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Steroid Pathways Spironolactone84, Dexamethasone85, Adrenal Gland (+) 86 84 87 Ketoconazole29, Bile Acid , St

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Steroid Pathways Spironolactone84, Dexamethasone85, Adrenal Gland (+) 86 84 87 Ketoconazole29, Bile Acid , St Primary hormones (in CAPS) are made by organs by taking up cholesterol and converting it locally to, for example, progesterone. Much less is made from circulating DHEAS (Sulfate) precursors like pregnenolone. For example, taking DHEA can create testosterone and estrogen, but far less than is made by the testes or ovaries, respectively. Where is it made? Steroid Pathways Spironolactone84, dexamethasone85, Adrenal gland (+) 86 84 87 Ketoconazole29, bile acid , St. John's Wort , forskolin Find these Hormones on the DUTCH Report 30 spironolactone , Licorice root34, 35, spironolactone37, azole 88 88 89 apigenin, polyphenols31, 32 antifungals38, hyperglycemia27, apegenin31, 38 Low cysteine , inflammation , LPS , www.dutchtest.com (–) ketoconazole88, progestin88, licorice90 (–) (–) 17-hydroxylase 17,20 Lyase 17βHSD Pregnenolone 17-OH-Pregnenolone DHEA Androstenediol Where is it made? 4 Testes in men, from the ovaries (+) Isoflavonoids/phytoestrogens , (+) (–) phthalates, organochlorines, BPA5, (–) and adrenal DHEA in women. Where is it made? 33 5 Hyperglycemia27, PCBs , DHEA ketoconazole , finasteride, dutasteride Ovaries – less from 7 34 28 supplements , obesity 1 2 3βHSD 3βHSD hyperinsulinemia 3βHSD adrenals 3βHSD (+) Fenugreek , high ACTH/hyperadrenalism , Enterolactone, apigenin, genistein, 3 (+) PCOS chrysin and other flavoniods52,white button mushrooms53, grape seed extract, red wine 17-hydroxylase 17,20 Lyase 17βHSD 17-OH-Progesterone 55 56 PROGESTERONE Androstenedione TESTOSTERONE (–) procyanidin dimers , PCOS , antifungal 5β 57 58 59 α medications , metformin glyphosate , Aromatase (CYP19) Aromatase (CYP19) 5β *5 α Etiocholanolone 5β aromatase inhibitors (letrozole, anastrozole) *5 *5 α CYP21 Epi-Testosterone 5α-DHT 46 a- Pregnanediol β- Pregnanediol 5β-Androstanediol Obesity and inflammation , high (+) insulin47, forskolin48, quercetin, 3αHSD 49 EGCG20, PCOS8, curcumin21, genistein (bioflavonoids) , white Where is it More Cortisone: 17βHSD 50 51 7-keto-DHEA19, progesterone19, coffee22, holy peony and licorice root , atrazine , *5α-Reductase/5β-Reductase made? Androsterone 5α-Androstanediol 39 23 24 19, 26 rutin Adrenal gland basil , bitter melon , hyperthyroidism , 5α-Reductase is best known because it makes 19 19 high estrogens , glucocorticoids 39 41 4, 34, 35 4,38 androgens like testosterone more potent. It is CYP11b1 Rutin , alcohol , abdominal Licorice , apigenin , obesity42, bioflavonoids43 pyhtoestrogens4, 43, atrazine45 also responsible for metabolizing progesterone (–) and cortisol. If up-regulated, it may cause high (+) androgen symptoms in men (thinning hair, CORTISOL 11β-HSD Cortisone Estrone (E1) 17βHSD ESTRADIOL (E2) prostate) and women (as in PCOS, thinning hair, (active) (inactive) Where is it made? Ovaries – lesser acne, facial hair growth). 5β-Metabolites are less St. John's Wort74, pesticides75, caffeine62, smoking62, (+) (+) amounts elsewhere androgenic (weaker). CYP-3A4 PAHs74, moderate alcohol consumption68, obesity68 3A4 More Cortisol: Insulin from DHEA/ 5β * α 6, 17 resistance, obesity , 5β Testosterone. CYP-1B1 *5 18 19, 5α-Reductase is increased in particular by: Insulin inflammation , glucocorticoids * (–) Grapefruit60, resveratrol60, rosemary65, wild yam77, 25 (–) 6 7 hypothyroidism , licorice peppermint oil78, azole antifungals79 resistance and obesity , DHEA supplementation , 19 8 root , phthalates, organotins, PCOS alkylphenols19, mother's 19 CYP-1A1 17βHSD diet during pregnancy , 16-OHE 1 Estriol (E3) 5α-Reductase may be decreased by: Saw palmetto progesterone19 9 10 11 and beta-sitosterol , reishi , nettle root , Pygeum Flavonoids73, resveratrol71 africanum12, PUFA and EGCG13 (–) *CYP3A4 Inflammation70, smoking71, PAHs69 Many common medications induce CYP3A4, 5β-Reductase may be affected by some of the (+) including but not limited to, phenobarbitol, above listed things as well (often to a lesser phenytoin, rifampicin, and glucocorticoids. degree). α-THF THF THE COMT Common medications interfere with or 4-OHE1 4-MeOE1 competitively inhibit CYP3A4 including cimetidine, tamoxifen, quinolones, fluoxetine, 5β-Reductase may be increased by: Insulin Cortisol Metabolism/Clearance Cruciferous vegetables60, DIM/IC361, 14 15 etc... resistance, high triglycerides , PCOS Cortisol is metabolized by 5α/5β-reductase (and 3α-HSD) to α/β-THF & THE caffeine62, soy63, fish oil64, rosemary for excretion. This process is particularly increased in obesity, high insulin (+) 65 66, 67 Estradiol80, phthalate esters81, rhodiola rosea, 16 (–) extract , thyroxine flaxseed 5β-Reductase may be decreased by: Licorice and hyperthyroid. It may be slowed in cases of hypothyroidism, anorexia or quercetin, catechin and epicatechin83 poor liver function. (–) 2-OHE1 COMT 2-MeOE1 (+) 67 The information on this chart is for educational purposes only and is not a suggestion for supplementation with any of the listed items. High sugar diet , moderate alcohol SAM-e, magnesium, B6, B12, folate, consumption68, resveratrol and Please see the DUTCH Test Treatment Guide for other factors affecting the production of primary reproductive and adrenal hormones. betaine (cofactors) pterostilbene69 References 23. Jothie Richard, E., et al., Anti-stress Activity of Ocimum sanctum: 48. Watanabe, M. and S. Nakajin, Forskolin up-regulates aromatase 71. Li, M.Y., et al., Estrogen receptor alpha promotes smoking-carcin- Possible Effects on Hypothalamic-Pituitary-Adrenal Axis.Phytother (CYP19) activity and gene transcripts in the human adrenocortical ogen-induced lung carcinogenesis via cytochrome P450 1B1. J Mol 1. Hamden, K., et al., Potential protective effect on key steroidogen sis Res, 2016. 30(5): p. 805-14. carcinoma cell line H295R. J Endocrinol, 2004. 180(1): p. 125-33. Med (Berl), 2015. 93(11): p. 1221-33. and metabolic enzymes and sperm abnormalities by fenugreek ste- 24. Blum, A., et al., Momordica charantia extract, a herbal remedy for 49. Sanderson, J.T., et al., Induction and inhibition of aromatase 72. Jaramillo, I.C., et al., Effects of fuel components and combustion roids in testis and epididymis of surviving diabetic rats. Arch Physiol type 2 diabetes, contains a specific 11β-hydroxysteroid dehydroge- (CYP19) activity by natural and synthetic flavonoid compounds in particle physicochemical properties on toxicological responses of Biochem, 2010. 116(3): p. 146-55. nase type 1 inhibitor. J Steroid Biochem Mol Biol, 2012. 128(1-2): p. H295R human adrenocortical carcinoma cells. Toxicol Sci, 2004. lung cells. J Environ Sci Health A Tox Hazard Subst Environ Eng, 2018. 2. Simonian, M.H., ACTH and thyroid hormone regulation of 3 be- 51-5. 82(1): p. 70-9. 53(4): p. 295-309. ta-hydroxysteroid dehydrogenase activity in human fetal adreno- 25. Hoshiro, M., et al., Comprehensive study of urinary cortisol me- 50. Takeuchi, T., et al., Effect of paeoniflorin, glycyrrhizin and glycyr- 73. Doostdar, H., M.D. Burke, and R.T. Mayer, Bioflavonoids: selective cortical cells. J Steroid Biochem, 1986. 25(6): p. 1001-6. tabolites in hyperthyroid and hypothyroid patients. Clin Endocrinol rhetic acid on ovarian androgen production. Am J Chin Med, 1991. substrates and inhibitors for cytochrome P450 CYP1A and CYP1B1. 3. Kaaijk, E.M., et al., Distribution of steroidogenic enzymes involved (Oxf), 2006. 64(1): p. 37-45. 19(1): p. 73-8. Toxicology, 2000. 144(1-3): p. 31-8. in androgen synthesis in polycystic ovaries: an immunohistochemi- 26. Taniyama, M., K. Honma, and Y. Ban, Urinary cortisol metabolites in 51. Holloway, A.C., et al., Atrazine-induced changes in aromatase activ- 74. Whitten, D.L., et al., The effect of St John's wort extracts on CYP3A: cal study. Mol Hum Reprod, 2000. 6(5): p. 443-7. the assessment of peripheral thyroid hormone action: application ity in estrogen sensitive target tissues. J Appl Toxicol, 2008. 28(3): p. a systematic review of prospective clinical trials. Br J Clin Pharmacol, 4. Deluca, D., et al., Inhibition of 17beta-hydroxysteroid dehydroge- for diagnosis of resistance to thyroid hormone. Thyroid, 1993. 3(3): 260-70. 2006. 62(5): p. 512-26. nases by phytoestrogens: comparison with other steroid metabo- p. 229-33. 52. Lephart, E.D., Modulation of Aromatase by Phytoestrogens. Enzyme 75. Bradlow, H.L., et al., Effects of pesticides on the ratio of 16 al- lizing enzymes. J Steroid Biochem Mol Biol, 2005. 93(2-5): p. 285-92. 27. Ueshiba, H., et al., Decreased steroidogenic enzyme 17,20-lyase Res, 2015. 2015: p. 594656. pha/2-hydroxyestrone: a biologic marker of breast cancer risk. 5. Zhang, S., et al., Endocrine disruptors of inhibiting testicular and increased 17-hydroxylase activities in type 2 diabetes mellitus. 53. Novaes, M.R., et al., The effects of dietary supplementation with Environ Health Perspect, 1995. 103 Suppl 7: p. 147-50. 3β-hydroxysteroid dehydrogenase. Chem Biol Interact, 2019. 303: Eur J Endocrinol, 2002. 146(3): p. 375-80. Agaricales mushrooms and other medicinal fungi on breast cancer: 76. 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