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. 1997 Aug 15;100(4):808–813. doi: 10.1172/JCI119595

Contribution of androgens to the gender difference in leptin production in obese children and adolescents.

M Wabitsch 1, W F Blum 1, R Muche 1, M Braun 1, F Hube 1, W Rascher 1, E Heinze 1, W Teller 1, H Hauner 1
PMCID: PMC508252  PMID: 9259579

Abstract

Recent studies demonstrated significantly higher serum leptin concentrations in females as compared with males, even after correction for differences in body fat mass. The aim of our study was to measure serum leptin concentrations in a large group of obese children and adolescents to determine the possible role of sex steroid hormones on both leptin serum concentrations and production in human adipocytes. Obese girls were found to have significantly higher leptin concentrations than boys at the same degree of adiposity (25.2+/-14.1 vs. 17.2+/-12.6 ng/ml, P < 0.001). In a multiple regression analysis with age and body mass index (percent body fat) as fixed variables, it turned out that testosterone had a potent negative effect on serum leptin in boys, but not in girls. In vitro experiments using newly developed human adipocytes in primary culture showed that both testosterone and its biologically active metabolite dihydrotestosterone are able to reduce leptin secretion into the culture medium by up to 62%. Using a semiquantitative reverse transcriptase-PCR method, testosterone was found to suppress leptin mRNA to a similar extent. These results suggest that, apart from differences in body fat mass, the higher androgen concentrations in obese boys are responsible for the lower leptin serum concentrations compared with obese girls.

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Selected References

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  1. Bhasin S., Storer T. W., Berman N., Callegari C., Clevenger B., Phillips J., Bunnell T. J., Tricker R., Shirazi A., Casaburi R. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996 Jul 4;335(1):1–7. doi: 10.1056/NEJM199607043350101. [DOI] [PubMed] [Google Scholar]
  2. CLARK L. C., Jr, GARN S. M. Relationship between ketosteroid excretion and basal oxygen consumption in children. J Appl Physiol. 1954 Mar;6(9):546–550. doi: 10.1152/jappl.1954.6.9.546. [DOI] [PubMed] [Google Scholar]
  3. Campfield L. A., Smith F. J., Guisez Y., Devos R., Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995 Jul 28;269(5223):546–549. doi: 10.1126/science.7624778. [DOI] [PubMed] [Google Scholar]
  4. Caprio S., Tamborlane W. V., Silver D., Robinson C., Leibel R., McCarthy S., Grozman A., Belous A., Maggs D., Sherwin R. S. Hyperleptinemia: an early sign of juvenile obesity. Relations to body fat depots and insulin concentrations. Am J Physiol. 1996 Sep;271(3 Pt 1):E626–E630. doi: 10.1152/ajpendo.1996.271.3.E626. [DOI] [PubMed] [Google Scholar]
  5. Caro J. F., Sinha M. K., Kolaczynski J. W., Zhang P. L., Considine R. V. Leptin: the tale of an obesity gene. Diabetes. 1996 Nov;45(11):1455–1462. doi: 10.2337/diab.45.11.1455. [DOI] [PubMed] [Google Scholar]
  6. Considine R. V., Considine E. L., Williams C. J., Nyce M. R., Magosin S. A., Bauer T. L., Rosato E. L., Colberg J., Caro J. F. Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest. 1995 Jun;95(6):2986–2988. doi: 10.1172/JCI118007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Considine R. V., Sinha M. K., Heiman M. L., Kriauciunas A., Stephens T. W., Nyce M. R., Ohannesian J. P., Marco C. C., McKee L. J., Bauer T. L. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996 Feb 1;334(5):292–295. doi: 10.1056/NEJM199602013340503. [DOI] [PubMed] [Google Scholar]
  8. Halaas J. L., Gajiwala K. S., Maffei M., Cohen S. L., Chait B. T., Rabinowitz D., Lallone R. L., Burley S. K., Friedman J. M. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995 Jul 28;269(5223):543–546. doi: 10.1126/science.7624777. [DOI] [PubMed] [Google Scholar]
  9. Hamilton B. S., Paglia D., Kwan A. Y., Deitel M. Increased obese mRNA expression in omental fat cells from massively obese humans. Nat Med. 1995 Sep;1(9):953–956. doi: 10.1038/nm0995-953. [DOI] [PubMed] [Google Scholar]
  10. Hassink S. G., Sheslow D. V., de Lancey E., Opentanova I., Considine R. V., Caro J. F. Serum leptin in children with obesity: relationship to gender and development. Pediatrics. 1996 Aug;98(2 Pt 1):201–203. [PubMed] [Google Scholar]
  11. Hauner H., Entenmann G., Wabitsch M., Gaillard D., Ailhaud G., Negrel R., Pfeiffer E. F. Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest. 1989 Nov;84(5):1663–1670. doi: 10.1172/JCI114345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Havel P. J., Kasim-Karakas S., Dubuc G. R., Mueller W., Phinney S. D. Gender differences in plasma leptin concentrations. Nat Med. 1996 Sep;2(9):949–950. doi: 10.1038/nm0996-949b. [DOI] [PubMed] [Google Scholar]
  13. Hube F., Lietz U., Igel M., Jensen P. B., Tornqvist H., Joost H. G., Hauner H. Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans. Horm Metab Res. 1996 Dec;28(12):690–693. doi: 10.1055/s-2007-979879. [DOI] [PubMed] [Google Scholar]
  14. Kadonaga J. T., Carner K. R., Masiarz F. R., Tjian R. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell. 1987 Dec 24;51(6):1079–1090. doi: 10.1016/0092-8674(87)90594-0. [DOI] [PubMed] [Google Scholar]
  15. Lönnqvist F., Arner P., Nordfors L., Schalling M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med. 1995 Sep;1(9):950–953. doi: 10.1038/nm0995-950. [DOI] [PubMed] [Google Scholar]
  16. Maffei M., Halaas J., Ravussin E., Pratley R. E., Lee G. H., Zhang Y., Fei H., Kim S., Lallone R., Ranganathan S. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995 Nov;1(11):1155–1161. doi: 10.1038/nm1195-1155. [DOI] [PubMed] [Google Scholar]
  17. Marshall W. A., Tanner J. M. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969 Jun;44(235):291–303. doi: 10.1136/adc.44.235.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marshall W. A., Tanner J. M. Variations in the pattern of pubertal changes in boys. Arch Dis Child. 1970 Feb;45(239):13–23. doi: 10.1136/adc.45.239.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mooradian A. D., Morley J. E., Korenman S. G. Biological actions of androgens. Endocr Rev. 1987 Feb;8(1):1–28. doi: 10.1210/edrv-8-1-1. [DOI] [PubMed] [Google Scholar]
  20. Ostlund R. E., Jr, Yang J. W., Klein S., Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab. 1996 Nov;81(11):3909–3913. doi: 10.1210/jcem.81.11.8923837. [DOI] [PubMed] [Google Scholar]
  21. Pelleymounter M. A., Cullen M. J., Baker M. B., Hecht R., Winters D., Boone T., Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995 Jul 28;269(5223):540–543. doi: 10.1126/science.7624776. [DOI] [PubMed] [Google Scholar]
  22. Ravussin E., Lillioja S., Anderson T. E., Christin L., Bogardus C. Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber. J Clin Invest. 1986 Dec;78(6):1568–1578. doi: 10.1172/JCI112749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rentsch J., Chiesi M. Regulation of ob gene mRNA levels in cultured adipocytes. FEBS Lett. 1996 Jan 22;379(1):55–59. doi: 10.1016/0014-5793(95)01485-3. [DOI] [PubMed] [Google Scholar]
  24. Rico H., Revilla M., Villa L. F., Hernández E. R., Alvarez de Buergo M., Villa M. Body composition in children and Tanner's stages: a study with dual-energy x-ray absorptiometry. Metabolism. 1993 Aug;42(8):967–970. doi: 10.1016/0026-0495(93)90008-c. [DOI] [PubMed] [Google Scholar]
  25. Rosenbaum M., Nicolson M., Hirsch J., Heymsfield S. B., Gallagher D., Chu F., Leibel R. L. Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab. 1996 Sep;81(9):3424–3427. doi: 10.1210/jcem.81.9.8784109. [DOI] [PubMed] [Google Scholar]
  26. Segal K. R., Landt M., Klein S. Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes. 1996 Jul;45(7):988–991. doi: 10.2337/diab.45.7.988. [DOI] [PubMed] [Google Scholar]
  27. Wabitsch M., Braun U., Heinze E., Muche R., Mayer H., Teller W., Fusch C. Body composition in 5-18-y-old obese children and adolescents before and after weight reduction as assessed by deuterium dilution and bioelectrical impedance analysis. Am J Clin Nutr. 1996 Jul;64(1):1–6. doi: 10.1093/ajcn/64.1.1. [DOI] [PubMed] [Google Scholar]
  28. Wabitsch M., Jensen P. B., Blum W. F., Christoffersen C. T., Englaro P., Heinze E., Rascher W., Teller W., Tornqvist H., Hauner H. Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes. 1996 Oct;45(10):1435–1438. doi: 10.2337/diab.45.10.1435. [DOI] [PubMed] [Google Scholar]
  29. Xu X., De Pergola G., Björntorp P. The effects of androgens on the regulation of lipolysis in adipose precursor cells. Endocrinology. 1990 Feb;126(2):1229–1234. doi: 10.1210/endo-126-2-1229. [DOI] [PubMed] [Google Scholar]
  30. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedman J. M. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994 Dec 1;372(6505):425–432. doi: 10.1038/372425a0. [DOI] [PubMed] [Google Scholar]

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