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Semin Reprod Med 2002; 20(2): 089-092
DOI: 10.1055/s-2002-32499
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

When Did Leptin Become a Reproductive Hormone?

V. Daniel Castracane1 , Michael C. Henson2
  • 1Department of Obstetrics and Gynecology and the Women's Health Research Center of Amarillo, Texas Tech University Health Sciences Center, Amarillo, Texas
  • 2Departments of Obstetrics and Gynecology, Physiology, and Structural and Cellular Biology, and the Tulane National Primate Research Center, Tulane University Health Sciences Center, New Orleans, Louisiana
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Publikationsverlauf

Publikationsdatum:
27. Juni 2002 (online)

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ABSTRACT

Almost 50 years ago the obese mouse model was identified, and parabiosis studies were able to demonstrate that some humoral factor was involved in adiposity, so that the genetics and endocrine nature of this process have been apparent for many years. With the discovery of leptin just a few years ago, early studies validated the role of this protein product of the obese gene. Early studies in the obese mouse model (ob/ob mouse) demonstrated that the genetic basis was truly a deficiency in leptin. Coincidentally, the relationship to fertility was also associated with leptin. These early studies were also able to demonstrate a relationship to puberty and the time of pubertal development. Very quickly, the recognition that the placenta was a source of leptin and that leptin levels were elevated in pregnancy in a number of species also broadened our appreciation of the relationship to reproductive functions. These many rapidly elucidated relationships to leptin were reported soon after the identification and availability of leptin as a research reagent and have firmly put leptin into the area of reproductive physiology in addition to establishing roles in metabolism, satiety, and energy metabolism. Subsequent studies have expanded all of these situations. Species beyond the rodent model, including the human, have now introduced these physiologic studies into the clinical arena and the role of leptin in fertility, puberty, pregnancy, and genetics. In this issue, all of these topics are reviewed to bring the reader up to date with leptin and its role in reproductive function, many of which overlap with the control of obesity.

KEYWORDS

Leptin - puberty - pregnancy - fertility - gender

REFERENCES

  • 1 Zhang Z, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese gene and its human homologue.  Nature . 1994;  372 425-432
    CrossrefPubMedGoogle Scholar
  • 2 Ingalls A M, Dickie M M, Snell G D. Obese, a new mutation in the house mouse.  Obes Res . 1996;  4 101
    PubMedGoogle Scholar
  • 3 Coleman D L. Effects of parabiosis of obese with diabetes and normal mice.  Diabetologia . 1973;  9 294-298
    PubMedGoogle Scholar
  • 4 Pelleymounter M A, Cullen M J, Baker M B. Effects of the obese gene product on body weight regulation in ob/ob mice.  Science . 1995;  269 540-543
    CrossrefPubMedGoogle Scholar
  • 5 Heymsfield S B, Greenberg A S, Fujioka K. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial.  JAMA . 1999;  282 1568-1575
    CrossrefPubMedGoogle Scholar
  • 6 Farooqi I S, Jebb S A, Langmack G. Effects of recombinant leptin therapy in a child with congenital leptin deficiency.  N Engl J Med . 1999;  341 879-884
    CrossrefPubMedGoogle Scholar
  • 7 Chehab F F, Lim M E, 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
    CrossrefPubMedGoogle Scholar
  • 8 Tartaglia L A. The leptin receptor.  J Biol Chem . 1997;  272 6093-6096
    PubMedGoogle Scholar
  • 9 Finn P D, Cunningham M J, Pau K Y, Spies H G, Clifton D K, Steiner R A. The stimulatory effect of leptin on the neuroendocrine reproductive axis of the monkey.  Endocrinology . 1998;  139 4652-4662
    CrossrefPubMedGoogle Scholar
  • 10 Mantzoros C S, Cramer D W, Liberman R F, Barbieri R L. Predictive value of serum and follicular fluid leptin concentrations during assisted reproductive cycles in normal women and in women with the polycystic ovarian syndrome.  Hum Reprod . 2000;  15 539-544
    CrossrefPubMedGoogle Scholar
  • 11 Cioffi J A, Van Blerkom J, Antczak M, Shafer A, Wittmer S, Snodgrass H R. The expression of leptin and its receptors in pre-ovulatory human follicles.  Mol Hum Reprod . 1997;  3 467-472
    CrossrefPubMedGoogle Scholar
  • 12 Loffler S, Aust G, Kohler U, Spanel-Borowski K. Evidence of leptin expression in normal and polycystic human ovaries.  Mol Hum Reprod . 2001;  7 1143-1149
    CrossrefPubMedGoogle Scholar
  • 13 Butzow T L, Moilanen J M, Lehtovirta M. Serum and follicular fluid leptin during in vitro fertilization: relationship among leptin increase, body fat mass, and reduced ovarian response.  J Clin Endocrinol Metab . 1999;  84 3135-3139
    CrossrefPubMedGoogle Scholar
  • 14 Brannian J D, Schmidt S M, Kreger D O, Hansen K A. Baseline non-fasting serum leptin concentration to body mass index ratio is predictive of IVF outcomes.  Hum Reprod . 2001;  16 1819-1826
    CrossrefPubMedGoogle Scholar
  • 15 Brannian J D, Hansen K A. Leptin and ovarian folliculogenesis: implications for ovulation induction and ART outcomes.  Sem Reprod Med . 2002;  20 103-112
    PubMedGoogle Scholar
  • 16 Chehab F F, Mounzih K, Lu R, Lim N E. Early onset of reproductive function in normal female mice treated with leptin.  Science . 1997;  275 88-90
    CrossrefPubMedGoogle Scholar
  • 17 Ahima R S, Dushay J, Flier S N, Prabakaran D, Flier J S. Leptin accelerates the onset of puberty in normal female mice.  J Clin Invest . 1997;  99 391-395
    CrossrefPubMedGoogle Scholar
  • 18 Mantzoros C S, Flier J S, Rogol A D. 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 . 1997;  82 1066-1070
    CrossrefPubMedGoogle Scholar
  • 19 Clayton P E, Gill M S, Hall C M, Tillmann V, Whatmore A J, Price D A. Serum leptin through childhood and adolescence.  Clin Endocrinol (Oxf) . 1997;  46 727-733
    CrossrefPubMedGoogle Scholar
  • 20 Ahmed M L, Ong K KL, Morrell D J. Longitudinal study of leptin concentrations during puberty: sex differences and relationship to changes in body composition.  J Clin Endocrinol Metab . 1999;  84 899-905
    CrossrefPubMedGoogle Scholar
  • 21 Plant T M, Durrant A R. Circulating leptin does not appear to provide a signal for triggering the initiation of puberty in the male rhesus monkey (Macaca mulatta).  Endocrinology . 1997;  138 4505-4508
    CrossrefPubMedGoogle Scholar
  • 22 Urbanski H F, Pau K Y. A biphasic developmental pattern of circulating leptin in the male rhesus macaque (Macaca mulatta).  Endocrinology . 1998;  139 2284-2286
    CrossrefPubMedGoogle Scholar
  • 23 Mann D R, Akinbami M A, Gould K G, Castracane V D. 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 . 2000;  62 285-291
    PubMedGoogle Scholar
  • 24 Mann D R, Plant T M. Leptin and pubertal development.  Sem Reprod Med . 2002;  20 93-102
    PubMedGoogle Scholar
  • 25 Farooqi I S. Leptin and the onset of puberty: insights from rodent and human genetics.  Sem Reprod Med . 2002;  20 139-144
    PubMedGoogle Scholar
  • 26 Hassink S G, deLancey E, Sheslow D V. Placental leptin: an important new growth factor in intrauterine and neonatal development.  Pediatrics . 1997;  100 1-6
    CrossrefPubMedGoogle Scholar
  • 27 Henson M C, Swan K F, O'Neil J S. Expression of placental leptin and leptin receptor transcripts in early pregnancy and at term.  Obstet Gynecol . 1998;  92 1020-1028
    CrossrefPubMedGoogle Scholar
  • 28 Henson M C, Castracane V D, O'Neil J S. Serum leptin concentrations and expression of leptin transcripts in placental trophoblast with advancing baboon pregnancy.  J Clin Endocrinol Metab . 1999;  84 2543-2549
    CrossrefPubMedGoogle Scholar
  • 29 Henson M C, Castracane V D. Leptin in pregnancy.  Biol Reprod . 2000;  63 1219-1228
    PubMedGoogle Scholar
  • 30 Green A E, O'Neil J S, Swan K F, Bohm Jr P R, Ratterree M S, Henson M C. Leptin receptor transcripts are constitutively expressed in placenta and adipose tissue with advancing baboon pregnancy.  Proc Soc Exp Biol Med . 2000;  223 362-366
    CrossrefPubMedGoogle Scholar
  • 31 Castracane V D, Goldzieher J W. The relationship of estrogen to placental steroidogenesis in the baboon.  J Clin Endocrinol Metab . 1986;  62 1163-1166
    PubMedGoogle Scholar
  • 32 Castracane V D, Goldzieher J W. Timing of the luteal-placental shift in the baboon (Papio cynocephalus).  Endocrinology . 1986;  118 506-512
    PubMedGoogle Scholar
  • 33 Albrecht E D, Pepe G J. Endocrinology of pregnancy. In: Brans YW, Kuehl TJ, eds. Non-Human Primates in Perinatal Research New York: John Wiley and Sons 1988: 13-78
    Google Scholar
  • 34 Henson M C. Pregnancy maintenance and the regulation of placental progesterone biosynthesis in the baboon.  Hum Reprod Update . 1998;  4 389-405
    CrossrefPubMedGoogle Scholar
  • 35 Chardonnens D, Cameo P, Aubert M L. Modulation of human cytotrophoblastic leptin secretion by interleukin-1 alpha and 17 beta-oestradiol and its effect on HCG secretion.  Mol Hum Reprod . 1999;  5 1077-1082
    CrossrefPubMedGoogle Scholar
  • 36 Yura S, Sagawa N, Ogawa Y. Augmentation of leptin synthesis and secretion through activation of protein kinase A and C in cultured human trophoblastic cells.  J Clin Endocrinol Metab . 1998;  83 3609-3614
    CrossrefPubMedGoogle Scholar
  • 37 Henson M C, Castracane V D. Leptin: roles and regulation in primate pregnancy.  Sem Reprod Med . 2002;  20 113-122
    PubMedGoogle Scholar
  • 38 Poston L. Leptin and preeclampsia.  Sem Reprod Med . 2002;  20 131-138
    PubMedGoogle Scholar
  • 39 Christou H, Serdy S, Mantzoros C S. Fetal leptin in relation to growth and development processes in the fetus.  Sem Reprod Med . 2002;  20 123-130
    PubMedGoogle Scholar
  • 40 Shimizu H, Shimomura Y, Nakanishi Y. Estrogen increases in vivo leptin production in rats and human subjects.  J Endocrinol . 1997;  154 285-292
    CrossrefPubMedGoogle Scholar
  • 41 Behre H M, Simoni M, Nieschlag E. Strong association between serum levels of leptin and testosterone in men.  Clin Endocrinol (Oxf) . 1997;  47 237-240
    CrossrefPubMedGoogle Scholar
  • 42 Lado-Abeal J, Norman R L. Leptin and reproductive function in males.  Sem Reprod Med . 2002;  20 145-152
    PubMedGoogle Scholar
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