The role of 5-α-reductase inhibition in supressing progression of male androgenetic alopecia − a postulate for further studies on possible application of saw palmetto extracts

• Authors: Marcin Piwecki , Aleksandra Urban , Jolanta Pełszyńska

Title variants

PL

Rola inhibicji 5-α-reduktazy w zatrzymaniu postępu łysienia androgenowego u mężczyzn – postulat na rzecz badań nad zastosowaniem ekstraktów z palmy sabałowej

• Languages of publication: EN PL

Abstracts

EN

The study presents the mechanism of male androgenetic alopecia (MAGA), with a focus on the role of the enzyme 5-α-reductase, which is responsible for converting testosterone, the primary male hormone, into its active form, dihydrotestosterone (DHT). The consequences of the DHT stimulation of androgen receptors (ARs) located in the X chromosome of dermal papilla cells (DPCs) are described. This leads to androgen-induced gene transcription, disrupted hair follicle nourishment, and most importantly, an accelerated transition from the anagen to the catagen phase. The study also discusses how this enzyme can be targeted by molecules acting as inhibitors. Furthermore, the justification for conducting more in-depth studies on the mechanisms of action involving extracts of saw palmetto (Serenoa repens) and their inhibitory effects on 5-α-reductase is presented. The study also advocates the identification and measurement of active substances present in saw palmetto extracts, with two promising phytosterolic compounds, stigmasterol and β-sitosterol, due to their demonstrated inhibitory activity on 5-α-reductase in extracts from other plant species. As part of the proposal to deepen the research, attention is drawn to the need to investigate the impact of saw palmetto extract on the hair growth cycle, hair follicle life cycle, various growth factors and angiogenesis, immune system activity, and oxidative stress. Other areas of observation for the action of saw palmetto extracts could include their use in combination with other plant extracts or therapeutic agents such as platelet-rich plasma or fibrin-rich plasma.

PL

W pracy przedstawiono mechanizm łysienia androgenowego u mężczyzn (male androgenetic alopecia – MAGA) z uwzględnieniem roli enzymu 5-α-reduktazy, która odpowiada za konwersję testosteronu, najważniejszego hormonu męskiego, do jego aktywnej formy – dihydrotestosteronu (DHT). Opisane zostały konsekwencje pobudzenia przez DHT receptorów androgenowych (androgen receptors – ARs), zlokalizowanych w chromosomie X komórek linii brodawkowej (dermal papilla cells – DPCs). Powoduje to transkrypcję genów uruchamianą przez androgeny, zostaje zaburzone odżywianie mieszka włosowego, ale przede wszystkim przyspieszeniu ulega moment zakończenia anagenu i przejścia do fazy katagenu. Przedstawiono również, w jaki sposób enzym ten może być poddawany działaniu molekuł pełniących funkcję jego inhibitorów. Ponadto zaprezentowano uzasadnienie dla prowadzenia bardziej dogłębnych badań poświęconych mechanizmom działania, w których ekstrakty palmy sabałowej (Serenoa repens) wywołują efekt inhibicji 5-α-reduktazy. Dodatkowo w pracy został zawarty postulat na rzecz rozpoznawania i pomiaru substancji aktywnych znajdujących się w ekstraktach palmy sabałowej, w tym dwóch najbardziej obiecujących związków fitosterolowych – stigmasterolu i β-sitosterolu – ze względu na udowodnioną już aktywność inhibitorową w stosunku do 5-α-reduktazy w ekstraktach z surowców pochodzących z innych gatunków roślin. W ramach postulatu na rzecz pogłębienia badań zwrócono uwagę na konieczność oceny wpływu stosowania ekstraktów z palmy sabałowej na cykl życia włosów, cykl życia mieszka włosowego, różne czynniki wzrostu i angiogenezę, a także aktywność układu immunologicznego czy stres oksydacyjny. Inne obszary obserwacji działania ekstraktów z palmy sabałowej mogłyby obejmować ich zastosowanie w terapiach w połączeniu z innymi ekstraktami roślinnymi lub środkami terapii, np. z osoczem bogatopłytkowym czy osoczem bogatym w fibrynę.

Keywords

EN

5-α-reductase; 5-α-reduktaza; androgenetic alopecia; dihydrotestosteron; dihydrotestosterone; hair follicle; inhibitors; inhibitory; mieszek włosowy; palma sabałowa; saw palmetto; steroids; sterole; sterols; sterydy; łysienie androgenowe

Discipline

• MEDICINE: MEDICINE

• Publisher: Śląski Uniwersytet Medyczny w Katowicach
• Journal: Annales Academiae Medicae Silesiensis
• Year: 2023
• Issue: 77
• Pages: 190-196

Contributors

author

Marcin Piwecki

• Perfect Hair Clinic, Katowice, Poland

author

Aleksandra Urban

• Perfect Hair Clinic, Katowice, Poland

author

Jolanta Pełszyńska

• Perfect Hair Clinic, Katowice, Poland

References

• 1. Kwon Y. Use of saw palmetto (Serenoa repens) extract for benign prostatic hyperplasia. Food Sci. Biotechnol. 2019; 28(6): 1599−1606, doi: 10.1007/s10068-019-00605-9.
• 2. Nickel J.C., Chughtai B., De Nunzio C., Brahmbhatt J., Shore N., Te A.E. et al. Rethinking the role of saw palmetto extract for men with lower urinary tract symptoms in North America. Uro 2022; 2(3): 137–150, doi: 10.3390/uro2030017.
• 3. Preston M.A., Wilson K.M., Markt S.C., Ge R., Morash C., Stampfer M.J. et al. 5α-Reductase inhibitors and risk of high-grade or lethal prostate cancer. JAMA Intern. Med. 2014; 174(8): 1301–1307, doi: 10.1001/jamainternmed.2014.1600.
• 4. Koltai T., Reshkin S.J., Baltazar F., Fliegel L. Prostate cancer metabo-lism: From biochemistry to therapeutics. Elsevier, Academic Press. London 2021.
• 5. Evron E., Juhasz M., Babadjouni A., Mesinkovska N.A. Natural hair supplement: Friend or foe? Saw palmetto, a systematic review in alopecia. Skin Appendage Disord. 2020; 6(6): 329−337, doi: 10.1159/000509905.
• 6. He F., Shen M., Zhao Z., Liu Y., Zhang S., Tang Y. et al. Epidemiology and disease burden of androgenetic alopecia in college freshmen in China: A population-based study. PLoS One 2022; 17(2): e0263912, doi: 10.1371/journal.pone.0263912.
• 7. Salman K.E., Altunay I.K., Kucukunal N.A., Cerman A.A. Frequency, severity and related factors of androgenetic alopecia in dermatology outpatient clinic: hospital-based cross-sectional study in Turkey. An. Bras. Dermatol. 2017; 92(1): 35−40, doi: 10.1590/abd1806-4841.20175241.
• 8. Jakubiec M. Androgenetic alopecia in males – characteristics and overview of therapies available in cosmetology and aesthetic medicine clinics. Aesth. Cosmetol. Med. 2022; 11(6): 209−215, doi: 10.52336/acm.2022.030.
• 9. Ho C.H., Sood T., Zito P.M. Androgenetic alopecia. StatPearls, 2021 [online] https://www.ncbi.nlm.nih.gov/books/NBK430924/ [accessed on 10 February 2023].
• 10. Tyszkiewicz M., Pożarowska K., Rosińska A., Orczykowski M. Pharmacotherapy of androgenetic alopecia – a literature review. J. Educ. Health Sport 2022; 12(12): 152−157, doi: 10.12775/JEHS.2022.12.12.024.
• 11. Fu D., Huang J., Li K., Chen Y., He Y., Sun Y. et al. Dihydrotestosterone-induced hair regrowth inhibition by activating androgen receptor in C57BL6 mice simulates androgenetic alopecia. Biomed. Pharmacother. 2021; 137: 111247, doi: 10.1016/j.biopha.2021.111247.
• 12. Carmina E., Azziz R., Bergfeld W., Escobar-Morreale H.F., Futterweit W., Huddleston H. et al. Female pattern hair loss and androgen excess: A report from the Multidisciplinary Androgen Excess and PCOS Committee. J. Clin. Endocrinol. Metab. 2019; 104(7): 2875−2891, doi: 10.1210/jc.2018-02548.
• 13. Fabbrocini G., Cantelli M., Masarà A., Annunziata M.C., Marasca C., Cacciapuoti S. Female pattern hair loss: A clinical, pathophysiologic, and therapeutic review. Int. J. Womens Dermatol. 2018; 4(4): 203−211, doi: 10.1016/j.ijwd.2018.05.001.
• 14. Urysiak-Czubatka I., Kmieć M.L., Broniarczyk-Dyła G. Assessment of the usefulness of dihydrotestosterone in the diagnostics of patients with androgenetic alopecia. Postepy Dermatol. Alergol. 2014; 31(4): 207−215, doi: 10.5114/pdia.2014.40925.
• 15. Konrakhina I.N., Mareeva A.N., Kalinina P.A., Abuladze M.G. Androgenic hormone profile in patients with androgenetic alopecia. Vestn. Dermatol. Venerol. 2015; 91(6): 30–32, doi: 10.25208/0042-4609-2015-91-6-30-32.
• 16. Pindado-Ortega C., Saceda-Corralo D., Fernández-Nieto D., Jiménez-Cauhé J., Ortega-Quijano D., Moreno-Arrones Ó.M. et al. Prescribing habits for androgenic alopecia among dermatologists in Spain in 2019–2020: A cross--sectional study. Skin Appendage Disord. 2020; 6(5): 283−286, doi: 10.1159/000509063.
• 17. Arct J., Pytkowska K. Kosmetologia włosów. Edra Urban & Partner. Wrocław 2020.
• 18. Ruiz-Tagle S.A., Figueira M.M., Vial V., Espinoza-Benavides L., Miteva M. Micronutrients in hair loss. Our Dermatol. Online 2018; 9(3): 320−328, doi: 10.7241/ourd.20183.25.
• 19. O’Connor K., Goldberg L.J. Nutrition and hair. Clin. Dermatol. 2021; 39(5): 809−818, doi: 10.1016/j.clindermatol.2021.05.008.
• 20. Almohanna H.M., Ahmed A.A., Tsatalis J.P., Tosti A. The role of vitamins and minerals in hair loss: A review. Dermatol. Ther. (Heidelb) 2019; 9(1): 51−70, doi: 10.1007/s13555-018-0278-6.
• 21. Houschyar K.S., Borrelli M.R., Tapking C., Popp D., Puladi B., Ooms M. et al. Molecular mechanisms of hair growth and regeneration: Current understanding and novel paradigms. Dermatology 2020; 236(4): 271−280, doi: 10.1159/000506155.
• 22. Randall V.A. Androgens and human hair growth. Clin. Endocrinol. 1994; 40(4): 439−457, doi: 10.1111/j.1365-2265.1994.tb02483.x.
• 23. Grymowicz M., Rudnicka E., Podfigurna A., Napierała P., Smolarczyk R., Smolarczyk K. et al. Hormonal effects on hair follicles. Int. J. Mol. Sci. 2020; 21(15): 5342, doi: 10.3390/ijms21155342.
• 24. Marchetti P.M., Barth J.H. Clinical biochemistry of dihydrotestosterone. Ann. Clin. Biochem. 2013; 50(Pt 2): 95−107, doi: 10.1258/acb.2012.012159.
• 25. Batista R.L., Mendonca B.B. The molecular basis of 5α-reductase type 2 deficiency. Sex. Dev. 2022; 16(2–3): 171−183, doi: 10.1159/000525119.
• 26. Lee H.G., Kim C.J. Classic and backdoor pathways of androgen biosynthesis in human sexual development. Ann. Pediatr. Endocrinol. Metab. 2022; 27(2): 83−89, doi: 10.6065/apem.2244124.062.
• 27. Fukami M., Homma K., Hasegawa T., Ogata T. Backdoor pathway for dihydrotestosterone biosynthesis: implications for normal and abnormal human sex development. Dev. Dyn. 2013; 242(4): 320−329, doi: 10.1002/dvdy.23892.
• 28. Ceruti J.M., Leirós G.J., Balañá M.E. Androgens and androgen receptor action in skin and hair follicles. Mol. Cell. Endocrinol. 2018; 465: 122−133, doi: 10.1016/j.mce.2017.09.009.
• 29. Zhou X., Jiao Y., Zhang W., Li W. Androgens/androgen receptor in the management of skin diseases. J. Biosci. Med. 2022; 10(12): 180−200, doi: 10.4236/jbm.2022.1012015.
• 30. Lee P., Zhu C.C., Sadick N.S., Diwan A.H., Zhang P.S., Liu J.S. et al. Expression of androgen receptor coactivator ARA70/ELE1 in androgenic alopecia. J. Cutan. Pathol. 2005; 32(8): 567−571, doi: 10.1111/j.0303-6987.2005.00397.x.
• 31. Zamani P., Mokhtari O., Dehghanian F. Identification of beta-sitosterol and stigmasterol as possible inhibitors of 5 alpha-reductase 1: An in-silico study. Precis. Med. Clin. OMICS 2021; 1(1): e121545, doi: 10.5812/pmco.121545.
• 32. Iannella L., Colamonici C., Curcio D., Botrè F., de la Torre X. 5α-reductase inhibitors: Evaluation of their potential confounding effect on GC-C-IRMS doping analysis. Drug Test. Anal. 2021; 13(11−12): 1852−1861, doi: 10.1002/dta.3134.
• 33. Diviccaro S., Melcangi R.C., Giatti S. Post-finasteride syndrome: An emerging clinical problem. Neurobiol. Stress 2019; 12: 100209, doi: 10.1016/j.ynstr.2019.100209.
• 34. El-Naggar M., El-All A.S.A., El-Naem S.I.A., Abdalla M.M., Rashdan H.R.M. New potent 5α-reductase and aromatase inhibitors derived from 1,2,3-triazole derivative. Molecules 2020; 25(3): 672, doi: 10.3390/molecules25030672.
• 35. Sudeep H.V., Venkatakrishna K., Amrutharaj B., Anitha G.R.J., Shyamprasad K. A phytosterol-enriched saw palmetto supercritical CO2 extract ameliorates testosterone-induced benign prostatic hyperplasia by regulating the inflammatory and apoptotic proteins in a rat model. BMC Complement. Altern. Med. 2019; 19(1): 270, doi: 10.1186/s12906-019-2697-z.
• 36. Nguyen J., Korta D.Z., Mensinkovska N.A. Hair supplements. In: M.I. Miteva [ed]. Alopecia. Elsevier; 2018, pp. 295–304.
• 37. Niederprüm H.J., Schweikert H.U., Zänker K.S. Testosterone 5α-reductase inhibition by free fatty acids from Sabal serrulata fruits. Phytomedicine 1994; 1(2): 127−133, doi: 10.1016/S0944-7113(11)80030-9.
• 38. Wolski J.K. Serenoa repens – is it worth to apply in andrology? [Article in Polish]. Adv. Androl. Online 2016; 3(1): 33−38.
• 39. Nestor M.S., Ablon G., Gade A., Han H., Fischer D.L. Treatment options for androgenetic alopecia: Efficacy, side effects, compliance, financial considerations, and ethics. J. Cosmet. Dermatol. 2021; 20(12): 3759−3781, doi: 10.1111/jocd.14537.

• Document Type: article