Fertility and Sterility
Volume 81, Issue 2 , Pages 398-402 , February 2004

Serum pattern of circulating free leptin, bound leptin, and soluble leptin receptor in the physiological menstrual cycle

Presented in part at the 15th Annual Meeting of the European Society of Human Reproduction and Embryology, June 27–30, 1999, Tours, France.

  • Franz Geisthövel, M.D.

      Affiliations

    • Center for Gynecological Endocrinology and Reproductive Medicine, Freiburg im Breisgau, Freiburg i. Br., Germany
    • Corresponding Author InformationReprint requests: Franz Geisthövel, M.D., Center for Gynecological Endocrinology and Reproductive Medicine Freiburg, Kaiser-Josephstrasse 168, D-79098, Freiburg i. Br., Germany (FAX: 49-0761-32111).
    • ,
  • Nicoline Jochmann, M.D.

      Affiliations

    • Department of Cardiology and Angiology, Charité/Campus-Mitte, Berlin, Germany
    • ,
  • Adji Widjaja, M.D.

      Affiliations

    • Department of Gastroenterology, Hepatology, and Endocrinology, University Medical School, Hannover, Germany
    • ,
  • Rüdiger Horn, B.Sc.

      Affiliations

    • Department of Gastroenterology, Hepatology, and Endocrinology, University Medical School, Hannover, Germany
    • ,
  • Georg Brabant, M.D.

      Affiliations

    • Department of Gastroenterology, Hepatology, and Endocrinology, University Medical School, Hannover, Germany

Received 3 February 2003 ,Revised 19 June 2003 ,Accepted 19 June 2003.

References 

  1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432
  2. Karlsson C, Lindell K, Svensson E, Bergh C, Lind P, Billig H, et al.  Expression of functional leptin receptors in the human ovary. J Clin Endocrinol Metabol. 1997;82:4144–4148
  3. Antzak M, van Blerkom J. Oocyte influences on early development (the regulatory proteins leptin and STAT3 are polarized in mouse and human oocytes and differentially distributed within the cells of the preimplantation stage embryo). Mol Hum Reprod. 1997;3:1067–1086
  4. Butte NF, Hopkinson JM, Nicolson MA. Leptin in human reproduction (serum leptin levels in pregnant and lactating women). J Clin Endocrinol Metabol. 1997;82:585–589
  5. Chehab FF, Mounzih K, Lu R, Lim ME. Early onset of reproductive function in normal female mice treated with leptin. Science. 1997;275:88–90
  6. Cheung CC, Thornton JE, Kuijper JL, Weigle DS, Clifton DK, Steiner RA. Leptin is a metabolic gate for the onset of puberty in the female rat. Endocrinology. 1997;138:855–858
  7. Licino J, Mantzoros C, Negrao AB, Cizza G, Wong M, Bongiomo PB, et al.  Human leptin levels are pulsatile and inversely related to pituitary-adrenal Function. Nat Med. 1997;3:575–579
  8. Sinha MK, Sturis J, Ohannesian J, Magosin S, Stephens TW, Heiman ML, et al.  Ultradian oscillations of leptin secretion in humans. Biochem Biophys Res Commun. 1996;228:733–738
  9. Licino J, Negrao AB, Mantzoros C, Kaklamani V, Wong M, Bongiorno PB, et al.  Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. Proc Natl Acad Sci USA. 1998;95:2541–2546
  10. Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S, et al.  Nocturnal rise of leptin in lean, obese, and non–insulin-dependent diabetes mellitus subjects. J Clin Invest. 1996;97:1344–1347
  11. Geisthövel F, Meysing A, Brabant G. C-peptide and insulin, but not C19-steroids, support the predictive value of body mass index on leptin in serum of premenopausal women. Hum Reprod. 1998;13:547–553
  12. Hardie L, Trayhurn P, Abramovich D, Fowler P. Circulating leptin in women (a longitudinal study on the menstrual cycle and during pregnancy). Clin Endocrinol. 1997;47:101–106
  13. Mannucci E, Ognibene A, Becorpi A, Cremasco F, Pellegrini S, Ottanelli S, et al.  Relationship between leptin and oestrogens in healthy women. Eur J Endocrinol. 1998;139:198–201
  14. Messinis IE, Milingos S, Zikopoulos K, Kollios G, Seferiadis K, Lolis D. Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone. Hum Reprod. 1998;13:1152–1156
  15. Shimizu H, Shimomura Y, Nakanishi Y, Futawatari T, Ohtani K, Sato N, et al.  Estrogen increases in vivo leptin production in rats and human subjects. Endocrinology. 1997;154:285–292
  16. Tataranni PA, Monroe MB, Dueck CA. Adiposity, plasma concentration and reproductive function in active and sedentary females. Int J Obes. 1997;21:818–821
  17. 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
  18. Diamond FB, Eichler DC, Duckett G, Jorgensen EV, Shulman D, Root AW. Demonstration of a leptin binding factor in human serum. Biochem Biophys Res Commun. 1997;233:818–822
  19. Houseknecht KL, Mantzoros CS, Kuliawat R, Hadro E, Flier JS, Kahn BB. Evidence for leptin binding to proteins in serum of rodents and humans (modulation with obesity). Diabetes. 1996;45:1638–1643
  20. Sinha MK, Opentanova I, Ohannesian JP, Kolaczynski JW, Heiman ML, Hale J, et al.  Evidence of free and bound leptin in human circulation (studies in lean and obese subjects and during short-term fasting). J Clin Invest. 1996;98:1277–1282
  21. Horn R, Geldszus R, Pötter E, von zur Mühlen A, Brabant G. Radioimmunassay for the detection of leptin in human serum. Exp Clin Endocrinol Diabetes. 1996;104:454–458
  22. Lewandowski K, Horn R, O'Callaghan CJ, Dunlop D, Medley GF, O'Hare P, et al.  Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies. J Clin Endocrinol Metabol. 1999;84:300–306
  23. Kolaczynski JW, Ohannesian J, Considine RV, Marco CC, Caro JF. Responses of leptin to short-term and prolonged overfeeding in humans. J Clin Endocrinol Metabol. 1996;81:4162–4165
  24. Kohrt WM, Landt M, Birge SJ. Serum leptin levels are reduced in response to exercise training, but not hormone replacement therapy, in older women. J Clin Endocrinol Metabol. 1996;81:3980–3985
  25. Laughlin GA, Yen SSC. Hypoleptinemia in women athletes (absence of a diurnal rhythm with amenorrhea). J Clin Endocrinol Metabol. 1997;82:318–321
  26. Havel PJ, Kasim-Karakas S, Mueller W, Johnson PR, Gingerich RL, Stern JS. Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women (effects of dietary fat content and sustained weight loss). J Clin Endocrinol Metabol. 1996;81:4406–4413
  27. Grinspoon S, Gulick T, Askari H, Landt M, Lee K, Anderson E, et al.  Serum leptin levels in women with anorexia nervosa. J Clin Endocrinol Metabol. 1996;81:3861–3863
  28. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, et al.  Leptin levels in human and rodent (measurement of plasma leptin and obRNA in obese and weight-reduced subjects). Nat Med. 1995;1:1155–1161
  29. Mantzoros CS, Flier JS, Rogol AD. A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metabol. 1997;82:1066–1070
  30. Quinton ND, Smith RF, Clayton PE, Gill MS, Shalet S, Justice SK, et al.  Leptin binding activity changes with age (the link between leptin and puberty). J Clin Endocrinol Metabol. 1999;84:2336–2341
  31. Gavrilova O, Barr V, Marcus-Samuels B, Reitman M. Hyperleptinemia of pregnancy associated with the appearance of a circulating form of the leptin receptor. J Biol Chem. 1997;272:30546–30551
  32. Tartaglia LA, Dembski M, Wenig X, Deng N, Culpepper J, Devos R, et al.  Identification and expression cloning of a leptin receptor, Ob-R. Cell. 1995;83:1263–1271
  33. Baumann G. Growth hormone binding to a circulating receptor fragment—the concept of receptor shedding and receptor splicing. Exp Clin Endocrinol Diabetes. 1995;103:2–6
  34. Müller-Newen G, Köhne C, Heinrich PC. Soluble receptors for cytokines and growth factors. Int Arch Allergy Immunol. 1996;111:99–106
  35. Baxter RC. Insulin-like growth factor binding proteins in human circulation (a review). Horm Res. 1994;42:140–144
  36. Heaney ML, Golde DW. Soluble hormone receptors. Blood. 1993;82:1945–1948
  37. Giudice LC. The insulin-like growth factor system in normal and abnormal human ovarian follicle development. Am J Med. 1995;98:48–54
  38. Bonner JC, Brody AR. Cytokine-binding proteins in the lung. Am J Physiol. 1995;12:L869–878
  39. Jockenhövel F, Blum WF, Vogel E, Englaro P, Müller-Wieland D, Reinwein D, et al.  Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men. J Clin Endocrinol Metabol. 1997;82:2510–2513
  40. Palmert MP, Radovick S, Boepple PA. The impact of reversible gonadal sex steroid suppression on serum leptin concentrations in children with central precocious puberty. J Clin Endocrinol Metabol. 1998;83:1091–1096
  41. Rouru J, Anttila L, Koskinen P, Penttilä T, Irjala K, Huupponen R, et al.  Serum leptin concentrations in women with polycystic ovary syndrome. J Clin Endocrinol Metabol. 1997;82:1697–1700
  42. Lönnqvist F, Arner P, Nordfors L, Schalling M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med 1:950–3
  43. Saad MF, Damani S, Gingerich RL, Riad-Gabriel MG, Khan A, Boyadjian R, et al.  Sexual dimorphism in plasma leptin concentration. J Clin Endocrinol Metabol. 1997;82:579–584
  44. Schwartz MW, Peskind E, Raskind M, Boyko EJ, Porte D. Cerebrospinal fluid leptin levels (relationship to plasma levels and to adiposity in humans). Nat Med. 1996;2:589–593
  45. Rosenbaum M, Nicolson M, Hirsch J, Heymsfield SB, Gallagher D, Chu F, et al.  Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metabol. 1996;81:3424–3427
  46. Bützow TL, Moilanen JM, Lehtovirta M, Tuomi T, Hovatta O, Siegberg R, et al.  Serum and follicular fluid leptin during in vitro fertilization (relationship among leptin increase, body fat mass, and reduced ovarian response). J Clin Endocrinol Metabol. 1999;84:3135–3139
  47. Agarwal SK, Vogel K, Weitsman SR, Magoffin DA. Leptin antagonizes the insulin-like growth-factor-I augmentation of steroidgenesis in granulosa and theca cells of human ovary. J Clin Endocrinol Metabol. 1999;84:1072–1076

☆ This study was supported financially by Ferring Arzneimittel GmbH, Organon GmbH, and Serono Pharma GmbH, Germany.

PII: S0015-0282(03)02719-5

doi: 10.1016/j.fertnstert.2003.06.020

Fertility and Sterility
Volume 81, Issue 2 , Pages 398-402 , February 2004

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