen receptors, but only the beta subunit (not associated with classical effects of estrogen) and is quite weak at doing so; influences on circulating estrogen level is either a reduction or no effect but there is minimal evidence looking at this interaction
7.5
Sex Hormone Binding Globulin
Sex Hormone Binding Globulin (SHBG) is a globulin that binds to and inactives both estrogen and testosterone, and has a role in regulating steroid metabolism in vivo.[48]
Sex-Hormone Binding Globulin also decreased in the latter portion of the experiment (day 51, 72, and 100) despite no significant influence during treatment.[20]
7.6
Thyroid Hormones
7-Keto at 25mg daily has been shown to increase circulating Thyroid stimulating hormone (TSH) and both active thyroid hormones (T3 and T4) 5-9 days following topical application of 7-keto cream, with effects lasting for up to 2 weeks after cessation.[1] There was high inter-individual differences seen, with youth having greater circulating levels.
One study using 8 weeks of supplementation of 200mg 7-Keto noted that supplementation was associated with an increase in T3 by 17.88ng/dL while placebo increased T3 by 2.75ng/dL while both T4 and TSH were unaffected after 8 weeks.[25]
7-keto supplementation may have a small enhancement on thyroid hormones
7.7
Gonadotropins
Application of 25mg 7-keto via cream for 8 days in otherwise healthy males has been associated with a reduction in Luteinizing Hormone (LH) by 46% and Follicle Stimulating Hormone (FSH) by 25% when measured the day after the cream was starting to be appled, but were not reliably reduced in 100 days of followup (with a slight increase in FSH on day 100).[20]
8.
Safety and Toxicology
7-Keto does not appear to be associated with side-effects at up to doses of 200mg daily for 4 weeks in otherwise healthy young males.[3]
References
- ^Hampl R, Sulcová J, Bílek R, Hill MHow short-term transdermal treatment of men with 7-oxo-dehydroepiandrosterone influence thyroid functionPhysiol Res.(2006)
- ^Kazihnitková H, Zamrazilová L, Hill M, Lapcík O, Pouzar V, Hampl RA novel radioimmunoassay of 7-oxo-DHEA and its physiological levelsSteroids.(2007 Apr)
- ^Davidson M, Marwah A, Sawchuk RJ, Maki K, Marwah P, Weeks C, Lardy HSafety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteersClin Invest Med.(2000 Oct)
- ^Ergosteroids VII: perchloric acid-induced transformations of 7-oxygenated steroids and their bio-analytical applications—a liquid chromatographic-mass spectrometric study
- ^Marwah A, Marwah P, Lardy HDevelopment and validation of a high-performance liquid chromatography assay for the quantitative determination of 7-oxo-dehydroepiandrosterone-3beta-sulfate in human plasmaJ Chromatogr B Biomed Sci Appl.(1999 Jan 22)
- ^Lardy H, Kneer N, Wei Y, Partridge B, Marwah PErgosteroids. II: Biologically active metabolites and synthetic derivatives of dehydroepiandrosteroneSteroids.(1998 Mar)
- ^Rijk JC, Bovee TF, Peijnenburg AA, Groot MJ, Rietjens IM, Nielen MWBovine liver slices: A multifunctional in vitro model to study the prohormone dehydroepiandrosterone (DHEA)Toxicol In Vitro.(2012 Sep)
- ^Wu Z, Martin KO, Javitt NB, Chiang JYStructure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1J Lipid Res.(1999 Dec)
- ^Fitzpatrick JL, Ripp SL, Smith NB, Pierce WM Jr, Prough RAMetabolism of DHEA by cytochromes P450 in rat and human liver microsomal fractionsArch Biochem Biophys.(2001 May 15)
- ^Hennebert O, Chalbot S, Alran S, Morfin RDehydroepiandrosterone 7alpha-hydroxylation in human tissues: possible interference with type 1 11beta-hydroxysteroid dehydrogenase-mediated processesJ Steroid Biochem Mol Biol.(2007 May)
- ^Le Mée S, Hennebert O, Ferrec C, Wülfert E, Morfin R7beta-Hydroxy-epiandrosterone-mediated regulation of the prostaglandin synthesis pathway in human peripheral blood monocytesSteroids.(2008 Oct)
- ^Traish AM, Kang HP, Saad F, Guay ATDehydroepiandrosterone (DHEA)--a precursor steroid or an active hormone in human physiologyJ Sex Med.(2011 Nov)
- ^El Kihel LOxidative metabolism of dehydroepiandrosterone (DHEA) and biologically active oxygenated metabolites of DHEA and epiandrosterone (EpiA)--recent reportsSteroids.(2012 Jan)
- ^Morfin R, Courchay GPregnenolone and dehydroepiandrosterone as precursors of native 7-hydroxylated metabolites which increase the immune response in miceJ Steroid Biochem Mol Biol.(1994 Jul)
- ^Lund-Pero M, Jeppson B, Arneklo-Nobin B, Sjögren HO, Holmgren K, Pero RWNon-specific steroidal esterase activity and distribution in human and other mammalian tissuesClin Chim Acta.(1994 Jan 14)
- ^Glucocorticoids inhibit interconversion of 7-hydroxy and 7-oxo metabolites of dehydroepiandrosterone: a role for 11β-hydroxysteroid dehydrogenases?
- ^Robinzon B, Prough RAInteractions between dehydroepiandrosterone and glucocorticoid metabolism in pig kidney: nuclear and microsomal 11beta-hydroxysteroid dehydrogenasesArch Biochem Biophys.(2005 Oct 1)
- ^Mitić T, Shave S, Semjones N, McNae I, Cobice DF, Lavery GG, Webster SP, Hadoke PW, Walker BR, Andrew R11β-Hydroxysteroid Dehydrogenase type 1 contributes to the Balance Between 7-Keto- and 7-Hydroxy-Oxysterols in vivoBiochem Pharmacol.(2013 Feb 13)
- ^Nashev LG, Chandsawangbhuwana C, Balazs Z, Atanasov AG, Dick B, Frey FJ, Baker ME, Odermatt AHexose-6-phosphate dehydrogenase modulates 11beta-hydroxysteroid dehydrogenase type 1-dependent metabolism of 7-keto- and 7beta-hydroxy-neurosteroidsPLoS One.(2007 Jun 27)
- ^Sulcová J, Hampl R, Hill M, Stárka L, Novácek ADelayed effects of short-term transdermal application of 7-oxo-dehydroepiandrosterone on its metabolites, some hormonal steroids and relevant proteohormones in healthy male volunteersClin Chem Lab Med.(2005)
- ^Shi J, Schulze S, Lardy HAThe effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 miceSteroids.(2000 Mar)
- ^Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it
- ^Flood JF, Smith GE, Roberts EDehydroepiandrosterone and its sulfate enhance memory retention in miceBrain Res.(1988 May 3)
- ^Flood JF, Roberts EDehydroepiandrosterone sulfate improves memory in aging miceBrain Res.(1988 May 10)
- ^A randomized, double-blind, placebo-controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults
- ^Duskova M, Simunkova K, Hill M, Starka L7-hydroxylated derivatives of dehydroepiandrosterone as possibly related to menstrual mood change in healthy womenEndocr Regul.(2011 Jul)
- ^Amato RJ, Hulin MW, Winsauer PJA comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple scheduleBehav Pharmacol.(2012 Jun)
- ^Melchior CL, Ritzmann RFDehydroepiandrosterone enhances the hypnotic and hypothermic effects of ethanol and pentobarbitalPharmacol Biochem Behav.(1992 Sep)
- ^Sageman S, Brown RP3-acetyl-7-oxo-dehydroepiandrosterone for healing treatment-resistant posttraumatic stress disorder in women: 5 case reportsJ Clin Psychiatry.(2006 Mar)
- ^Sedláčková B, Dušátková L, Zamrazilová H, Matucha P, Bičíková M, Stárka L7-oxygenated derivatives of dehydroepiandrosterone and obesityPrague Med Rep.(2012)
- ^Bobyleva V, Kneer N, Bellei M, Battelli D, Lardy HAConcerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosteroneJ Bioenerg Biomembr.(1993 Jun)
- ^Lardy H, Kneer N, Bellei M, Bobyleva VInduction of thermogenic enzymes by DHEA and its metabolitesAnn N Y Acad Sci.(1995 Dec 29)
- ^Bobyleva V, Bellei M, Kneer N, Lardy HThe effects of the ergosteroid 7-oxo-dehydroepiandrosterone on mitochondrial membrane potential: possible relationship to thermogenesisArch Biochem Biophys.(1997 May 1)
- ^Zenk JL, Frestedt JL, Kuskowski MAHUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adultsJ Nutr Biochem.(2007 Sep)
- ^The effect of 7-Keto Naturalean™ on weight loss: A randomized, double-blind, placebo-controlled trial
- ^Zenk JL, Leikam SA, Kassen LJ, Kuskowski MAEffect of lean system 7 on metabolic rate and body compositionNutrition.(2005 Feb)
- ^Agarwal AKCortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid dehydrogenase type I enzyme and reduced co-factor NADPHEndocr Res.(2003 Nov)
- ^Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid responseEndocr Rev.(2004 Oct)
- ^Muller C, Pompon D, Urban P, Morfin RInter-conversion of 7alpha- and 7beta-hydroxy-dehydroepiandrosterone by the human 11beta-hydroxysteroid dehydrogenase type 1J Steroid Biochem Mol Biol.(2006 Jun)
- ^Balázs Z, Nashev LG, Chandsawangbhuwana C, Baker ME, Odermatt AHexose-6-phosphate dehydrogenase modulates the effect of inhibitors and alternative substrates of 11beta-hydroxysteroid dehydrogenase 1Mol Cell Endocrinol.(2009 Mar 25)
- ^Hennebert O, Pernelle C, Ferroud C, Morfin R7alpha- and 7beta-hydroxy-epiandrosterone as substrates and inhibitors for the human 11beta-hydroxysteroid dehydrogenase type 1J Steroid Biochem Mol Biol.(2007 Jun-Jul)
- ^Robinzon B, Michael KK, Ripp SL, Winters SJ, Prough RAGlucocorticoids inhibit interconversion of 7-hydroxy and 7-oxo metabolites of dehydroepiandrosterone: a role for 11beta-hydroxysteroid dehydrogenasesArch Biochem Biophys.(2003 Apr 15)
- ^Muller C, Cluzeaud F, Pinon GM, Rafestin-Oblin ME, Morfin RDehydroepiandrosterone and its 7-hydroxylated metabolites do not interfere with the transactivation and cellular trafficking of the glucocorticoid receptorJ Steroid Biochem Mol Biol.(2004 Dec)
- ^Mo Q, Lu SF, Simon NGDehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activityJ Steroid Biochem Mol Biol.(2006 Apr)
- ^Miller KK, Al-Rayyan N, Ivanova MM, Mattingly KA, Ripp SL, Klinge CM, Prough RADHEA metabolites activate estrogen receptors alpha and betaSteroids.(2013 Jan)
- ^Granata OM, Cocciadifero L, Campisi I, Miceli V, Montalto G, Polito LM, Agostara B, Carruba GAndrogen metabolism and biotransformation in nontumoral and malignant human liver tissues and cellsJ Steroid Biochem Mol Biol.(2009 Feb)
- ^Hu Y, Ghosh S, Amleh A, Yue W, Lu Y, Katz A, Li RModulation of aromatase expression by BRCA1: a possible link to tissue-specific tumor suppressionOncogene.(2005 Dec 15)
- ^Hammond GL, Wu TS, Simard MEvolving utility of sex hormone-binding globulin measurements in clinical medicineCurr Opin Endocrinol Diabetes Obes.(2012 Jun)