Effects of androgen and progestin on the proliferation and differentiation of osteoblasts

  • Authors:
    • Xinchen Wu
    • Mengqi Zhang
  • View Affiliations

  • Published online on: September 19, 2018     https://doi.org/10.3892/etm.2018.6772
  • Pages: 4722-4728
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Osteoporosis is liable to affect patients with gonadal hormone deficiency, and a supplement of androgens may be used to increase bone density of patients with osteoporosis. Since the androgens currently used may cause severe side effects, it is useful to investigate the effect of other androgens and progestin on bone improvement. The aim of the current study was to investigate the effects of pregnenolone (Preg), androstenedione (AD), etiocholanolone (Etio), androsterone (An), nandrolone (NA) and testosterone (T) on the proliferation and differentiation of osteoblasts for potential clinical applications. Human osteoblasts were cultured and treated with androgens and progestin, including Preg, AD, Etio, An, NA, and T, at concentrations of 0, 10‑10, 10‑8, 10‑6 and 10‑5 mol/l. The levels of cell proliferation, alkaline phosphatase (ALP) activity and osteocalcin content were measured and assessed. Preg, AD, Etio, An, and T at concentrations of 10‑10 and/or 10‑8 mol/l significantly improved osteoblast proliferation. NA at concentrations of 10‑10, 10‑8, 10‑6 and 10‑5 mol/l also significantly improved osteoblast proliferation. Preg, AD, Etio, An, NA, and T significantly increased ALP activity and osteocalcin content. The present study demonstrated, for the first time, that Preg, AD, Etio, An, and NA could improve the proliferation and differentiation of osteoblasts in vitro.

References

1 

Ellis SL, Grassinger J, Jones A, Borg J, Camenisch T, Haylock D, Bertoncello I and Nilsson SK: The relationship between bone, hemopoietic stem cells, and vasculature. Blood. 118:1516–1524. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Felix R, Elford PR, Stoercklé C, Cecchini M, Wetterwald A, Trechsel U, Fleisch H and Stadler BM: Production of hemopoietic growth factors by bone tissue and bone cells in culture. J Bone Miner Res. 3:27–36. 1988. View Article : Google Scholar : PubMed/NCBI

3 

Guntur AR and Rosen CJ: Bone as an endocrine organ. Endocr Pract. 18:758–762. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Cianferotti L and Brandi ML: Muscle-bone interactions: Basic and clinical aspects. Endocrine. 45:165–177. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Rendina E, Hembree KD, Davis MR, Marlow D, Clarke SL, Halloran BP, Lucas EA and Smith BJ: Dried plum's unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model. PLoS One. 8:e605692013. View Article : Google Scholar : PubMed/NCBI

6 

Faienza MF, Ventura A, Marzano F and Cavallo L: Postmenopausal osteoporosis: The role of immune system cells. Clin Dev Immunol. 2013:5759362013. View Article : Google Scholar : PubMed/NCBI

7 

Armas LA and Recker RR: Pathophysiology of osteoporosis: New mechanistic insights. Endocrinol Metab Clin North Am. 41:475–486. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Rachner TD, Khosla S and Hofbauer LC: Osteoporosis: Now and the future. Lancet. 377:1276–1287. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Charles JF and Aliprantis AO: Osteoclasts: More than ‘bone eaters’. Trends Mol Med. 20:449–459. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Clarke BL and Khosla S: Androgens and bone. Steroids. 74:296–305. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Gallagher JC and Tella SH: Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol. 142:155–170. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Jackson RD and Mysiw WJ: Insights into the epidemiology of postmenopausal osteoporosis: The women's health initiative. Semin Reprod Med. 32:454–462. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Bowring CE and Francis RM: National Osteoporosis Society's position statement on hormone replacement therapy in the prevention and treatment of osteoporosis. Menopause Int. 17:63–65. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Tirabassi G, Biagioli A and Balercia G: Bone benefits of testosterone replacement therapy in male hypogonadism. Panminerva Med. 56:151–163. 2014.PubMed/NCBI

15 

Cartwright B, Robinson J, Seed PT, Fogelman I and Rymer J: Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: A randomized controlled trial of the effects on bone mineral density. J Clin Endocrinol Metab. 101:3497–3505. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Jo DG, Lee HS, Joo YM and Seo JT: Effect of testosterone replacement therapy on bone mineral density in patients with Klinefelter syndrome. Yonsei Med J. 54:1331–1335. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Kasperk CH, Wergedal JE, Farley JR, Linkhart TA, Turner RT and Baylink DJ: Androgens directly stimulate proliferation of bone cells in vitro. Endocrinology. 124:1576–1578. 1989. View Article : Google Scholar : PubMed/NCBI

18 

Drake MT and Khosla S: Male osteoporosis. Endocrinol Metab Clin North Am. 41:629–641. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Swartz CM and Young MA: Male hypogonadism and bone fracture. N Engl J Med. 318:9961988. View Article : Google Scholar : PubMed/NCBI

20 

Nieminen MS, Rämö MP, Viitasalo M, Heikkilä P, Karjalainen J, Mäntysaari M and Heikkilä J: Serious cardiovascular side effects of large doses of anabolic steroids in weight lifters. Eur Heart J. 17:1576–1583. 1996. View Article : Google Scholar : PubMed/NCBI

21 

Lamb DR: Anabolic steroids in athletics: How well do they work and how dangerous are they? Am J Sports Med. 12:31–38. 1984. View Article : Google Scholar : PubMed/NCBI

22 

Bassil N, Alkaade S and Morley JE: The benefits and risks of testosterone replacement therapy: A review. Ther Clin Risk Manag. 5:427–448. 2009.PubMed/NCBI

23 

Frick KM, Kim J, Tuscher JJ and Fortress AM: Sex steroid hormones matter for learning and memory: Estrogenic regulation of hippocampal function in male and female rodents. Learn Mem. 22:472–493. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Devlin TM: Textbook of biochemistry: With clinical correlations. 7th. Hoboken; New Jersey: 2010

25 

Kaminski RM, Marini H, Kim WJ and Rogawski MA: Anticonvulsant activity of androsterone and etiocholanolone. Epilepsia. 46:819–827. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Motofei IG: A dual physiological character for cerebral mechanisms of sexuality and cognition: Common somatic peripheral afferents. BJU Int. 108:1634–1639. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Gruyter WD: Concise encyclopedia biology. Berlin: 1996

28 

Marques DRC, Marques D, Ibanez JF, Freitas IB, Hespanha AC, Monteiro JF, Eggert M and Becker A: Effects of nandrolone decanoate on time to consolidation of bone defects resulting from osteotomy for tibial tuberosity advancement. Vet Comp Orthop Traumatol. 30:351–356. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Nawata H, Tanaka S, Tanaka S, Takayanagi R, Sakai Y, Yanase T, Ikuyama S and Haji M: Aromatase in bone cell: Association with osteoporosis in postmenopausal women. J Steroid Biochem Mol Biol. 53:165–174. 1995. View Article : Google Scholar : PubMed/NCBI

30 

da Costa KJ, Passos JJ, Gomes AD, Sinisterra RD, Lanza CR and Cortés ME: Effect of testosterone incorporation on cell proliferation and differentiation for polymer-bioceramic composites. J Mater Sci Mater Med. 23:2751–2759. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Zoch ML, Clemens TL and Riddle RC: New insights into the biology of osteocalcin. Bone. 82:42–49. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Tuck SP and Francis RM: Testosterone, bone and osteoporosis. Front Horm Res. 37:123–132. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Weinstein RS, Jilka RL, Parfitt AM and Manolagas SC: The effects of androgen deficiency on murine bone remodeling and bone mineral density are mediated via cells of the osteoblastic lineage. Endocrinology. 138:4013–4021. 1997. View Article : Google Scholar : PubMed/NCBI

34 

Diamond TH, Higano CS, Smith MR, Guise TA and Singer FR: Osteoporosis in men with prostate carcinoma receiving androgen-deprivation therapy: Recommendations for diagnosis and therapies. Cancer. 100:892–899. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Daniell HW, Dunn SR, Ferguson DW, Lomas G, Niazi Z and Stratte PT: Progressive osteoporosis during androgen deprivation therapy for prostate cancer. J Urol. 163:181–186. 2000. View Article : Google Scholar : PubMed/NCBI

36 

Sessa G and Weissmann G: Differential effecs of etiocholanolone on phospholipid/cholesterol structures containing either testosterone or estradiol. Biochim Biophys Acta. 150:173–180. 1968. View Article : Google Scholar : PubMed/NCBI

37 

Novak FJ and Lambert JG: Pregnenolone, testosterone, and estradiol in the migratory locust Locustamigratoria; a gas chromatographical-mass spectrometrical study. Gen Comp Endocrinol. 76:73–82. 1989. View Article : Google Scholar : PubMed/NCBI

38 

Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N and Ratnam K: Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem J. 351:67–77. 2000. View Article : Google Scholar : PubMed/NCBI

39 

Kamrath C, Hochberg Z, Hartmann MF, Remer T and Wudy SA: Increased activation of the alternative ‘backdoor’ pathway in patients with 21-hydroxylase deficiency: Evidence from urinary steroid hormone analysis. J Clin Endocrinol Metab. 97:E367–E375. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Tsitsimpikou C, Vasilaki F, Tsarouhas K, Fragkiadaki P, Tzardi M, Goutzourelas N, Nepka C, Kalogeraki A, Heretis I, Epitropaki Z, et al: Nephrotoxicity in rabbits after long-term nandrolone decanoate administration. Toxicol Lett. 259:21–27. 2016. View Article : Google Scholar : PubMed/NCBI

41 

Belardin LB, Simão VA, Leite GA, Chuffa LG and Camargo IC: Dose-dependent effects and reversibility of the injuries caused by nandrolone decanoate in uterine tissue and fertility of rats. Birth Defects Res B Dev Reprod Toxicol. 101:168–177. 2014. View Article : Google Scholar : PubMed/NCBI

42 

The biological properties of etiocholanolone, . Combined clinical staff conference at the National Institutes of Health. Ann Intern Med. 67:1268–1295. 1967. View Article : Google Scholar : PubMed/NCBI

43 

Kaminski RM, Marini H, Kim WJ and Rogawski MA: Anticonvulsant activity of androsterone and etiocholanolone. Epilepsia. 46:819–827. 2005. View Article : Google Scholar : PubMed/NCBI

44 

Roux BM, Akar B, Zhou W, Stojkova K, Barrera B, Brankov JG and Brey EM: Preformed vascular networks survive and enhance vascularization in critical sized cranial defectsTissue Eng Part A. 2018, View Article : Google Scholar : (Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

45 

Pirraco RP, Iwata T, Yoshida T, Marques AP, Yamato M, Reis RL and Okano T: Endothelial cells enhance the in vivo bone-forming ability of osteogenic cell sheets. Lab Invest. 94:663–673. 2014. View Article : Google Scholar : PubMed/NCBI

46 

Cai J, Hong Y, Weng C, Tan C, Imperato-McGinley J and Zhu YS: Androgen stimulates endothelial cell proliferation via an androgen receptor/VEGF/cyclin A-mediated mechanism. Am J Physiol Heart Circ Physiol. 300:H1210–H1221. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

December 2018
Volume 16 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wu, X., & Wu, X. (2018). Effects of androgen and progestin on the proliferation and differentiation of osteoblasts. Experimental and Therapeutic Medicine, 16, 4722-4728. https://doi.org/10.3892/etm.2018.6772
MLA
Wu, X., Zhang, M."Effects of androgen and progestin on the proliferation and differentiation of osteoblasts". Experimental and Therapeutic Medicine 16.6 (2018): 4722-4728.
Chicago
Wu, X., Zhang, M."Effects of androgen and progestin on the proliferation and differentiation of osteoblasts". Experimental and Therapeutic Medicine 16, no. 6 (2018): 4722-4728. https://doi.org/10.3892/etm.2018.6772