Abstract
OBJECTIVE: To investigate the associations between sex hormones and leptin. In addition, to investigate the direct effect of sex hormones by incubations of human subcutaneous adipose tissue explants, in vitro.
DESIGN: Cross-sectional study and an experimental in vitro study.
SUBJECTS: 36 women (age, 23–65 y; body mass index, BMI, 19–65 kg/m2) participated in the cross-sectional study. Subcutaneous abdominal biopsies were taken from nine women (age, 28–46 y; BMI, 25.5–36.0 kg/m2) for the in vitro study.
MEASUREMENTS: Fat distribution parameters (by dual-energy X-ray absorptiometry and anthropometry), sex hormones, leptin and insulin.
RESULTS: Leptin correlated significantly with most estimates of adipose tissue mass (r=0.5–0.9, P<0.05). However, when the study group was divided in three equal groups (non-obese, obese, and very-obese) it revealed that the correlation predominantly was found in non-obese. In simple correlation analysis leptin was significantly associated with estimates of adipose tissue, insulin and several sex hormones. However, in multiple regression analysis only insulin (partial correlation coefficient=0.55, P<0.004) and percentage fat mass (partial correlation coefficient=0.72, P<0.001) were significantly and independently correlated with leptin without any independent effect of sex hormones. These findings were in agreement with the in vitro studies where neither estrogen nor androgens (testosterone or DHT) affected subcutaneous adipose tissue leptin production. Dexamethasone (10 nM) stimulated adipose tissue leptin production 3-fold (P<0.001).
CONCLUSION: In regression analysis, where both insulin and measurements of fat mass were taken into account, androgens or estrogens did not independently contribute to the variation in leptin levels. Estrogens and androgens had no direct effects on adipose tissue leptin production in vitro. Thus, the sexual dimorphism evident in serum leptin is not likely to be due to a direct influence of sex hormones on leptin production in females.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, 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 Nature Med 1995 1: 1155–1161.
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF . Serum immunoreactive-leptin concentrations in normal-weight and obese humans New Engl J Med 1996 334: 292–295.
Andersen PH, Kristensen K, Pedersen SB, Hjollund E, Schmitz O, Richelsen B . Effects of long-term total fasting and insulin on ob gene expression in obese patients Eur J Endocrinol 1997 137: 229–233.
Kolaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro JF . Response of leptin to short-term and prolonged overfeeding in humans J Clin Endocrinol Metab 1996 81: 4162–4165.
Wabitsch M, Jensen PB, Blum WF, Christoffersen CT, 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 45: 1435–1438.
Miell JP, Englaro P, Blum WF . Dexamethasone induces an acute and sustained rise in circulating leptin levels in normal human subjects Horm Metab Res 1996 28: 704–707.
Vidal H, Auboeuf D, De Vos P, Staels B, Riou JP, Auwerx J, Laville M . The expression of ob gene is not acutely regulated by insulin and fasting in human abdominal subcutaneous adipose tissue J Clin Invest 1996 98: 251–255.
Dagogo-Jack S, Fanelli C, Paramore D, Brothers J, Landt M . Plasma leptin and insulin relationships in obese and nonobese humans Diabetes 1996 45: 695–698.
Kosaki A, Yamada K, Kuzuya H . Reduced expression of the leptin gene (ob) by catecholamine through a G(S) protein-coupled pathway in 3T3-L1 adipocytes Diabetes 1996 45: 1744–1749.
Schrauwen P, van Marken Lichtenbelt WD, Westerterp KR, Saris WH . Effect of diet composition on leptin concentration in lean subjects Metabolism 1997 46: 420–424.
Hickey MS, Houmard JA, Considine RV, Tyndall GL, Midgette JB, Gavigan KE, Weidner ML, McCammon MR, Israel RG, Caro JF . Gender-dependent effects of exercise training on serum leptin levels in humans Am J Physiol 1997 272: E562–E566.
Saad MF, Damani S, Gingerich RL, Riad-Gabriel MG, Khan A, Boyadjian R, Jinagouda SD, el-Tawil K, Rude RK, Kamdar V . Sexual dimorphism in plasma leptin concentration J Clin Endocrinol Metab 1997 82: 579–584.
Baumgartner RN, Ross RR, Waters DL, Brooks WM, Morley JE, Montoya GD, Garry PJ . Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes Obes Res 1999 7: 141–149.
Montague CT, Prins JB, Sanders L, Digby JE, O'Rahilly S . Depot-and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution Diabetes 1997 46: 342–347.
Wabitsch M, Blum WF, Muche R, Braun M, Hube F, Rascher W, Heinze E, Teller W, Hauner H . Contribution of androgens to the gender difference in leptin production in obese children and adolescents J Clin Invest 1997 100: 808–813.
Elbers JM, Asscheman H, Seidell JC, Frolich M, Meinders AE, Gooren LJ . Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals J Clin Endocrinol Metab 1997 82: 3267–3270.
Mannucci E, Ognibene A, Becorpi A, Cremasco F, Pellegrini S, Ottanelli S, Rizzello SM, Massi G, Messeri G, Rotella CM . Relationship between leptin and oestrogens in healthy women Eur J Endocrinol 1998 139: 198–201.
Mills PJ, Ziegler MG, Morrison TA . Leptin is related to epinephrine levels but not reproductive hormone levels in cycling African-American and Caucasian women Life Sci 1998 63: 617–623.
Teirmaa T, Luukkaa V, Rouru J, Koulu M, Huupponen R . Correlation between circulating leptin and luteinizing hormone during the menstrual cycle in normal-weight women Eur J Endocrinol 1998 139: 190–194.
Haffner SM, Mykkanen L, Stern MP . Leptin concentrations in women in the San Antonio Heart Study: effect of menopausal status and postmenopausal hormone replacement therapy Am J Epidemiol 1997 146: 581–585.
Kohrt WM, Landt M, Birge SJ Jr . Serum leptin levels are reduced in response to exercise training, but not hormone replacement therapy, in older women J Clin Endocrinol Metab 1996 81: 3980–3985.
Kristensen K, Pedersen SB, Vestergaard P, Mosekilde L, Richelsen B . Hormone replacement therapy affects body composition and leptin differently in obese and non-obese postmenopausal women J Endocrinol 1999 163: 55–62.
Jockenhovel F, Blum WF, Vogel E, Englaro P, Mullerwieland D, Reinwein D, Rascher W, Krone W . Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men J Clin Endocrinol Metab 1997 82: 2510–2513.
Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A . Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism J Clin Endocrinol Metab 1996 81: 4358–4365.
Kristensen K, Pedersen SB, Langdahl BL, Richelsen B . Regulation of leptin by thyroid hormone in humans: studies in vivo and in vitro Metabolism 1999 48: 1603–1607.
Mandrup S, Loftus TM, MacDougald OA, Kuhajda FP, Lane MD . Obese gene expression at in vivo levels by fat pads derived from s.c. implanted 3T3-F442A preadipocytes Proc Natl Acad Sci USA 1997 94: 4300–4305.
Pineiro V, Casabiell X, Peino R, Lage M, Camina JP, Menendez C, Baltar J, Dieguez C, Casanueva F . Dihydrotestosterone, stanozolol, androstenedione and dehydroepiandrosterone sulphate inhibit leptin secretion in female but not in male samples of omental adipose tissue in vitro: lack of effect of testosterone J Endocrinol 1999 160: 425–432.
Dieudonne MN, Pecquery R, Boumediene A, Leneveu MC, Giudicelli Y . Androgen receptors in human preadipocytes and adipocytes: regional specificities and regulation by sex steroids Am J Physiol 1998 274: C1645–C1652.
Weigle DS, Ganter SL, Kuijper JL, Leonetti DL, Boyko EJ, Fujimoto WY . Effect of regional fat distribution and Prader-Willi syndrome on plasma leptin levels J Clin Endocrinol Metab 1997 82: 566–570.
Wupeng S, Rosenbaum M, Nicolson M, Chua SC, Leibel RL . Effects of exogenous gonadal steroids on leptin homeostasis in rats Obes Res 1999 7: 586–592.
Baumgartner RN, Ross RR, Waters DL, Brooks WM, Morley JE, Montoya GD, Garry PJ . Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes Obes Res 1999 7: 141–149.
Carmina E, Ferin M, Gonzalez F, Lobo RA . Evidence that insulin and androgens may participate in the regulation of serum leptin levels in women Fertil Steril 1999 72: 926–931.
Ozata M, Ozisik G, Caglayan S, Yesilova Z, Bingol N, Saglam M, Turan M, Beyhan Z . Effects of gonadotropin and testosterone treatments on plasma leptin levels in male patients with idiopathic hypogonadotropic hypogonadism and Klinefelter's syndrome Horm Metab Res 1998 30: 266–271.
Luukkaa V, Pesonen U, Huhtaniemi I, Lehtonen A, Tilvis R, Tuomilehto T, Koulu M, Huupponen R . Inverse correlation between serum testosterone and leptin in men J Clin Endocrinol Metab 1998 83: 3243–3246.
Plymate SR, Matej LA, Jones RE, Friedl KE . Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin J Clin Endocrinol Metab 1988 67: 460–464.
Strain G, Zumoff B, Rosner W, Pi-Sunyer X . The relationship between serum levels of insulin and sex hormone-binding globulin in men: the effect of weight loss J Clin Endocrinol Metab 1994 79: 1173–1176.
Falkner B, Sherif K, Sumner A, Kushner H . Hyperinsulinism and sex hormones in young adult African Americans Metabolism 1999 48: 107–112.
Ioffe E, Moon B, Connolly E, Friedman JM . Abnormal regulation of the leptin gene in the pathogenesis of obesity Proc Natl Acad Sci USA 1998 95: 11852–11857.
Luke AH, Rotimi CN, Cooper RS, Long AE, Forrester TE, Wilks R, Bennett FI, Ogunbiyi O, Compton JA, Bowsher RR . Leptin and body composition of Nigerians, Jamaicans, and US blacks Am J Clin Nutr 1998 67: 391–396.
Acknowledgements
The technical assistance of Lenette Pedersen and Dorte Phillip is gratefully appreciated. This work was supported by Fonden til lægevidenskabens Fremme, Danish Medical Research Council, Novo Nordic Foundation, The Aarhus University–Novo Nordisk Centre for Research in Growth and Regeneration and The Danish Diabetes Association.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kristensen, K., Pedersen, S. & Richelsen, B. Interactions between sex steroid hormones and leptin in women. Studies in vivo and in vitro. Int J Obes 24, 1438–1444 (2000). https://doi.org/10.1038/sj.ijo.0801428
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0801428
Keywords
This article is cited by
-
Plasma leptin levels are related to body composition, sex, insulin levels and the A55V polymorphism of the UCP2 gene
International Journal of Obesity (2007)
-
Plasma levels of leptin and mammographic density among postmenopausal women: a cross-sectional study
Breast Cancer Research (2006)
-
Determinants of serum leptin levels in healthy postmenopausal women
Journal of Endocrinological Investigation (2003)