Leptin and Pubertal Development in Humans

  • Susann Blüher
  • Christos S. Mantzoros

Abstract

Since the discovery of leptin through positional cloning of the ob gene (Zhang et al., 1994) more than 8 years ago, extensive research efforts have focused on the biology and physiology of this hormone. Leptin is a 167-amino acid protein that is structurally related to members of the long-chain helical cytokine family (Madej et al., 1995; Zhang et al., 1997). It is expressed primarily in white adipose tissue (Maffei et al., 1995; Klein et al., 1996; Leroy et al., 1996). Leptin expression has also been detected in the stomach (Bado et al., 1998), hypothalamus (Morash et al., 1999), pituitary (Jin et al., 2000), skeletal muscle (Wang et al., 1998) placenta (Masuzaki et al., 1997), mammary gland (Smith-Kirwin et al., 1998; Aoki et al., 1999), and possibly in brown fat.

Keywords

Obesity Estrogen Cortisol Testosterone Cocaine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agarwal, S. K., Vogel, K., Weitsman, S. R., and Magoffin, D. A. (1999). Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulosa and theca cells of the human ovary. J. Clin. Endocrinol. Metab., 84 1072–1076.PubMedCrossRefGoogle Scholar
  2. Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., and Flier, J. S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature, 382, 250–252.PubMedCrossRefGoogle Scholar
  3. Ahima, R. S., Dushay, J., Flier, S. N., Prabakaran, D., and Flier, J. S. (1997). Leptin accelerates the timing of puberty in normal female mice. J. Clin. Invest., 99, 391–395.PubMedCrossRefGoogle Scholar
  4. Aoki, N., Kawamura, M., and Matsuda, T. (1999). Lactation-dependent down regulation of leptin production in mouse mammary gland. Biochim. Biophys. Acta, 1427, 298–306.PubMedCrossRefGoogle Scholar
  5. Argiolas, A., Melis, M. R., Murgia, S., and Schioth, H. B. (2000). ACTH- and alpha-MSH-induced grooming, stretching, yawning, and penile erection in male rats: sites of action in the brain and role of melanocortin receptors. Brain Res. Bull., 51, 425–431.PubMedCrossRefGoogle Scholar
  6. Audi, L., Mantzoros, C. S., Vidal-Puig, A., Vargas, D., Gussinye, M., and Carrascosa, A. (1998). Leptin in relation to resumption of menses in women with anorexia nervosa. Mol. Psychiatry, 3, 544–547.PubMedCrossRefGoogle Scholar
  7. Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J. P., Bortoluzzi, M. N., Moizo, L., Lehy, Th., Guerre-Millo, M., Le Marchand-Brustel, Y., and Lewin, M. J. M. (1998). The stomach is a source of leptin. Nature, 394, 790–793.PubMedCrossRefGoogle Scholar
  8. Ballauff, A., Ziegler, A., Emons, G., Sturm, G., Blum, W. F., Remschidt, H., and Hebebrand, J. (1999). Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain. Mol. Psychiatry, 4, 71–75.PubMedCrossRefGoogle Scholar
  9. Barash, I. A., Cheung, C. C., Weigle, D. S., Ren, H., Kabigting, E. B., Kuijper, J. L., Clifton, D. K., and Steiner, R. A. (1996). Leptin is a metabolic signal to the reproductive system. Endocrinology, 137, 3144–3147.PubMedCrossRefGoogle Scholar
  10. Barkan, D., Jia, H., Dantes, A., Vardimon, L., Amsterdam, A., and Rubinstein, M. (1999). Leptin modulates the glucocorticoid-induced ovarian steroidogenesis. Endocrinology, 140, 1731–1738.PubMedCrossRefGoogle Scholar
  11. Blum, W. F., Englaro, P., Hanitsch, S., Juul, A., Hertel, N. T., Kiess, W., Skakkebaek, N. E., Birkett, M., Heiman, M., Attanasio, A., and Rascher, W. (1997). Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J. Clin. Endocrinol. Metab., 82, 2904–2910.PubMedCrossRefGoogle Scholar
  12. Bouvattier, C., Lahlou, N., Roger, M., and Bougneres, P. (1998). Hyperleptinemia is associated with impaired gonadotrophin response to GnRH during late puberty in obese girls, not boys. Eur. J. Endocrinol., 138, 653–658.PubMedCrossRefGoogle Scholar
  13. Brannian, J. D., Zhao, Y., and McElroy, M. (1999). Leptin inhibits gonadotrophin-stimulated granulosa cell progesterone production by antagonizing insulin action. Hum. Rep rod., 14, 1445–1448.PubMedCrossRefGoogle Scholar
  14. Bray, G. A. (1997). Obesity and reproduction. Hum. Reprod., 12, 26–32.PubMedCrossRefGoogle Scholar
  15. Cameron, J. L. (1997). Search for the signal that conveys metabolic status to the reproductive axis. Curr. Opin. Endocrinol. Diabetes, 4, 158–163.CrossRefGoogle Scholar
  16. Cantopher, T., Evans, C, Lacey, J. H., and Pearce, J. M. (1988). Menstrual and ovulatory disturbance in bulimia. BMJ, 297, 836–837.PubMedCrossRefGoogle Scholar
  17. Castracane, V. D., Kraemer, R. R., Franken, M. A., Kraemer, G. R., and Gimpel, T. (1998). Serum leptin concentration in women: effect of age, obesity, and estrogen administration. Fertil. Steril., 70(3), 472–477.PubMedCrossRefGoogle Scholar
  18. Caprio, M., Isidori, A. M., Carta, A. R., Moretti, C., Dufau, M. L., and Fabbri, A. (1999). Expression of functional leptin receptors in rodent Leydig cells. Endocrinology, 140, 4939–4947.PubMedCrossRefGoogle Scholar
  19. Chebab, F., Lim, M., and Lu, R. (1996a). Correction of the sterility defect in homozygous obese female mice by treatment with human recombinant leptin. Nat. Genet., 12, 318–320.CrossRefGoogle Scholar
  20. Chebab, F. F., Mounzih, K., Lu, R., and Lim, M. E. (1996b). Early onset of reproductive function in normal mice treated with leptin. Science, 275, 88–90.CrossRefGoogle Scholar
  21. Christou, H., Connors, J. M., Ziotopoulou, M., Hatzidakis, V., Papathanassoglou, E., Ringer, S. A., and Mantzoros, C. S. (2001). Cord blood leptin and insulin-like growth factor levels are independent predictors of fetal growth. J. Clin. Endocrinol. Metab., 86, 935–938.PubMedCrossRefGoogle Scholar
  22. Cioffi, J. A., Shafer, A. W., Zupanicic, T. J., Smih-Gbur, J., Mikhail, A., Platika, D., and Snodgrass, H. R. (1996). Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat. Med., 2, 585–589PubMedCrossRefGoogle Scholar
  23. Cioffi, J. A., Van Blerkom, J., Antczak, M., Shafer, A., Wittmer, S., and Snodgrass, H. R. (1997). The expression of leptin and its receptors in pre-ovulatory human follicles. Mol. Hum. Reprod., 3, 467–472.PubMedCrossRefGoogle Scholar
  24. Clayton, P. E., Gill, M. S., Hall, C. M., Tillmann, V., Whatmore, A. J., and Price, D. A. (1997). Serum leptin through childhood and adolescence. Clin. Endocrinol., 46(6), 727–733.CrossRefGoogle Scholar
  25. Clement, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J. M., Basdevant, A., Bougneres, P., Lebouc, Y., Froguel, P., and Guy-Grand, B. (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature, 392, 398–401.PubMedCrossRefGoogle Scholar
  26. Cunningham, M. J., Clifton, D. K., and Steiner, R. A. (1999). Leptin’s actions on the reproductive axis: perspectives and mechanisms. Biol. Reprod., 60, 216–222.PubMedCrossRefGoogle Scholar
  27. Duggal, P. S., Van Der Hoek, K. H., Milner, C. R., Ryan, N. K., Armstrong, D. T., Magoffin, D. A., and Norman, R. J. (2000). The in vivo and in vitro effects of exogenous leptin on ovulation in the rat. Endocrinology, 141, 1971–1976.PubMedCrossRefGoogle Scholar
  28. Erickson, J. C., Ahima, R. S., Hollopeter, G., Flier, J. S., and Palmiter, R. D. (1997). Endocrine function of neuropeptide Y knockout mice. Regul. Pept., 70, 199–202.PubMedCrossRefGoogle Scholar
  29. Ellis, K. J. and Nicolson, M. (1997). Leptin levels and body fatness in children: effects of gender, ethnicity, and sexual development. Pediatr. Res., 42, 484–488.PubMedCrossRefGoogle Scholar
  30. Farooqi, I. S., Jebb, S. A., Langmack, G., Lawrence, E., Cheetham, C. H., Prentice, A. M., Hughes, I. A., McCamish, M. A., and O’Rahilly, S. (1999). Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N. Engl. J. Med., 341, 879–884.PubMedCrossRefGoogle Scholar
  31. Frisch, R. E. and Revelle, R. (1970). Height and weight at menarche and a hypothesis of critical body weights and adolescent events. Science, 169, 397–399.PubMedCrossRefGoogle Scholar
  32. Frisch, R. E. (1980). Pubertal adipose tissue: it is necessary for normal sexual maturation? Evidence from the rat and human female. Fed. Proc., 39, 2395–2400.PubMedGoogle Scholar
  33. Gill, M. S., Hall, C. M., Tillmann, V., and Clayton, P. E. (1999). Constitutional delay in growth and puberty (CDGP) is associated with hypoleptinemia. J. Clin. Endocrinol. Metab., 50, 721–736.Google Scholar
  34. Grinspoon, S., Gulick, T., Askari, H., Landt, M., Lee, K., Anderson, E., Ma, Z., Vignati, L., Bowsher, R., Herzog, D., and Klibanski, A. (1996). Serum leptin levels in women with anorexia nervosa. J. Clin. Endocrinol. Metab., 81, 3861–3863.PubMedCrossRefGoogle Scholar
  35. Hassink, S. G., Sheslow, D. V., de Lancey, E., Opentanova, I., Considine, R. V., and Caro, J. F. (1996). Serum leptin in children with obesity: relationship to gender and development. Pediatrics, 98, 201–203.PubMedGoogle Scholar
  36. Havel, P. J., Kasim-Karakas, S., Dubuc, G. R., Mueller, W., and Phinney, S. D. (1996). Gender differences in plasma leptin concentrations. Nat. Med., 2, 949–950.PubMedCrossRefGoogle Scholar
  37. Heger, S., Partsch, C. J., Peter, M., Blum, W. F., Kiess, W., and Sippell, W. (1999). Serum leptin levels in patients with progressive central precocious puberty. Pediatr. Res., 46, 71–75.PubMedCrossRefGoogle Scholar
  38. Henson, M. C. and Castracane, V. D. (2000). Leptin in pregnancy. Biol. Reprod., 63(5), 1219–1228.PubMedCrossRefGoogle Scholar
  39. Henson, M. C., Castracane, V. D., O’Neil, J. S., Gimpel, T., Swan, K. F., Green, A. E., and Shi, W. (1999). Serum leptin concentrations and expression of leptin transcripts in placental trophoblast with advancing baboon pregnancy. J. Clin. Endocrinol. Metab., 84, 2543–2549.PubMedCrossRefGoogle Scholar
  40. Heretier, A., Charnay, Y., and Aubert, M. L. (1997). Regional distribution of mRNA encoding the long form of receptor in mouse brain. Neurosci. Res. Commun., 21, 113–118.CrossRefGoogle Scholar
  41. Hileman, S. M., Pierroz, D. D., and Flier, J. S. (2000). Leptin, nutrition, and reproduction: timing is everything. J. Clin. Endocrinol. Metab., 85, 804–807.PubMedCrossRefGoogle Scholar
  42. Hislop, M. S., Ratanjee, B. D., Soule, S. G., and Marais, A. D. (1999). Effects of anabolic-androgenic steriod use or gonadal testosterone suppression on serum leptin concentration in men. Eur. J. Endocrinol., 141, 40–46.PubMedCrossRefGoogle Scholar
  43. Hohmann, J. G., Teal, T. H., Clifton, D. K., Davis, J., Hruby, V. J., Han. G., and Steiner, R. (2000). Differential role of melanocortins in mediating leptin’s central effects on feeding and reproduction. Am. J. Physiol. Regul. Integr. Comp. Physiol., 278, R50–59.PubMedGoogle Scholar
  44. Horlick, M. B., Rosenbaum, R. V., Nicolson, M., Levine, L. S., Fedun, B., Wang, J., Pierson, R. N., Jr., and Leibel, R. L. (2000). Effect of puberty on the relationship between circulating leptin and body composition. J. Clin. Endocrinol. Metab., 85, 2509–2518.PubMedCrossRefGoogle Scholar
  45. Huang, X. F., Lin, S., and Zhang, R. (1997). Upregulation of leptin receptor mRNA expression in obese mouse brain. Neuroreport, 8, 1035–1038.PubMedCrossRefGoogle Scholar
  46. Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeir, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., Smith, F. J., Campfield, L. A., Burn, P., and Lee, F. (1997). Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell, 88, 131–141.PubMedCrossRefGoogle Scholar
  47. Iqbal, J., Pompolo, S., Considine, R. V., and Clarke, I. J. (2000). Localization of leptin receptor-like immunoreactivity in the corticotropes, somatotropes, and gonadotropes in the ovine anterior pituitary. Endocrinology, 141, 1515–1520.PubMedCrossRefGoogle Scholar
  48. Jakacki, R. I., Kelch, R. D., Saunder, S. E., Lloyd, J. S., Hopwood, J. N., and Marshall, J. C. (1982). Pulsatile secretion of luteinizing hormone in children. J. Clin. Endocrinol. Metab., 55, 453–458.PubMedCrossRefGoogle Scholar
  49. Jaruratanasirikul, S., Mosuwan, L., and Lebel, L. (1997). Growth pattern and age at menarche of obese girls in a transitional society. J. Pediatr. Endocrinol. Metab., 10, 487–490.PubMedCrossRefGoogle Scholar
  50. Jimerson, D. C., Mantzoros, C., Wolfe, B. E., and Metzger, E. D. (2000). Decreased serum leptin in bulimia nervosa. J. Clin. Endocrinol. Metabol., 85, 4511–4514.CrossRefGoogle Scholar
  51. Jin, L., Zhang, S., Burguera, B. G., Couce, M. E., Osamura, R. Y., Kulig, E., and Lloyd, R. V. (2000). Leptin and leptin receptor expression in rat and mouse pituitary cells. Endocrinology, 141, 333–339.PubMedCrossRefGoogle Scholar
  52. Jureus, A., Cunningham, M. J., McClain, M. E., Clifton, D. K., and Steiner, R. A. (2000). Galanin-like peptide (GALP) is a target for regulation by leptin in the hypothalamus of the rat. Endocrinology, 141, 2703–2706.PubMedCrossRefGoogle Scholar
  53. Karlsson, C., Lindell, K., Svensson, E., Bergh, C., Lind, P., Billig, H., Carlsson, L. M., and Carlsson, B. (1997). Expression of functional leptin receptors in the human ovary. J. Clin. Endocrinol. Metab., 82, 4144–4148.PubMedCrossRefGoogle Scholar
  54. Kennedy, G. C. and Mitra, J. (1963). Body-weight and food intake as initiating factors for puberty in the rat. J.Physiol., 766, 375–381.Google Scholar
  55. Kiess, W., Englaro, P., Hanitsch, S., Rascher, W., Attanasio, A., and Blum, W. F. (1996). High leptin concentrations in serum of very obese children are further stimulated by dexamethasone. Horm. Metabol. Res., 28, 708–710.CrossRefGoogle Scholar
  56. Kiess, W., Siebler, T., Englaro, P., Kratzsch, J., Deutsch, J., Meyer, K., Gallaher, B., and Blum, W. F. (1998). Leptin as a metabolic regulator during fetal and neonatal life and in childhood and adolescence. J. Pediatr. Endocrinol. Me tab., 11, 1–13.CrossRefGoogle Scholar
  57. Kiess, W., Reich, A., Meyer, K., Glasow, A., Deutsch, J., Klammt, J., Yang, Y., Müller, G., and Kratzsch, J. (1999). A role for leptin in sexual maturation and puberty? Horm. Res., 51, 55–63.PubMedCrossRefGoogle Scholar
  58. Kiess, W., Müller, G., Galler, A., Reich, A., Deutscher, J., Klammt, J., and Kratzsch, J. (2000). Body fat mass, leptin and puberty. J. Pediatr. Endocrinol. Metab., 13, 717–722.PubMedCrossRefGoogle Scholar
  59. Kitawaki, J., Kusuk, I., Koshiba, H., Tsukamoto, K., and Honjo, H. (1999). Leptin directly stimulates aromatase activity in human luteinized granulosa cells. Mol. Hum. Reprod., 5, 708–713.PubMedCrossRefGoogle Scholar
  60. Klein, S., Coppack, S. W., Mohamed Ali, V., and Landt, M. (1996). Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes, 45, 984–987.PubMedCrossRefGoogle Scholar
  61. Lado-Abeal, J., Lukyuanenko, Y. O., Swamy, S., Hermida, R. C., Hutson, J. C., and Norman, R. L. (1999). Short-term leptin infusion does not affect circulating levels of LH, testosterone or cortisol in food-restricted pubertal males rhesus macaques. Clin. Endocrinol., 51(1), 41–51.CrossRefGoogle Scholar
  62. Lahlou, N., Landais, P., De Boissieu, D., and Bougneres, P. F. (1997). Circulating leptin in normal children and during the dynamic phase of juvenile obesity: relation to body fatness, energy metabolism, caloric intake and sexual dimorphism. Diabetes, 46, 989–993.PubMedCrossRefGoogle Scholar
  63. Laughlin, G. A. and Yen, S. S. (1996). Nutritional and endocrine-metabolic aberrations in amenorrheic athletes. J. Clin. Endocrinol. Metab., 81, 4301–4309.PubMedCrossRefGoogle Scholar
  64. Laughlin, G. A. and Yen, S. S. (1997). Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea. J. Clin. Endocrinol. Metab., 82, 318–321.PubMedCrossRefGoogle Scholar
  65. Lebrethon, M. C., Vandersmissen, E., Gerard, A., Parent, A. S., Junien, J. L., and Bourguignon, J. P. (2000a). In vitro stimulation of the pre-pubertal rat gonadotropin-releasing hormone pulse generator by leptin and neuropeptide Y through distinct mechanisms. Endocrinology, 141, 1464–1469.PubMedCrossRefGoogle Scholar
  66. Lebrethon, M. C., Vandersmissen, E., Gerard, A., Parent, A. S., and Bourguignon, J. P. (2000b). Cocaine and amphetamine-regulated-transcript peptide mediation of leptin stimulatory effect on the rat gonadotropin-releasing hormone pulse generator in vitro. J. Neuroendocrinol., 12, 383–385.PubMedCrossRefGoogle Scholar
  67. Leroy, P., Dessolin, S., Villageois, P., Moon, B. C., Friedman, J. M., Ailhaud, G., and Dani, C. (1996). Expression of ob gene in adipose cells. Regulation by insulin. J. Biol. Chem., 271, 2365–2368.PubMedCrossRefGoogle Scholar
  68. Licinio, J., Mantzoros, C., Negrao, A. B., Cizza, G., Wong, M. L., Bongiorno, P. B., Chrousos, G. P., Karp, B., Allen, C, Flier, J. S., and Gold, P. W. (1997). Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat. Med., 3, 575–579.PubMedCrossRefGoogle Scholar
  69. Licinio, J., Negrao, A. B., Mantzoros, C., Kaklamani, V., Wong, M. L., Bongiorno, P. B., Mulla, A., Cearnal, L., Veldhuis, J. D., Flier, J. S., McCann, S. M., and Gold, P. W. (1998a). Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. Proc. Natl. Acad. Sci. USA, 95(5), 2541–2546.PubMedCrossRefGoogle Scholar
  70. Licinio, J., Negrao, A. B., Mantzoros, C., Kaklamani, V., Wong, M. L., Bongiorno, P. B., Negro, P. P., Mulla, A., Veldhuis, J. D., Cearnal, L., Flier, J. S., and Gold, P. W. (1998b). Sex differences in circulating human leptin pulse amplitude: Clinical implications. J. Clin. Endocrinol. Metab., 83, 4140–4147.PubMedCrossRefGoogle Scholar
  71. Luukkaa, V, Rouru, J., Ahokoski, O., Scheinin, H., Irjala, K., and Huupponen, R. (2000). Acute inhibition of oestrogen biosynthesis does not affect serum leptin levels in young men. Eur. J. Endocrinol., 142, 164–169.PubMedCrossRefGoogle Scholar
  72. MacConnie, S. E., Barkan, A., and Lampman, R. M. (1986). Decreased hypothalamic gonadotropin-releasing hormone secretion in male marathon runners. N. Engl. J. Med., 315, 411–417.PubMedCrossRefGoogle Scholar
  73. Madej, T., Boguski, M. S., and Bryant, S. H. (1995). Threading analysis suggests that the obese gene product may be a helical cytokine. FEBS Lett., 373, 13–18.PubMedCrossRefGoogle Scholar
  74. Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., Kern, P. A., and Friedman, J. M. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat. Med., 1, 1155–1161.PubMedCrossRefGoogle Scholar
  75. Mann, D. R., Akinbami, M. A., Gould, K. G., and Castracane, V. D. (2000). A longitudinal study of leptin during development in the male rhesus monkey: the effect of body composition and season on circulating leptin levels. Biol. Reprod., 62, 285–291.PubMedCrossRefGoogle Scholar
  76. Mantzoros, C. S., Flier, J. S., and Rogol, A. D. (1997a). A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. Rising leptin levels may signal the onset of puberty. J. Clin. Endocrinol. Metab., 82, 1066–1070.PubMedCrossRefGoogle Scholar
  77. Mantzoros, C. S., Varvarigou, A., Kaklamani, V. G., Beratis, N. G., and Flier, J. S. (1997b). Effect of birth weight and maternal smoking on cord blood leptin concentrations of full-term and preterm newborns. J. Clin. Endocrinol. Metab., 82, 2856–2861.PubMedCrossRefGoogle Scholar
  78. Mantzoros, C., Flier, J. S., Lesem, M. D., Brewerton, T. D., and Jimerson, D. C. (1997c). Cerebrospinal fluid leptin in anorexia nervosa: correlation with nutritional status and potential role in resistance to weight gain. J. Gin. Endocrinol. Metab., 82, 1845–1851.CrossRefGoogle Scholar
  79. Mantzoros, C. S. (1999). The role of leptin in human obesity and disease: a review of current evidence. Ann. Intern. Med., 130, 671–680.PubMedGoogle Scholar
  80. Mantzoros, C. S., Ozata, M., Negrao, A. B., Suchard, M. A., Ziotopoulou, M., Caglayan, S., Elashoff, R. N., Cogswell, R. J., Negro, P., Liberty, V., Wong, M., Veldhuis, J., Ozdemir, I. C., Gold, P. W., Flier, J. S., and Licinio, J. (2001). Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and lepdn-deficient subjects: evidence for possible partial TSH regulation by leptin in humans. J. Gin. Endocrinol. Metab., 86, 3284–3291.CrossRefGoogle Scholar
  81. Marshall, W. A. and Tanner, J. M. (1969). Variations in the pattern of pubertal changes in girls. Arch. Dis. Child., 44(235), 291–303.PubMedCrossRefGoogle Scholar
  82. Marshall, W. A. and Tanner, J. M. (1970). Variations in the pattern of pubertal changes in boys. Arch. Dis. Child., 45(239), 13–23.PubMedCrossRefGoogle Scholar
  83. Masuzaki, H., Ogawa, Y., Sagawa, N., Hosoda, K., Matsumoto, T., Mise, H., Nishimura, H., Yoshimasa, Y., Tanaka, I., Mori, T., and Nakao, K. (1997). Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat. Med., 3, 1029–1033.PubMedCrossRefGoogle Scholar
  84. Matkovic, V., Ilich, J. Z., Badenhop, N. E., Skugor, M., Clairmont, A., Klisovic, D., and Landoll, J. D. (1997a). Gain in body fat is inversely related to the nocturnal rise in serum leptin levels in young females. J. Clin. Endocrinol. Metab., 82, 1368–1372.PubMedCrossRefGoogle Scholar
  85. Matkovic, V, Ilich, J. Z., Skugor, M., Badenhop, N. E., Goel, P., Clairmont, A., Klisovic, D., Nahhas, R. W., and Landoll, J. D. (1997b). Leptin is inversely related to age at menarche in human females. J. Clin. Endocrinol. Metab., 82, 3239–3245.PubMedCrossRefGoogle Scholar
  86. Matsuda, J., Yokota, I., Iida, M., Murakami, T., Naito, E., Ito, M., Shima, K., and Kuroda, Y. (1997). Serum leptin concentration in cord blood: relationship to birth weight and gender. J. Gin. Endocrinol. Metab., 82, 1642–1644.CrossRefGoogle Scholar
  87. Matsuoka, N., Ogawa, Y., Hosoda, K., Matsuda, J., Masuzaki, H., Miyawaki, T., Azuma, N., Natsui, K., Nishimura, H., Yoshimasa, Y., Nishi, S., Thompson, D. B., and Nakao, K. (1997). Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity. Diabetologia, 40, 1204–1210.PubMedCrossRefGoogle Scholar
  88. Mauras, N., Rogol, A. D., Haymond, M. W., and Veldhuis, J. (1996). Sex steroids, growth hormone, insulin-like growth factor-1: neuroendocrine and metabolic regulation in puberty. Horm. Res., 45, 74–80.PubMedCrossRefGoogle Scholar
  89. Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., Cheetham, C. H., Earley, A. R., Barnett, A. H., Prins, J. B., and O’Rahilly, S. (1997). Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature, 387, 903–908.PubMedCrossRefGoogle Scholar
  90. Morash, B., Li, A., Murphy, P. R., Wilkinson, M., and Ur, E. (1999). Leptin gene expression in the brain and pituitary gland. Endocrinology, 140, 5995–5998.PubMedCrossRefGoogle Scholar
  91. Moschos, S., Chan, J. L., and Mantzoros, C. S. (2002). Leptin and reproduction: a review. Fertil. Steril, 77(3), 433–444.PubMedCrossRefGoogle Scholar
  92. Murray, J. F., Mercer, J. G., Adan, R. A., Datta, J. J., Aldairy, C., Moar, K. M., Baker, B. I., Stock, M. J., and Wilson, C. A. (2000). The effect of leptin on luteinizing hormone release is exerted in the zona incerta and mediated by melanin-concentrating hormone. J. Neuroendocrinol., 12, 1133–1139.PubMedCrossRefGoogle Scholar
  93. O’Neil, J. S., Green, A. E., Edwards, D. E., Swan, K. F., Gimpel, T., Castracane, V. D., and Henson, M. C. (2001). Regulation of leptin and leptin receptor in baboon pregnancy: effects of advancing gestation and fetectomy. J. Clin. Endocrinol. Metab., 86, 2518–2524.PubMedCrossRefGoogle Scholar
  94. Parent, A. S., Lebrethon, M. C., Gerard, A., Vandersmissen, E., and Bourguignon, J. P. (2000). Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y. Regul. Pept., 92, 17–24.PubMedCrossRefGoogle Scholar
  95. Plant, T. M. and Durant, A. R. (1997). Circulating leptin does not appear to provide a signal for triggering the initiation of puberty in the male rhesus monkey (Macaca mulatta). Endocrinology, 138, 4505–4508.PubMedCrossRefGoogle Scholar
  96. Quinton, N. D., Smith, R. F., Clayton, P. E., Gill, M. S., Shalet, S., Justice, S. K., Simon, S. A., Walters, S., Postel-Vinay, M.-C., Blakemore, A. I. F., and Ross, R. J. M. (1999). Leptin binding activity changes with age: the link between leptin and puberty. J. Clin. Endocrinol. Metab., 84, 2336–2341.PubMedCrossRefGoogle Scholar
  97. Roemmich, J. N., Clark, P. A., Berr, S. S., Mai, V., Mantzoros, C. S., Flier, J. S., Weltman, A., and Rogol, A. D. (1998). Gender differences in leptin levels during puberty are related to subcutaneous fat depot and sex steroids. Am. J. Physiol, 275, E543–E 551.PubMedGoogle Scholar
  98. Roemmich, J. N. and Rogol, A. D. (1999). Role of leptin during childhood growth and development. Endocrinol. Metab. Clin. North Am., 28(4), 749–758.PubMedCrossRefGoogle Scholar
  99. Saad, M. F., Riad-Gabriel, M. G., Khan, A., Sharma, A., Michael, R., Jinagouda, S. D., Boyadjian, R., and Steil, G. M. (1998). Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity. J. Clin. Endocrinol. Metab., 83, 453–459.PubMedCrossRefGoogle Scholar
  100. Schubring, C., Kiess, W., Englaro, P., Rascher, W., Dötsch, J., Hanitsch, S., Attanasio, A., and Blum, W. (1997). Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: relation to neonatal and placental weight. J. Clin. Endocrinol. Metab., 82, 1480–1483.PubMedCrossRefGoogle Scholar
  101. Schubring, C., Siebler, T., Englaro, P., Blum, W. F., Kratzsch, J., Triep, K., and Kiess, W. (1999). Rapid decline of leptin serum levels in healthy neonates after birth. Clin. Endocrinol., 51, 199–204.CrossRefGoogle Scholar
  102. Sinha, M. K., Ohannesian, J. P., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Magosin, S., Marco, C., and Caro, J. F. (1996a). Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J. Clin. Invest., 97, 1344–1347.PubMedCrossRefGoogle Scholar
  103. Sinha, M. K., Sturis, J., Ohannesian, J., Magosin, S., Stephens, T., Heiman, M. L., Polonsky, K. S., and Caro, J. F. (1996b). Ultradian oscillations of leptin secretion in humans. Biochem. Biophys. Res. Commun., 228, 733–738.PubMedCrossRefGoogle Scholar
  104. Sivan, E., Lin, W. M., Homko, C. J., Reece, E. A., and Boden, G. (1997). Leptin is present in human cord blood. Diabetes, 46, 917–919.PubMedCrossRefGoogle Scholar
  105. Smith-Kirwin, S. M., O’Connor, D. M., De Johnston, J., Lancey, E. D., Hassink, S. G., and Funanage, V. L. (1998). Leptin expression in human mammary epithelial cells and breast milk. J. Clin. Endocrinol. Metab., 83, 1810–1813.PubMedCrossRefGoogle Scholar
  106. Spicer, L. J. and Francisco, C. C. (1998). Adipose obese gene product, leptin, inhibits bovine ovarian thecal cell steroidogenesis. Biol. Reprod., 58, 207–212.PubMedCrossRefGoogle Scholar
  107. Strobel, A., Issad, T., Camoin, L., Ozata, M., and Strosberg, A. D. (1998). A leptin missense mutation associated with hypogonadism and morbid obesity. Nat. Genet., 18, 213–215.PubMedCrossRefGoogle Scholar
  108. Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., and Devos, R. (1995). Identification and cloning of a leptin receptor, OB-R. Cell, 83, 1263–1271.PubMedCrossRefGoogle Scholar
  109. Tartaglia, L. A. (1997). The leptin receptor. J. Biol. Chem., 272, 6093–6096.PubMedGoogle Scholar
  110. Terasawa, E. (1998). Cellular mechanism of pulsatile LHRH release. Gen. Comp. Endocrinol., 112, 283–295.PubMedCrossRefGoogle Scholar
  111. Urbanski, H. F. and Francis Pau, K.-Y. (1998). A biphasic developmental pattern of circulating leptin in the male rhesus macaque (Macaca mulatta). Endocrinology, 139(5), 2284–2286.PubMedCrossRefGoogle Scholar
  112. Varvarigou, A., Mantzoros, C. S., and Beratis, N. G. (1999). Cord blood leptin concentrations in relation to intrauterine growth. Clin. Endocrinol., 50, 177–183.CrossRefGoogle Scholar
  113. Wabitsch, M., Blum, W. F., Muche, R., Braun, M., Hube, F., Rascher, W., Heinze, E., Teller, W., and Hauner, H., (1997). Contribution of androgens to the gender difference in leptin production in obese children and adolescents. J. Clin. Invest., 100, 808–813.PubMedCrossRefGoogle Scholar
  114. Wabitsch, M., Ballauff, A., Holl, R., Blum, W. F., Heinze, E., Remschidt, H., and Hebebrand, J. (2001). Serum leptin, gonadotropin, and testosterone concentrations in male patients with anorexia nervosa during weight gain. J. Clin. Endocrinol. Metab., 86, 2982–2988.PubMedCrossRefGoogle Scholar
  115. Wang, J., Liu, R., Hawkins, M., Barzilai, N., and Rossetti, L. (1998). A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature, 393, 684–688.PubMedCrossRefGoogle Scholar
  116. Weimann, E., Blum, W. F., Witzel, C., Schwidergall, S., and Bohles, H. J. (1999). Hypoleptinemia in female and male elite gymnasts. Eur. J. Clin. Invest., 29, 853–860.PubMedCrossRefGoogle Scholar
  117. Yu, W. H., Kimura, M., Walczewska, A., Karanth, S., and McCann, S. M. (1997a). Role of leptin in hypothalamicpituitary function. Proc. Natl. Acad. Sci. USA, 94, 1023–1028.PubMedCrossRefGoogle Scholar
  118. Yu, W. H., Walczewska, A., Karanth, S., and McCann, S. M. (1997b). Nitric oxide mediates leptin-induced luteinizing hormone-releasing hormone (LHRH) and LHRH and leptin-induced LH release from the pituitary gland. Endocrinology, 138, 5055–5058.PubMedCrossRefGoogle Scholar
  119. Zhang, Y., Proenca, M., Maffei, M., Barone, M., Leopold, L., and Friedman, J. M. (1994). Positional cloning of the obese gene and its human homologue. Nature, 372, 425–432.PubMedCrossRefGoogle Scholar
  120. Zhang, Y., Basinski, M. B., Beals, J. M., Briggs, S. L., Churgay, L. M., Clawson, D. K., Di Marchi, R. D., Furman, T. C., Hale, J. E., Hsiung, H. M., Schoner, B. E., Smith, D. P., Zhang, X. Y., Wery, J. P., and Schevitz, R. W. (1997). Crystal structure of the obese protein leptin E-100. Nature, 387, 206–209.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Susann Blüher
    • 1
  • Christos S. Mantzoros
    • 1
  1. 1.Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical CenterHarvard Medical SchoolUSA

Personalised recommendations