From Venus of Willendorf to leptin – history
of discovery of that cytokine and its relation with
human male reproductive system
Article published in Urologia Polska 2008/61/4.
Witold Malendowicz, Zbigniew Kwias
- Katedra i Klinika Urologii i Onkologii Urologicznej Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
prostate obesity leptin
- From the beginning of the human species, obesity was accompanied by us. Obesity fascinated all people generations, obese persons
- were illustrated in the art, and frequently reported as a medical cases. At the end of XX century progress in biomedicine allowed to
- recognize numerous factors involved in control of energy homeostasis. Earlier two recessive mutations ob/ob and db/db associated
- with massive obesity, were discovered in years 1950-1960. Subsequent experiments with parabiotic mice demonstrated the presence
- of blood – borne factor(s) involved in control of obesity. In 1994 that factor was identified and named leptin (from Greek leptos).
- Secreted primarily by the white adipose tissue, this peptide hormone appeared to be a molecule linking body fat mass with the hypothalamus.
- The primary function of leptin is to decrease caloric intake and increase energy expenditure. Moreover, leptin is involved in
- regulating numerous biological systems and organs. This review presents the most important facts on leptin action within the human
- male reproductive system.
- Ingalls AM, Dickie MM, Snell GD: Obese, a new mutation in the house mouse. J Hered 1950, 41, 317-318.
- Coleman DL, Hummel KP: Effects of parabiosis of normal with genetically diabetic mice. Am J Physiol 1969, 217, 1298-1304.
- Kennedy GC: The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci 1953, 140, 578-592.
- Minh L: Leptin: a piece of the obesity pie. The Science Creative Quarterly: http://www.scq.ubc.ca/leptin-a-piece-of-the-obesity-pie/
- Zhang Y, Proenca R, Maffei M et al: Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372, 425-432.
- Zhang F, Basinski MB, Beals JM et al: Crystal structure of the obese protein leptin-E100. Nature 1997, 387, 206-209.
- Auwerx J, Steals B: Leptin. Lancet 1998, 351, 737-742.
- Sagawa N, Yura S, Mise H et al: Role of Leptin in Pregnancy - A Rewiew Placenta, Trophoblast Resarch, 23 (Suppl A), 2002, 16, S80-S86.
- Considine RV, Sinah MK, Heiman ML et al: Serum immunoreactive - leptin concentrations in normal - weight and obese humans. N Engl J Med 1996, 334, 324-325.
- Silha JV, Krsek M, Skrha JV et al: Plasma resistin, adiponectin and leptin levels in lean and obese subjects: corelations with insulin resistance. Eur J Endocrinol 2003, 149, 331-335.
- Klein S, Coppack SW, MohamedAli V, Landt M: Adipose tissue leptin production, and plasma leptin kinetics in human. Diabetes 1996, 45, 984-987.
- Hill RA, Margetic S, Pegg GG, Gazzola C: Leptin: its pharmacokinetics and tissue distribution. Int J Obes Relat Metab Disord 1998, 22, 765-770.
- Tartaglia LA, Dembski M, Weng X et al: Identification and expression of leptin receptor OB-R. Cell 1995, 83, 1263-1271.
- Markowska A: Rola leptyny w patofizjologii macicy. Wydawnictwo Naukowe UAM, Poznań, 2006.
- Tartaglia LA: The leptin receptor. J Biol Chem 1997, 272, 6093-6106.
- Ahima RS, Saper CB, Flier JS, Elmquist JK: Leptin regulation of neuroendocrine system. Front Neuroendocrinol 2000, 21, 263-307.
- Fei H, Okano HJ, Li C et al: Anatomic localization of alternatively spliced leptin receptors (OB. R) in mouse brain, and other tissues. Proc Natl Acad Sci USA 1997, 94, 7001-7005.
- Elmquist JK, Bjorbaek C, Ahima RS et al: Distributions of leptin receptor mRNA isoforms in the rat brain. J Comp Neurol 1998, 395, 535-547.
- Mercer JG, Hoggard N, Williams LM et al: Localization of leptin receptor mRNA, and the long form splice variant (Ob Rb) in mouse hypothalamus, and adjacent brain regions by in situ hybridization. FEBS Lett 1996, 387, 113-116.
- Guan XM, Hess JF, Yu H et al: Differential expression of mRNA for leptin receptor isoforms in the rat brain. Mol Cell Endocrinol 1997, 133, 1-7.
- Montague CT, Farooqi IS, Whitehead JP et al: Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997, 387, 903-908.
- Strobel A, Issad T, Camoin L et al: A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998, 18, 213-215.
- Clement K, Vaisse C, Lahlou N et al: A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998, 392, 398-401.
- Gueorguiev M, Goth ML, Korbonits M: Leptin and puberty: a review. Pituitary 2001, 4, 79-86.
- O’Rahilly S: Leptin: defining its role in humans by the clinical study of genetic disorders. Nutr Rev 2002, 60, S30-S4.
- Heymsfield SB, Fong TM, Gantz I, Erondu N: Fat and energy partitioning: longitudinal observations in leptin-treated adults homozygous for a Lep mutation. Obesity 2006, 14, 258-265.
- O’Rahilly S, Farooqi IS: The genetics of obesity in humans, w: Obesity Ed: Tschoep M Endotext.com 2006, 27, 710-718.
- Rau H, Reaves BJ, O’Rahilly S, Whitehead JP: Truncated human leptin (delta133) associated with extreme obesity under goes proteasomal degradation after defective intracellular transport. Endocrinology 1999, 140, 1718-1723.
- Erickson JC, Hollopeter G, Palmiter RD: Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 1996, 274, 1704-1707.
- Ewart-Toland A, Mounzih K, Qiu J, Chehab FF: Effect of the genetic background on the reproduction of leptin-deficient obese mice. Endocrinology 1999, 140, 732-738.
- Chehab FF, Lim ME, Lu R: Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 1996, 12, 318-320.
- Chan JL, Mantzoros CS: Leptin and the hypothalamic-pituitary regulation of the gonadotropin-gonadal axis. Pituitary 2001, 4, 87-92.
- Watanobe H, Schioth HB: Postnatal profile of plasma leptin concentrations in male and female rats: relation with the maturation of the pituitary-gonadal axis. Regul Pept 2002, 105, 23-28.
- Pinilla L, Seoane LM, Gonzalez L et al: Regulation of serum leptin levels by gonadal function in rats. Eur J Endocrinol 1999, 140, 468-473.
- Yu WH, Kimura M, Walczewska A et al: Role of leptin in hypothalamicpituitary function. Proc Natl Acad Sci USA 1997, 94, 1023-1028.
- Magni P, Vettor R, Pagano C et al: Expression of a leptin receptor in immortalized gonadotropin-releasing hormone-secreting neurons. Endocrinology 1999, 140, 1581-1585.
- Steiner J, LaPaglia N, Kirsteins L et al: The response of the hypothalamicpituitary- gonadal axis to fasting is modulated by leptin. Endocr Res 2003, 29, 107-117.
- Iqbal J, Pompolo S, Considine RV, Clarke IJ: Localization of leptin receptor-like immunoreactivity in the corticotropes, somatotropes, and gonadotropes in the ovine anterior pituitary. Endocrinology 2000, 141,1515-1520.
- Korbonits M, Chitnis MM, Gueorguiev M et al: Leptin in pituitary adenomas - a novel paracrine regulatory system. Pituitary 2001, 4, 49-55.
- Korbonits M, Chitnis MM, Gueorguiev M et al: The release of leptin and its effect on hormone release from human pituitary adenomas. ClinEndocrinol (Oxf) 2001, 54, 781-789.
- Kristiansen MT, Clausen LR, Nielsen S et al: Expression of leptin receptor isoforms and effects of leptin on the proliferation and hormonal secretion in human pituitary adenomas. Horm Res 2004, 62, 129-136.
- Caprio M, Fabbrini E, Isidori AM et al: Leptin in reproduction. Trends Endocrinol Metab 2001, 12, 65-72.
- Spicer LJ, Francisco CC: The adipose obese gene product, leptin: evidence of a direct inhibitory role in ovarian function. Endocrinology 1997, 138, 3374-3379.
- Spicer LJ, Francisco CC: Adipose obese gene product, leptin, inhibits bovine ovarian thecal cell steroidogenesis. Biol Reprod 1998, 58, 207-212.
- Tena-Sempere M, Barreiro ML: Leptin in male reproduction: the testis paradigm. Mol Cell Endocrinol 2002, 188, 9-13.
- Garcia-Mayor RV, Andrade MA, Rios M et al: Serum leptin levels in normal children: Relationship to age, gender, body mass index, pituitary - gonadal hormones and pubertal stage. J Clin Endocrinol Metab 1997, 82, 2849-2855.
- Farooqi IS, Jebb SA, Langmack G et al: Effects of recombinat leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999, 341, 879-884.
- Ozata M, Ozdemir IC, Licinio J: Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decrased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin - mediated defects. J Clin Endocrinol Metab 1999, 84, 3686-3695.
- Bergstrom A, Pisani P, Tenet V et al: Overweight as an avoidable cause of cancer in Europe. Int J Cancer 2001, 91, 421-430.
- Bray GA: The underlying basis for obesity: relationship to cancer. J Nutr 2002, 132, 3451S-3455S.
- Freedland SJ, Aronson WJ: Examining the relationship between obesity and prostate cancer. Rev Urol 2004, 6, 73-81.
- Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003, 348, 1625-1638.
- Cioffi JA, Shafer AW, Zupancic TJ et al: Novel B219/OB. Receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat Med 1996, 2, 585-589.
- Stattini P, Soderberg S, Hallmans G et al: Leptin is associated with increased prostate cancer risk: a nested case - referent study. J Ciln Endocrinol Metab 2001, 86, 1341-1345.
- Malendowicz W, Ruciński M, Macchi C et al: Leptin and leptin receptors in the prostate and seminal vesicles of the adult rat. Int J Mol Med 2006, 18, 615-619.
- Somasundar P, Yu A, Vona-Davis L, McFadden DW: Differential responses of leptin on cancer in vitro. J Surg Res 2002, 113, 50.
- Onuma M, Bub JD, Rummel TL, Iwamoto Y: Prostate cancer cell - adipocyte interaction: leptin mediates androgen - independent prostate cell
- proliferation through c - Jun NH2 - terminal kinase. J Biol Chem 2003, 278, 42660-42667.
- Frankenberry KA, Somasundar P, McFadden DW, Vona-Davis LC: Leptin induces cell migration and the expression of growth factors in humanprostate cancer cells. Am J Surg 2004, 188, 560-565.
- Malendowicz W, Ruciński M, Belloni AS et al: Real-time PCR analysis of leptin and leptin receptor expression in the rat prostate, and effects of leptin on prostatic acid phosphatase release. Int J Mol Med 2006, 18, 1097-1101.
- Nazian SJ, Cameron DF: Temporal relation between leptin and various indices of sexual maturation in the male rat. J Androl 1999, 20, 487-491.
- Lagiou P, Signorello LB, Trichopoulos D et al: Leptin in relation to prostate cancer and benign prostatic hyperplasia. Int J Cancer 1998, 76, 25-28.
- Hsing AW, Chua S, Gao YT et al: Prostate cancer risk and serum levels of insulin and leptin: a population based study. J Nat Cancer Inst 2001, 93, 10, 783-789.
- Neugut AI, Chen AC, Petrylak DP: The “skinny” on obesity and prostate cancer prognosis. J Clin Oncol 2004, 22, 395-398.
- Baillargeon J, Platz EA, Rose DP et al: Obesity, adipokines, and prostate cancer in a prospective population-based study. Cancer Epidemiol Biomarkers Prev 2006, 15, 1331-1335.
- Stattini P, Kaaks R, Johansson R et al: Plasma leptin is not associated with prostate cancer risk. Cancer Epidemiol Biomarkers Prev 2003, 12, 474-475.
- Gade-Andavolu R, Cone LA, Shu S et al: Molecular interactions of leptin and prostate cancer. Cancer J 2006, 12, 201-206.
- Saglam K, Aydur E, Yilmaz M, Goktas S: Leptin influences cellular differentiation and progression in prostate cancer. J Urol 2003, 169, 1308-1311.
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