19
Views
2
CrossRef citations to date
0
Altmetric
Review

Role of leptin and ghrelin in the regulation of gonadal function

, , , &
Pages 239-249 | Published online: 10 Jan 2014

References

  • Fink G. Neuroendocrine regulation of pituitary function: general principles. In: a Neuroendocrinology in Physiology and Medicine. Conn PM, Freeman ME (Eds). Humana Press, NJ, USA, 107–134 (2000).
  • Tena-Sempere M, Huhtaniemi IT. Gonadotropins and gonadotropin receptors. In: Reproductive Medicine. Molecular, Cellular and Genetic Fundamentals. Fauser BCJM (Ed.). Parthenon Publishing, NY, USA, 225–244 (2003).
  • Barash IA, Cheung CC, Weigle DS et al. Leptin is a metabolic signal to the reproductive system. Endocrinology137(7), 3144–3147 (1996).
  • Casanueva FF, Dieguez C. Neuroendocrine regulation and actions of leptin. Front. Neuroendocrinol.20(4), 317–363 (1999).
  • Mystkowski P, Schwartz MW. Gonadal steroids and energy homeostasis in the leptin era. Nutrition16(10), 937–946 (2000).
  • Kennedy GC, Mitra J. Body weight and food intake as initiating factors for puberty in the rat. J. Physiol.166, 408–418 (1963).
  • Frisch R, Revelle R. Height and weight at menarche: a hypothesis of critical body weights and adolescent events. Science169(943), 397–399 (1970).
  • Frisch R, McArthur J. Menstrual cycles: fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science185(4155), 949–951 (1974).
  • Ahima RS, Saper CB, Flier JS, Elmquist JK. Leptin regulation of neuroendocrine systems. Front. Neuroendocrinol.21(3), 263–307 (2000).
  • Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature372(6505), 425–432 (1994).
  • Friedman JM, Halaas JL. Leptin and regulation of body weight in mammals. Nature395(6704), 763–770 (1998).
  • Sahu A. A hypothalamic role in energy balance with special emphasis on leptin. Endocrinology145(6), 2613–2620 (2004).
  • Rosenbaum M, Leibel RL. Leptin; a molecule integrating somatic energy stores, energy expenditure and fertility. Trends Endocrinol. Metab.9, 117–124 (1998).
  • Wauters M, Considine RV, van Gaal LF. Human leptin: from an adipocyte hormone to an endocrine mediator. Eur. J. Endocrinol.143(3), 293–311 (2000).
  • Chehab FF, Mounzih K, Lim ME. Early onset of reproductive function in normal female mice treated with leptin. Science275(5296), 88–90 (1997).
  • Cheung CC, Thornton JE, Nurani SD, Clifton DK, Steiner RA. A reassessment of leptin’s role in triggering the onset of puberty in the rat and mouse. Neuroendocrinology74(1), 12–21 (2001).
  • Carro E, Pinilla L, Seoane LM et al. Influence of endogenous leptin tone on the estrous cycle and luteinizing hormone pulsatility in female rats. Neuroendocrinology66(6), 375–377 (1997).
  • Nagatani S, Guthikonda P, Thompson RC, Tsukamura H, Maeda KI, Foster DL. Evidence for GnRH regulation by leptin: leptin administration prevents reduced pulsatile LH secretion during fasting. Neuroendocrinology67(6), 370–376 (1998).
  • Watanobe H. Leptin directly acts within the hypothalamus to stimulate gonadotropin-releasing hormone secretion in vivo in rats. J. Physiol.545(Pt 1), 255–268 (2002).
  • Magni P, Vettor R, Pagano C et al. Expression of a leptin receptor in immortalized gonadotropin-releasing hormone-secreting neurons. Endocrinology140(4), 1581–1585 (1999).
  • Smith JT, Acohido BV, Clifton DK, Steiner RA. KiSS-1 neurons are direct targets for leptin in the ob/ob mouse. J. Neuroendocrinol.18(4), 298–303 (2006).
  • Tena-Sempere M. GPR54 and kisspeptin in reproduction. Hum. Reprod. Update12(5), 631–639 (2006).
  • Castellano JM, Navarro VM, Fernandez-Fernandez R et al. Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology146(9), 3917–3925 (2005).
  • Zamorano PL, Mahesh VB, de Sevilla LM, Chorich LP, Bhat GK, Brann DW. Expression and localization of the leptin receptor in endocrine and neuroendocrine tissues of the rat. Neuroendocrinology65(3), 223–228 (1997).
  • Tena-Sempere M, Pinilla L, González LC, Dieguez C, Casanueva FF, Aguilar E. Leptin inhibits testosterone secretion from adult rat testis in vitro. J. Endocrinol.161(2), 211–218 (1999).
  • Tena-Sempere M, Pinilla L, González LC et al.In vitro pituitary and testicular effects of leptin-related synthetic peptide, leptin116–130 amide, involve actions both similar to and distinct from those of the native leptin molecule in the adult rat. Eur. J. Endocrinol.142(4), 406–410 (2000).
  • Caprio M, Isidori AM, Carta AR, Moretti C, Dufau ML, Fabbri A. Expression of functional leptin receptors in rodent Leydig cells. Endocrinology140(11), 4939–4947 (1999).
  • Giovambattista A, Suescun MO, Nessralla CC, Franca LR, Spinedi E, Calandra RS. Modulatory effects of leptin on Leydig cell function of normal and hyperleptinemic rats. Neuroendocrinology78(5), 270–279 (2003).
  • Tena-Sempere M, Manna PR, Zhang F-P et al. Molecular mechanisms of leptin action in adult rat testis: potential targets for leptin-induced inhibition of steroidogenesis and pattern of leptin receptor messenger ribonucleic acid expression. J. Endocrinol.170(2), 413–423 (2001).
  • Isidori AM, Caprio M, Strollo F et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J. Clin. Endocrinol. Metab.84(10), 3673–3680 (1999).
  • Caprio M, Fabbrini E, Isidori AM, Aversa A, Fabbri A. Leptin in reproduction. Trends Endocrinol. Metab.12(2), 65–72 (2001).
  • Tena-Sempere M, Pinilla L, Zhang F-P et al. Developmental and hormonal regulation of leptin receptor (Ob-R) messenger ribonucleic acid expression in rat testis. Biol. Reprod.64(2), 634–643 (2001).
  • Caprio M, Fabbrini E, Ricci G et al. Ontogenesis of leptin receptor in rat Leydig cells. Biol. Reprod.68(4), 1199–1207 (2003).
  • El-Hefnawy T, Ioffe S, Dym M. Expression of the leptin receptor during germ cell development in the mouse testis. Endocrinology141(7), 2624–2630 (2000).
  • Tartaglia LA. The leptin receptor. J. Biol. Chem.272(10), 6093–6096 (1997).
  • White DW, Tartaglia LA. Evidence for ligand-independent homo-oligomerization of leptin receptor (OB-R) isoforms: a proposed mechanism permitting productive long-form signalling in the presence of excess short-form expression. J. Cell Biochem.73, 278–288 (1999).
  • Mounzih K, Lu R, Chahab FF. Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology138(3), 1190–1193 (1997).
  • Bhat GK, Sea TL, Olantinwo MO et al. Influence of a leptin deficiency on testicular morphology, germ cell apoptosis, and expression levels of apoptosis-related genes in the mouse. J. Androl.27(2), 302–310 (2006).
  • Camina JP, Lage M, Menendez C et al. Evidence for free leptin in human seminal plasma. Endocrine17(3), 169–174 (2002).
  • Glander HJ, Lammert A, Paasch U, Glasow A, Kratzsch J. Leptin exits in tubuli seminiferi and in seminal plasma. Andrologia34(4), 227–233 (2002).
  • Zachow RJ, Magoffin DA. Direct intraovarian effects of leptin: impairment of the synergistic action of insulin-like growth factor-I on follicle-stimulating hormone-dependent estradiol-17-β production by rat ovarian granulosa cells. Endocrinology138(2), 847–850 (1997).
  • Spicer LJ, Francisco CC. The adipose obese gene product, leptin: evidence of a direct inhibitory role in ovarian function. Endocrinology138(8), 3374–3379 (1997).
  • Agarwal SK, Vogel K, Weitsman SR, Magoffin DA. Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulose and theca cells of the human ovary. J. Clin. Endocrinol. Metab.84(3), 1072–1076 (1999).
  • Ghizzoni L, Barreca A, Mastorakos G et al. Leptin inhibits steroid biosynthesis by human granulosa–lutein cells. Horm. Metab. Res.33(6), 323–328 (2001).
  • Kendall NR, Gutierrez CG, Scaramuzzi RJ, Baird DT, Webb R, Campbell BK. Direct in vivo effects of leptin on ovarian steroidogenesis in sheep. Reproduction128(6), 757–765 (2004).
  • Archanco M, Muruzabal FJ, Llopiz D et al. Leptin expression in the rat ovary depends on estrous cycle. J. Histochem. Cytochem.51(10), 1269–1277 (2003).
  • Kitawaki J, Kusuki I, Koshiba H, Tsukamoto K, Honjo H. Leptin directly stimulates aromatase activity in human luteinized granulosa cells. Mol. Hum. Reprod.5(8), 708–713 (1999).
  • Swain JE, Dunn RL, McConnell D, Gonzalez-Martinez J, Smith GD. Direct effects of leptin on mouse reproductive function: regulation of follicular, oocyte, and embryo development. Biol. Reprod.71(5), 1446–1452 (2004).
  • Karlsson C, Lindell K, Svensson E et al. Expression of functional leptin receptors in the human ovary. J. Clin. Endocrinol. Metab.82(12), 4144–4148 (1997).
  • Duggal PS, Weitsman SR, Magoffin DA, Norman RJ. Expression of the long (Ob-RB) and the short (Ob-RA) forms of leptin receptor throughout the estrous cycle in the mature rat ovary. Reproduction123(6), 899–905 (2002).
  • Abir R, Ao A, Jin S et al. Leptin and its receptors in human fetal and adult ovaries. Fertil. Steril.84(6), 1779–1782 (2005).
  • Loffler S, Aust G, Kohler U, Spanel-Borowski K. Evidence of leptin expression in normal and polycystic human ovaries. Mol. Hum. Reprod.7(12), 1143–1149 (2001).
  • Ryan NK, Woodhouse CM, van der Hoek KH, Gilchrist RB, Armstrong DT, Norman RJ. Expression of leptin and its receptor in the murine ovary: possible role in the regulation of oocyte maturation. Biol. Reprod.66(5), 1548–1554 (2002).
  • Ryan NK, van der Hoek KH, Robertson SA, Norman RJ. Leptin and leptin receptor expression in the rat ovary. Endocrinology144(11), 5006–5013 (2003).
  • Kikuchi N, Andoh K, Abe Y, Yamada K, Mizunuma H, Ibuki Y. Inhibitory action of leptin on early follicular growth differs in immature and adult female mice. Biol. Reprod.65(1), 66–71 (2001).
  • Duggal PS, van der Hoek KH, Milner CR et al. The in vivo and in vitro effects of exogenous leptin on ovulation in the rat. Endocrinology141(6), 1971–1976 (2000).
  • Craig J, Zhu H, Dyce PW, Petrik J, Li J. Leptin enhances oocyte nuclear and cytoplasmatic maturation via the mitogen-activated protein kinase pathway. Endocrinology145(11), 5355–5363 (2004).
  • Barkan D, Hurgin V, Dekel N, Amsterdam A, Rubinstein M. Leptin induces ovulation in GnRH-deficient mice. FASEB J.19(1), 133–135 (2005).
  • Olatinwo MO, Bhat GK, Stah CD, Mann DR. Impact of gonadotropin administration on folliculogenesis in prepubertal ob/ob mice. Mol. Cell. Endocrinol.245(1–2), 121–127 (2005).
  • Brannian JD, Hansen KA. Leptin and ovarian folliculogenesis: implications for ovulation induction and ART outcomes. Semin. Reprod. Med.20(2), 103–112 (2002).
  • Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of the polycystic ovary syndrome. Clin. Endocrinol.60(1), 1–17 (2004).
  • Cervero A, Dominguez F, Horcajadas JA, Quinonero A, Pellicer A, Simon C. The role of leptin in reproduction. Curr. Opin. Obstet. Gynecol.18(3), 297–303 (2006).
  • Lindheim SR, Sauer MV, Carmina E, Chang PL, Zimmerman R, Lobo RA. Circulating leptin levels during ovulation induction: relation to adiposity and ovarian morphology. Fertil. Steril.73(3), 493–498 (2000).
  • Luukkaa V, Pesonen U, Huhtaniemi I et al. Inverse correlation between serum testosterone and leptin in men. J. Clin. Endocrinol. Metab.83(9), 3243–3246 (1998).
  • Kojima M, Hosada H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone releasing acylated peptide from stomach. Nature402(6762), 656–660 (1999).
  • van der Lely AJ, Tschop M, Heiman ML, Ghigo E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr. Rev.25(3), 426–457 (2004).
  • Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB. Ghrelin – a hormone with multiple functions. Front. Neuroendocrinol.25(1), 27–68 (2004).
  • Gauna C, Delhanty PJ, van Aken MO et al. Unacylated ghrelin is active on the INS-1E rat insulinoma cell line independently of the growth hormone secretagogue receptor type 1a and the corticotropin releasing factor 2 receptor. Mol. Cell. Endocrinol.251, 103–111 (2006).
  • Toshinai K, Yamaguchi H, Sun Y et al. Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology147, 2306–2314 (2006).
  • Martini AC, Fernandez-Fernandez R, Tovar S et al. Comparative analysis of the effects of ghrelin and un-acylated ghrelin upon luteinizing hormone secretion in male rats. Endocrinology147, 2374–2382 (2006).
  • Zigman JM, Elmquist JK. From anorexia to obesity – the yin and yang of body weight control. Endocrinology144, 3749–3756 (2003).
  • Furuta M, Funabashi T, Kimura F. Intracerebroventricular administration of ghrelin rapidly suppresses pulsatile luteinizing hormone secretion in ovariectomized rats. Biochem. Biophys. Res. Commun.288, 780–785 (2001).
  • Vulliemoz NR, Xiao E, Xia-Zhang L, Germond M, Rivier J, Ferin M. Decrease in luteinizing hormone pulse frequency during a five-hour peripheral ghrelin infusion in the ovariectomized rhesus monkey. J. Clin. Endocrinol. Metab.89, 5718–5723 (2004).
  • Iqbal J, Kurose Y, Canny B, Clarke IJ. Effects of central infusion of ghrelin on food intake and plasma levels of growth hormone, luteinizing hormone, prolactin, and cortisol secretion in sheep. Endocrinology147, 510–519 (2006).
  • Fernandez-Fernandez R, Tena-Sempere M, Aguilar E, Pinilla L. Ghrelin effects on gonadotropin secretion in male and female rats. Neurosci. Lett.362, 103–107 (2004).
  • Fernandez-Fernandez R, Tena-Sempere M, Navarro VM et al. Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats: in vivo and in vitro studies. Neuroendocrinology82, 245–255 (2005).
  • Fernandez-Fernandez R, Navarro VM, Barreiro ML et al. Effects of chronic hyperghrelinemia on puberty onset and pregnancy outcome in the rat. Endocrinology146, 3018–3025 (2005).
  • Tena-Sempere M, Barreiro ML, Gonzalez LC et al. Novel expression and functional role of ghrelin in rat testis. Endocrinology143, 717–725 (2002).
  • Barreiro ML, Gaytan F, Caminos JE et al. Cellular location and hormonal regulation of ghrelin expression in rat testis. Biol. Reprod.67, 1768–1776 (2002).
  • Barreiro ML, Suominen JS, Gaytan F et al. Developmental, stage-specific and hormonally regulated expression of growth hormone secretagogue receptor messenger RNA in rat testis. Biol. Reprod.68, 1631–1640 (2003).
  • Gnanapavan S, Kola B, Bustin SA et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J. Clin. Endocrinol. Metab.87, 2988–2991 (2002).
  • Gaytan F, Barreiro ML, Caminos JE et al. Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors. J. Clin. Endocrinol. Metab.89, 400–409 (2004).
  • Papotti M, Ghe C, Cassoni P et al. Growth hormone secretagogue binding sites in peripheral human tissues. J. Clin. Endocrinol. Metab.85, 3803–3807 (2000).
  • Barreiro ML, Gaytan F, Castellano JM et al. Ghrelin inhibits the proliferative activity of immature Leydig cells in vivo and regulates stem cell factor messenger ribonucleic acid expression in rat testis. Endocrinology145, 4825–4834. (2004).
  • Hakovirta H, Yan W, Kaleva M et al. Function of stem cell factor as a survival factor of spermatogonia and localization of messenger ribonucleic acid in the rat seminiferous epithelium. Endocrinology140, 1492–1498 (1999).
  • Caminos JE, Tena-Sempere M, Gaytan F et al. Expression of ghrelin in the cyclic and pregnant rat ovary. Endocrinology144, 1594–1602 (2003).
  • Gaytan F, Barreiro ML, Chopin LK et al. Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary. J. Clin. Endocrinol. Metab.88, 879–887 (2003).
  • Gaytan F, Morales C, Barreiro ML et al. Expression of growth hormone secretagogue receptor type 1a, the functional ghrelin receptor, in human ovarian surface epithelium, mullerian duct derivatives, and ovarian tumors. J. Clin. Endocrinol. Metab.90, 1798–1804 (2005).
  • Gualillo O, Caminos JE, Blanco M et al. Ghrelin, a novel placental-derived hormone. Endocrinology142, 788–794 (2001).
  • Cortelazzi D, Cappiello V, Morpurgo PS et al. Circulating levels of ghrelin in human fetuses. Eur. J. Endocrinol.149, 111–116 (2003).
  • Tanaka K, Minoura H, Isobe T et al. Ghrelin is involved in the decidualization of human endometrial stromal cells. J. Clin. Endocrinol. Metab.88, 2335–2340 (2003).
  • Kawamura K, Sato N, Fukuda J et al. Ghrelin inhibits the development of mouse preimplantation embryos in vitro. Endocrinology144, 2623–2633 (2003).
  • Smith RG, Jiang H, Sun Y. Developments in ghrelin biology and potential clinical relevance. Trends Endocrinol. Metab.16, 436–442 (2005).
  • Garcia JM, Li H, Mann D et al. Hypogonadism in male patients with cancer. Cancer106, 2583–2591 (2006).
  • Tena-Sempere M. GPR54 and kisspeptin in reproduction. Hum. Reprod. Update12, 631–639 (2006).
  • Sirotkin AV, Grossmann R, Maria-Peon MT, Roa J, Tena-Sempere M, Klein S. Novel expression and functional role of ghrelin in chicken ovary. Mol. Cell. Endocrinol.257–258, 15–25 (2006).
  • Barreiro ML, Tena-Sempere M. Ghrelin and reproduction: a novel signal linking energy status and fertility? Mol. Cell. Endocrinol.226, 1–9 (2004).
  • Sun Y, Asnicar M, Saha PK, Chan L, Smith RG. Ablation of ghrelin improves the diabetic but not the obese phenotype of ob/ob mice. Cell Metab.3, 379–386 (2006).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.