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DOI: 10.1055/s-0031-1301280
Aromatase Activity After a Short-course of Letrozole Administration in Adult Men at Sea Level and at High Altitude (with or without Excessive Erythrocytosis)
Publikationsverlauf
received 04. September 2011
accepted 20. Dezember 2011
Publikationsdatum:
24. Januar 2012 (online)
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Abstract
Men living at high altitudes in Peru compared to sea level counterparts have erythrocytosis (hemoglobin 16–21 g/dl) or excessive erythrocytosis (hemoglobin>21 g/dl). High testosterone (T) levels in men at high altitude (HA) were associated with excessive erythrocytosis. High androgen levels could be due to a low aromatase activity or to an elevated rate of conversion from precursors to testosterone. The aim of this study was to evaluate aromatase activity and rate of conversion from precursors to testosterone before and after administration of the aromatase enzyme inhibitor letrozole (5 mg/day) for a 5-day period to men at HA and at sea level (SL). The response to short term aromatase inhibition was assessed in 30 adult men living at sea level, 31 native men at HA with erythrocytosis (Hb 16–21 g/dl), and 35 men at HA with excessive erythrocytosis (Hb>21 g/dl). Serum hormone levels, estradiol/testosterone, testosterone/androstenedione, and testosterone/dehydroepiandrosterone sulfate (DHEAS) ratios were measured. Men with erythrocytosis had lower basal serum T/androstenedione ratios than men with excessive erythrocytosis at HA and men at sea level. Men at HA with excessive erythrocytosis had higher T/DHEAS ratios than men with erythrocytosis and than those at sea level before and after letrozole administration. After letrozole administration, both groups of men at high altitude (with erythrocytosis or with excessive erythrocytosis) showed lower aromatase activities than those at sea level. In conclusion, higher serum testosterone levels in men with excessive erythrocytosis were associated with an increased rate of conversion from DHEAS to testosterone rather than to a lower aromatase activity.
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References
- 1 Gonzales GF, Gasco M, Tapia V, Gonzales-Castañeda C. High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men. Am J Physiol Endocrinol Metab 2009; 296: E1319-E1325
- 2 Hero M, Wickman S, Hanhijärvi R, Simes MA, Dunkel L. Pubertal upregulation of erythropoiesis in boys is determined primarily by androgen. J Pediatrics 2005; 146: 245-252
- 3 Reeves JT, Leon-Velarde F. Chronic mountain sickness: recent studies of the relationship between hemoglobin concentration and oxygen transport. High Alt Med Biol 2004; 5: 147-155
- 4 Rochira V, Zirilli L, Madeo B, Maffei L, Carani C. Testosterone action on erythropoiesis does not require its aromatization to estrogen: Insights from the testosterone and estrogen treatment of two aromatase-deficient men. J Steroid Biochem Mol Biol 2009; 113: 189-194
- 5 Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD. Aromatase cytochrome p450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994; 15: 342-355
- 6 Pepe CM, Saraco NI, Baquedano MS, Guercio G, Vaiani E, Berensztein E, Rivarola MA, Belgorosky A. Exon 5 alternative splicing of the cytochrome P450 aromatase could be a regulatory mechanism for estrogen production in humans. Medicina (B Aires) 2007; 67: 369-373
- 7 Ma CX, Adjei AA, Salavaggione OE, Coronel J, Pelleymounter L, Wang L, Eckloff BW, Schaid D, Wieben ED, Adjei AA, Weinshilboum RM. Human aromatase: Gene resequencing and functional genomics. Cancer Res 2005; 65: 11071-11082
- 8 Naessen T, Sjogren U, Bergquist J, Larsson M, Lind L, Kushnir MM. Endogenous steroids measured by high-specificity liquid chromatography-tandem mass spectrometry and prevalent cardiovascular disease in 70-year-old men and women. J Clin Endocrinol Metab 2010; 95: 1889-1897
- 9 Allvin K, Ankarberg-Lindgren C, Fors H, Dahlgren J. Elevated serum levels of estradiol, dihydrotestosterone, and inhibin B in adult males born small for gestational age. J Clin Endocrinol Metab 2008; 93: 1464-1469
- 10 Andersson S, Moghrabi N. Physiology and molecular genetics of 17 beta-hydroxysteroid dehydrogenases. Steroids 1997; 62: 143-147
- 11 Mindnich R, Haller F, Halbach F, Moeller G, Hrabé de Angelis M, Adamski J. Androgen metabolism via 17 beta-hydroxysteroid dehydrogenase type 3 in mammalian and non-mammalian vertebrates: comparison of the human and the zebrafish enzyme. J Mo Endocrinol 2005; 35: 305-316
- 12 Lota RK, Olusanjo MS, Dhanani S, Owen CP, Ahmed S. Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of 4-hydroxyphenyl ketones as potent and specific inhibitors of the type 3 of 17beta-hydroxysteroid dehydrogenase (17beta-HSD3). J Steroid Biochem Mol Biol 2008; 111: 128-137
- 13 Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril 2009; 92: 849-852
- 14 Noriega-Portella L, Noriega-Hoces L, Delgado A, Rubio J, Gonzales-Castañeda C, Gonzales GF. Effect of letrozole at 2.5 mg or 5.0 mg/day on ovarian stimulation with gonadotropins in women undergoing intrauterine insemination. Fertil Steril 2008; 90: 1818-1825
- 15 Saylam B, Efesoy O, Cayan S. The effect of aromatase inhibitor letrozole on body mass index, serum hormones, and sperm parameters in infertile men. Fertil Steril 2011; 95: 809-811
- 16 Krone N, Hughes BA, Lavery GG, Stewart PM, Arlt W, Shackleton CH. Gas chromatography/mass spectrometry (GC/MS) remains a pre-eminent discovery tool in clinical steroid investigations even in the era of fast liquid chromatography tandem mass spectrometry (LC/MS/MS). J Steroid Biochem Mol Biol 2010; 121: 496-504
- 17 Gonzales GF, Tapia V, Gasco M, Gonzales-Castañeda C. Serum testosterone levels and score of chronic mountain sickness in Peruvian men natives at 4340 m. Andrologia 2011; 43: 189-195
- 18 Friedrich N, Rosskopf D, Brabant G, Völzke H, Nauck M, Wallaschofski H. Associations of Anthropometric Parameters with Serum TSH, Prolactin, IGF-I, and Testosterone Levels: Results of the Study of Health in Pomerania (SHIP). Exp Clin Endocrinol Diabetes 2010; 118: 266-273
- 19 Gonzales GF, Tapia V, Gasco M, Rubio J, Gonzales-Castañeda C. High serum zinc and serum testosterone levels associated with excessive erythrocytosis in men at high altitudes. Endocrine 2011; 40: 472-480
- 20 Caldwell JD, Jirikowski GF. Sex Hormone Binding Globulin and Aging. Horm Metab Res 2009; 41: 173-182
- 21 Gonzales GF, Góñez C, Villena A. Adrenopause or decline of serum adrenal androgens with age in women living at sea level or at high altitude. J Endocrinol 2002; 173: 95-101
- 22 Snyder CN, Clark RV, Caricofe RB, Bush MA, Roth MY, Page ST, Bremner WJ, Amory JK. Pharmacokinetics of 2 novel formulations of modified-release oral testosterone alone and with finasteride in normal men with experimental hypogonadism. J Androl 2010; 31: 527-535
- 23 Goudriaan AE, Lapauw B, Ruige J, Feyen E, Kaufman JM, Brand M, Vingerhoets G. The influence of high-normal testosterone levels on risk-taking in healthy males in a 1-week letrozole administration study. Psychoneuroendocrinology 2010; 35: 1416-1421
- 24 Rochira V, Zirilli L, Genazzani AD, Balestrieri A, Aranda C, Fabre B, Antunez P, Diazzi C, Carani C, Maffei L. Hypothalamic-pituitary-gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negativa feedback. Eur J Endocrinol 2006; 155: 513-522
- 25 Merlotti D, Gennari L, Stolakis K, Nuti R. Aromatase activity and bone loss in men. J Osteoporosis 2011; 2011: 230671
- 26 Loves S, Ruinemans-Koerts J, de Boer H. Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. Eur J Endocrinol 2008; 158: 741-747
- 27 Vottero A, Rochira V, Capelletti M, Viani I, Zirilli L, Neri TM, Carani C, Bernasconi S, Ghizzoni L. Aromatase is differentially expressed in peripheral blood leukocytes from children, and adult female and male subjects. Eur J Endocrinol 2006; 154: 425-431
- 28 Raven G, de Jong FH, Kaufman JM, de Ronde W. In men, peripheral estradiol levels directly reflect the action of estrogens at the hypothalamo-pituitary level to inhibit gonadotropin secretion. J Clin Endocrinol Metab 2006; 91: 3324-3328
- 29 Scott HM, Mason JI, Sharpe RM. Steroidogenesis in the fetal testis and its susceptibility to disruption by exogenous compounds. Endocr Rev 2009; 30: 883-925
- 30 Ring HZ, Lessov CN, Reed T, Marcus R, Holloway L, Swan GE, Carmelli D. Heritability of plasma sex hormones and hormone binding globulin in adult male twins. J Clin Endocrinol Metab 2005; 90: 3653-3658
- 31 Moore LG, Niermeyer S, Vargas E. Does chronic mountain sickness (CMS) have perinatal origin?. Respir Physiol Neurobiol 2007; 158: 180-189