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Erschienen in: Gynäkologische Endokrinologie 1/2006

01.02.2006 | Leitthema

Leptin

Neuroendokrine Wirkungen und Einflüsse auf den menstruellen Zyklus

verfasst von: Dr. S. Hahn, S. Tan, O. E. Janssen

Erschienen in: Gynäkologische Endokrinologie | Ausgabe 1/2006

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Zusammenfassung

Leptin, das als zentrales hungerregulierendes Stoffwechselhormon des Fettgewebes im Jahre 1994 entdeckt wurde, besitzt neben seinem Einfluss auf den Energiestoffwechsel auch eine Reihe weiterer endokriner Funktionen auf hypothalamisch-hypophysärer und gonadaler Ebene. Der Leptinsignalübertragungsweg ist sehr komplex und bisher nicht vollständig erforscht. Abweichungen vom normalen Körpergewicht beeinflussen den Leptinmetabolismus. Adipositas geht mit einer eingeschränkten Sensitivität für endogenes Leptin, der Leptinresistenz, einher, die kompensatorisch zu hohen Leptinspiegeln führt. Bei Unterernährung findet sich in Korrelation mit den dabei erniedrigten Leptinspiegeln eine Störung des Menstruationszyklus im Sinne einer Amenorrhö. Im Tiermodell konnte eine Assoziation zwischen Leptindefizienz und Infertilität gezeigt werden. Somit könnte Leptin ein Vermittler zwischen Fettgewebe und reproduktiver Funktion sein. Zusätzlich zu diesen Effekten besteht ein Zusammenhang zwischen Leptin und der Pubertätsentwicklung sowie schwangerschaftsspezifischen Problemen, wie beispielsweise einer fetalen Wachstumsretardierung. Wenngleich eine Vielzahl von Studien die Bedeutung des Leptins im Rahmen der Reproduktion dokumentiert, sind seine Funktion und Regulation noch nicht im Detail geklärt, und seine laborchemische Bestimmung besitzt im klinischen Alltag noch keine praktische Bedeutung.
Literatur
1.
Zurück zum Zitat Anifandis G, Koutselini E, Louridas K et al. (2005) Estradiol and leptin as conditional prognostic IVF markers. Reproduction 129:531–534CrossRefPubMed Anifandis G, Koutselini E, Louridas K et al. (2005) Estradiol and leptin as conditional prognostic IVF markers. Reproduction 129:531–534CrossRefPubMed
2.
Zurück zum Zitat Asimakopoulos B, Nikolettos N, Papachristou DN et al. (2005) Follicular fluid levels of vascular endothelial growth factor and leptin are associated with pregnancy outcome of normal women participating in intracytoplasmic sperm injection cycles. Physiol Res 54:263–270PubMed Asimakopoulos B, Nikolettos N, Papachristou DN et al. (2005) Follicular fluid levels of vascular endothelial growth factor and leptin are associated with pregnancy outcome of normal women participating in intracytoplasmic sperm injection cycles. Physiol Res 54:263–270PubMed
3.
Zurück zum Zitat Barash IA, Cheung CC, Weigle DS et al. (1996) Leptin is a metabolic signal to the reproductive system. Endocrinology 137:3144–3147CrossRefPubMed Barash IA, Cheung CC, Weigle DS et al. (1996) Leptin is a metabolic signal to the reproductive system. Endocrinology 137:3144–3147CrossRefPubMed
4.
Zurück zum Zitat Butte NF, Hopkinson JM, Nicolson MA (1997) Leptin in human reproduction: serum leptin levels in pregnant and lactating women. J Clin Endocrinol Metab 82:585–589CrossRefPubMed Butte NF, Hopkinson JM, Nicolson MA (1997) Leptin in human reproduction: serum leptin levels in pregnant and lactating women. J Clin Endocrinol Metab 82:585–589CrossRefPubMed
5.
Zurück zum Zitat Carmina E, Ferin M, Gonzalez F et al. (1999) Evidence that insulin and androgens may participate in the regulation of serum leptin levels in women. Fertil Steril 72:926–931CrossRefPubMed Carmina E, Ferin M, Gonzalez F et al. (1999) Evidence that insulin and androgens may participate in the regulation of serum leptin levels in women. Fertil Steril 72:926–931CrossRefPubMed
6.
Zurück zum Zitat Cella F, Giordano G, Cordera R (2000) Serum leptin concentrations during the menstrual cycle in normal-weight women: effects of an oral triphasic estrogen-progestin medication. Eur J Endocrinol 142:174–178CrossRefPubMed Cella F, Giordano G, Cordera R (2000) Serum leptin concentrations during the menstrual cycle in normal-weight women: effects of an oral triphasic estrogen-progestin medication. Eur J Endocrinol 142:174–178CrossRefPubMed
7.
Zurück zum Zitat Cioffi JA, Shafer AW, Zupancic TJ et al. (1996) Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat Med 2:585–589CrossRefPubMed Cioffi JA, Shafer AW, Zupancic TJ et al. (1996) Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat Med 2:585–589CrossRefPubMed
8.
Zurück zum Zitat Farooqi IS, Jebb SA, Langmack G et al. (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341:879–884CrossRefPubMed Farooqi IS, Jebb SA, Langmack G et al. (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341:879–884CrossRefPubMed
9.
Zurück zum Zitat Foster DL, Olster DH (1985) Effect of restricted nutrition on puberty in the lamb: patterns of tonic luteinizing hormone (LH) secretion and competency of the LH surge system. Endocrinology 116:375–381PubMed Foster DL, Olster DH (1985) Effect of restricted nutrition on puberty in the lamb: patterns of tonic luteinizing hormone (LH) secretion and competency of the LH surge system. Endocrinology 116:375–381PubMed
10.
Zurück zum Zitat Georgios A, Eleni K, Ioannis S et al. (2005) Serum and follicular fluid leptin levels are correlated with human embryo quality. Reproduction 130:917–921CrossRefPubMed Georgios A, Eleni K, Ioannis S et al. (2005) Serum and follicular fluid leptin levels are correlated with human embryo quality. Reproduction 130:917–921CrossRefPubMed
11.
Zurück zum Zitat Grinspoon SK, Askari H, Landt ML et al. (1997) Effects of fasting and glucose infusion on basal and overnight leptin concentrations in normal-weight women. Am J Clin Nutr 66:1352–1356PubMed Grinspoon SK, Askari H, Landt ML et al. (1997) Effects of fasting and glucose infusion on basal and overnight leptin concentrations in normal-weight women. Am J Clin Nutr 66:1352–1356PubMed
12.
Zurück zum Zitat Halaas JL, Gajiwala KS, Maffei M et al. (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543–546PubMed Halaas JL, Gajiwala KS, Maffei M et al. (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543–546PubMed
13.
Zurück zum Zitat Henry BA, Goding JW, Tilbrook AJ et al. (2001) Intracerebroventricular infusion of leptin elevates the secretion of luteinising hormone without affecting food intake in long-term food-restricted sheep, but increases growth hormone irrespective of bodyweight. J Endocrinol 168:67–77CrossRefPubMed Henry BA, Goding JW, Tilbrook AJ et al. (2001) Intracerebroventricular infusion of leptin elevates the secretion of luteinising hormone without affecting food intake in long-term food-restricted sheep, but increases growth hormone irrespective of bodyweight. J Endocrinol 168:67–77CrossRefPubMed
14.
Zurück zum Zitat Henson MC, Castracane VD (2005) Leptin in pregnancy: an update. Biol Reprod (in press) Henson MC, Castracane VD (2005) Leptin in pregnancy: an update. Biol Reprod (in press)
15.
Zurück zum Zitat Jockenhovel F, Blum WF, Vogel E et al. (1997) Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men. J Clin Endocrinol Metab 82:2510–2513CrossRefPubMed Jockenhovel F, Blum WF, Vogel E et al. (1997) Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men. J Clin Endocrinol Metab 82:2510–2513CrossRefPubMed
16.
Zurück zum Zitat Kendall NR, Gutierrez CG, Scaramuzzi RJ et al. (2004) Direct in vivo effects of leptin on ovarian steroidogenesis in sheep. Reproduction 128:757–765CrossRefPubMed Kendall NR, Gutierrez CG, Scaramuzzi RJ et al. (2004) Direct in vivo effects of leptin on ovarian steroidogenesis in sheep. Reproduction 128:757–765CrossRefPubMed
17.
Zurück zum Zitat King JC, Butte NF, Bronstein MN et al. (1994) Energy metabolism during pregnancy: influence of maternal energy status. Am J Clin Nutr 59:439S–445SPubMed King JC, Butte NF, Bronstein MN et al. (1994) Energy metabolism during pregnancy: influence of maternal energy status. Am J Clin Nutr 59:439S–445SPubMed
18.
Zurück zum Zitat Lado-Abeal J, Lukyanenko YO, Swamy S et al. (1999) Short-term leptin infusion does not affect circulating levels of LH, testosterone or cortisol in food-restricted pubertal male rhesus macaques. Clin Endocrinol (Oxf) 51:41–51CrossRef Lado-Abeal J, Lukyanenko YO, Swamy S et al. (1999) Short-term leptin infusion does not affect circulating levels of LH, testosterone or cortisol in food-restricted pubertal male rhesus macaques. Clin Endocrinol (Oxf) 51:41–51CrossRef
19.
Zurück zum Zitat Lee GH, Proenca R, Montez JM et al. (1996) Abnormal splicing of the leptin receptor in diabetic mice. Nature 379:632–635CrossRefPubMed Lee GH, Proenca R, Montez JM et al. (1996) Abnormal splicing of the leptin receptor in diabetic mice. Nature 379:632–635CrossRefPubMed
20.
Zurück zum Zitat Maffei M, Volpe L, Di Cianni G et al. (1998) Plasma leptin levels in newborns from normal and diabetic mothers. Horm Metab Res 30:575–580PubMed Maffei M, Volpe L, Di Cianni G et al. (1998) Plasma leptin levels in newborns from normal and diabetic mothers. Horm Metab Res 30:575–580PubMed
21.
Zurück zum Zitat Mantzoros CS, Dunaif A, Flier JS (1997) Leptin concentrations in the polycystic ovary syndrome. J Clin Endocrinol Metab 82:1687–1691CrossRefPubMed Mantzoros CS, Dunaif A, Flier JS (1997) Leptin concentrations in the polycystic ovary syndrome. J Clin Endocrinol Metab 82:1687–1691CrossRefPubMed
22.
Zurück zum Zitat Mantzoros CS, Flier JS, Rogol AD (1997) 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 Metab 82:1066–1070CrossRefPubMed Mantzoros CS, Flier JS, Rogol AD (1997) 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 Metab 82:1066–1070CrossRefPubMed
23.
Zurück zum Zitat Miller KK, Grinspoon S, Gleysteen S et al. (2004) Preservation of neuroendocrine control of reproductive function despite severe undernutrition. J Clin Endocrinol Metab 89:4434–4438CrossRefPubMed Miller KK, Grinspoon S, Gleysteen S et al. (2004) Preservation of neuroendocrine control of reproductive function despite severe undernutrition. J Clin Endocrinol Metab 89:4434–4438CrossRefPubMed
24.
Zurück zum Zitat Miller KK, Parulekar MS, Schoenfeld E et al. (1998) Decreased leptin levels in normal weight women with hypothalamic amenorrhea: the effects of body composition and nutritional intake. J Clin Endocrinol Metab 83:2309–2312CrossRefPubMed Miller KK, Parulekar MS, Schoenfeld E et al. (1998) Decreased leptin levels in normal weight women with hypothalamic amenorrhea: the effects of body composition and nutritional intake. J Clin Endocrinol Metab 83:2309–2312CrossRefPubMed
25.
Zurück zum Zitat Misra M, Miller KK, Almazan C et al. (2004) Hormonal and body composition predictors of soluble leptin receptor, leptin, and free leptin index in adolescent girls with anorexia nervosa and controls and relation to insulin sensitivity. J Clin Endocrinol Metab 89:3486–3495CrossRefPubMed Misra M, Miller KK, Almazan C et al. (2004) Hormonal and body composition predictors of soluble leptin receptor, leptin, and free leptin index in adolescent girls with anorexia nervosa and controls and relation to insulin sensitivity. J Clin Endocrinol Metab 89:3486–3495CrossRefPubMed
26.
Zurück zum Zitat Ostlund RE Jr, Yang JW, Klein S et al. (1996) Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab 81:3909–3913CrossRefPubMed Ostlund RE Jr, Yang JW, Klein S et al. (1996) Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab 81:3909–3913CrossRefPubMed
27.
Zurück zum Zitat Persson B, Westgren M, Celsi G et al. (1999) Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers. Horm Metab Res 31:467–471PubMed Persson B, Westgren M, Celsi G et al. (1999) Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers. Horm Metab Res 31:467–471PubMed
28.
Zurück zum Zitat Riad-Gabriel MG, Jinagouda SD, Sharma A et al. (1998) Changes in plasma leptin during the menstrual cycle. Eur J Endocrinol 139:528–531CrossRefPubMed Riad-Gabriel MG, Jinagouda SD, Sharma A et al. (1998) Changes in plasma leptin during the menstrual cycle. Eur J Endocrinol 139:528–531CrossRefPubMed
29.
Zurück zum Zitat Rosenbaum M, Nicolson M, Hirsch J et al. (1996) Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab 81:3424–3427CrossRefPubMed Rosenbaum M, Nicolson M, Hirsch J et al. (1996) Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab 81:3424–3427CrossRefPubMed
30.
Zurück zum Zitat Saad MF, Khan A, Sharma A et al. (1998) Physiological insulinemia acutely modulates plasma leptin. Diabetes 47:544–549PubMed Saad MF, Khan A, Sharma A et al. (1998) Physiological insulinemia acutely modulates plasma leptin. Diabetes 47:544–549PubMed
31.
Zurück zum Zitat Schwartz MW, Baskin DG, Bukowski TR et al. (1996) Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes 45:531–535PubMed Schwartz MW, Baskin DG, Bukowski TR et al. (1996) Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes 45:531–535PubMed
32.
Zurück zum Zitat Shibasaki T, Oda T, Imaki T et al. (1993) Injection of anti-neuropeptide Y gamma-globulin into the hypothalamic paraventricular nucleus decreases food intake in rats. Brain Res 601:313–316CrossRefPubMed Shibasaki T, Oda T, Imaki T et al. (1993) Injection of anti-neuropeptide Y gamma-globulin into the hypothalamic paraventricular nucleus decreases food intake in rats. Brain Res 601:313–316CrossRefPubMed
33.
Zurück zum Zitat Sinha MK, Opentanova I, Ohannesian JP et al. (1996) Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest 98:1277–1282PubMed Sinha MK, Opentanova I, Ohannesian JP et al. (1996) Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest 98:1277–1282PubMed
34.
Zurück zum Zitat Sivan E, Whittaker PG, Sinha D et al. (1998) Leptin in human pregnancy: the relationship with gestational hormones. Am J Obstet Gynecol 179:1128–1132CrossRefPubMed Sivan E, Whittaker PG, Sinha D et al. (1998) Leptin in human pregnancy: the relationship with gestational hormones. Am J Obstet Gynecol 179:1128–1132CrossRefPubMed
35.
Zurück zum Zitat Stanley BG, Anderson KC, Grayson MH et al. (1989) Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats. Physiol Behav 46:173–177CrossRefPubMed Stanley BG, Anderson KC, Grayson MH et al. (1989) Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats. Physiol Behav 46:173–177CrossRefPubMed
36.
Zurück zum Zitat Stock SM, Bremme KA (1998) Elevation of plasma leptin levels during pregnancy in normal and diabetic women. Metabolism 47:840–843CrossRefPubMed Stock SM, Bremme KA (1998) Elevation of plasma leptin levels during pregnancy in normal and diabetic women. Metabolism 47:840–843CrossRefPubMed
37.
Zurück zum Zitat Strobel A, Issad T, Camoin L et al. (1998) A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 18:213–215CrossRefPubMed Strobel A, Issad T, Camoin L et al. (1998) A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 18:213–215CrossRefPubMed
38.
Zurück zum Zitat Strowitzki T, Kellerer M, Capp E et al. (1998) Increase in serum leptin concentrations in women undergoing controlled ovarian hyperstimulation for assisted reproduction. Gynecol Endocrinol 12:167–169PubMed Strowitzki T, Kellerer M, Capp E et al. (1998) Increase in serum leptin concentrations in women undergoing controlled ovarian hyperstimulation for assisted reproduction. Gynecol Endocrinol 12:167–169PubMed
39.
Zurück zum Zitat Tartaglia LA, Dembski M, Weng X et al. (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263–1271CrossRefPubMed Tartaglia LA, Dembski M, Weng X et al. (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263–1271CrossRefPubMed
40.
Zurück zum Zitat Teirmaa T, Luukkaa V, Rouru J et al. (1998) Correlation between circulating leptin and luteinizing hormone during the menstrual cycle in normal-weight women. Eur J Endocrinol 139:190–194CrossRefPubMed Teirmaa T, Luukkaa V, Rouru J et al. (1998) Correlation between circulating leptin and luteinizing hormone during the menstrual cycle in normal-weight women. Eur J Endocrinol 139:190–194CrossRefPubMed
41.
Zurück zum Zitat Thong FS, McLean C, Graham TE (2000) Plasma leptin in female athletes: relationship with body fat, reproductive, nutritional, and endocrine factors. J Appl Physiol 88:2037–2044PubMed Thong FS, McLean C, Graham TE (2000) Plasma leptin in female athletes: relationship with body fat, reproductive, nutritional, and endocrine factors. J Appl Physiol 88:2037–2044PubMed
42.
Zurück zum Zitat Tuominen JA, Ebeling P, Stenman UH et al. (1997) Leptin synthesis is resistant to acute effects of insulin in insulin-dependent diabetes mellitus patients. J Clin Endocrinol Metab 82:381–382CrossRefPubMed Tuominen JA, Ebeling P, Stenman UH et al. (1997) Leptin synthesis is resistant to acute effects of insulin in insulin-dependent diabetes mellitus patients. J Clin Endocrinol Metab 82:381–382CrossRefPubMed
43.
Zurück zum Zitat Vettor R, De Pergola G, Pagano C et al. (1997) Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity. Eur J Clin Invest 27:1016–1024CrossRefPubMed Vettor R, De Pergola G, Pagano C et al. (1997) Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity. Eur J Clin Invest 27:1016–1024CrossRefPubMed
44.
Zurück zum Zitat Wabitsch M, Ballauff A, Holl R et al. (2001) Serum leptin, gonadotropin, and testosterone concentrations in male patients with anorexia nervosa during weight gain. J Clin Endocrinol Metab 86:2982–2988CrossRefPubMed Wabitsch M, Ballauff A, Holl R et al. (2001) Serum leptin, gonadotropin, and testosterone concentrations in male patients with anorexia nervosa during weight gain. J Clin Endocrinol Metab 86:2982–2988CrossRefPubMed
45.
Zurück zum Zitat Welt CK, Chan JL, Bullen J et al. (2004) Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 351:987–997CrossRefPubMed Welt CK, Chan JL, Bullen J et al. (2004) Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 351:987–997CrossRefPubMed
46.
Zurück zum Zitat Yu WH, Kimura M, Walczewska A et al. (1997) Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci USA 94:1023–1028CrossRefPubMed Yu WH, Kimura M, Walczewska A et al. (1997) Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci USA 94:1023–1028CrossRefPubMed
47.
Zurück zum Zitat Zachow RJ, Magoffin DA (1997) Direct intraovarian effects of leptin: impairment of the synergistic action of insulin-like growth factor-I on follicle-stimulating hormone-dependent estradiol-17 beta production by rat ovarian granulosa cells. Endocrinology 138:847–850CrossRefPubMed Zachow RJ, Magoffin DA (1997) Direct intraovarian effects of leptin: impairment of the synergistic action of insulin-like growth factor-I on follicle-stimulating hormone-dependent estradiol-17 beta production by rat ovarian granulosa cells. Endocrinology 138:847–850CrossRefPubMed
48.
Zurück zum Zitat Zhang Y, Proenca R, Maffei M et al. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432CrossRefPubMed Zhang Y, Proenca R, Maffei M et al. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432CrossRefPubMed
Metadaten
Titel
Leptin
Neuroendokrine Wirkungen und Einflüsse auf den menstruellen Zyklus
verfasst von
Dr. S. Hahn
S. Tan
O. E. Janssen
Publikationsdatum
01.02.2006
Verlag
Springer-Verlag
Erschienen in
Gynäkologische Endokrinologie / Ausgabe 1/2006
Print ISSN: 1610-2894
Elektronische ISSN: 1610-2908
DOI
https://doi.org/10.1007/s10304-005-0135-4

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