Ghrelin: new insights into female reproductive system-associated disorders and pregnancy.

Ghrelin is considered the endogenous ligand of growth hormone secretagogue receptor type 1a, and its modulatory actions have been demonstrated in a large array of endocrine and nonendocrine functions. According to recent studies, ghrelin seems to act at different levels of the reproductive system, exerting predominantly inhibitory effects on mammalian reproduction. It has been shown to influence the reproductive system by regulating hormone secretion from the brain and by acting directly on the gonads to affect tissue development and steroidogenesis. Thus, the endocrine network, which integrates energy balance and fertility, might involve ghrelin. Furthermore, ghrelin levels and actions have been assessed in various female reproductive system disorders. The findings could lead to a better understanding of the pathogenesis of these disorders and, possibly, to more beneficial therapeutic strategies.

[1]  啓至 比江嶋 Regional distribution and the dynamics of n-decanoyl ghrelin, another acyl-form of ghrelin, upon fasting in rodents , 2010 .

[2]  A. Steiger,et al.  Ghrelin suppresses secretion of luteinizing hormone in humans. , 2007, The Journal of clinical endocrinology and metabolism.

[3]  G. Anifandis,et al.  Blockage of ghrelin-induced prolactin secretion in women by bromocriptine. , 2010, Fertility and sterility.

[4]  M. Deif,et al.  Effect of food restriction on ghrelin in adult male rats and its relation to male reproductive hormones , 2010, Andrologia.

[5]  E. Ravussin,et al.  Ghrelin and peptide YY in postpartum lactating and nonlactating women. , 2010, The American journal of clinical nutrition.

[6]  Ayla Güven,et al.  Characteristics of polycystic ovarian syndrome and relationship with ghrelin in adolescents. , 2010, Journal of pediatric and adolescent gynecology.

[7]  C. Messini,et al.  Growth hormone and prolactin response to ghrelin during the normal menstrual cycle , 2009, Clinical endocrinology.

[8]  T. Horvath,et al.  Maternal ghrelin deficiency compromises reproduction in female progeny through altered uterine developmental programming. , 2011, Endocrinology.

[9]  G. Anifandis,et al.  Effect of Ghrelin and Thyrotropin-releasing Hormone on Prolactin Secretion in Normal Women , 2009, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[10]  M. Daghestani,et al.  Circulating ghrelin levels and the polycystic ovary syndrome: correlation with the clinical, hormonal and metabolic features. , 2011, European journal of obstetrics, gynecology, and reproductive biology.

[11]  A. Sirotkin,et al.  The cAMP analogue, dbcAMP affects release of steroid hormones by cultured rabbit ovarian cells and their response to FSH, IGF-I and ghrelin. , 2010, European journal of pharmacology.

[12]  T. Kawarabayashi,et al.  Alteration of Plasma Ghrelin Levels Associated With the Blood Pressure in Pregnancy , 2002, Hypertension.

[13]  I. Papassotiriou,et al.  The Role of IGF-1 and Ghrelin in the Compensation of Intrauterine Growth Restriction , 2009, Reproductive Sciences.

[14]  V. Locatelli,et al.  Growth hormone secretagogues: focus on the growth hormone-releasing peptides. , 1997, Pharmacological research.

[15]  C. Messini,et al.  Effect of ghrelin on gonadotrophin secretion in women during the menstrual cycle. , 2008, Human reproduction.

[16]  Suna Aydin,et al.  Serum leptin and ghrelin concentrations of maternal serum, arterial and venous cord blood in healthy and preeclamptic pregnant women , 2008, Journal of Physiology and Biochemistry.

[17]  C. Simón,et al.  Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. , 2006, Fertility and sterility.

[18]  M. Furuta,et al.  Intracerebroventricular administration of ghrelin rapidly suppresses pulsatile luteinizing hormone secretion in ovariectomized rats. , 2001, Biochemical and biophysical research communications.

[19]  F. Casanueva,et al.  Effects of chronic hyperghrelinemia on puberty onset and pregnancy outcome in the rat. , 2005, Endocrinology.

[20]  N. Sato,et al.  Ghrelin inhibits the development of mouse preimplantation embryos in vitro. , 2003, Endocrinology.

[21]  L. Poston Leptin and Preeclampsia , 2002, Seminars in reproductive medicine.

[22]  M. Tena-Sempere KiSS-1 and Reproduction: Focus on Its Role in the Metabolic Regulation of Fertility , 2006, Neuroendocrinology.

[23]  M. Papotti,et al.  Ghrelin Expression in Fetal, Infant, and Adult Human Lung , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[24]  J. Kotwica,et al.  Leptin controls rabbit ovarian function in vivo and in vitro: possible interrelationships with ghrelin. , 2009, Theriogenology.

[25]  A. Lanzone,et al.  Administration of exogenous ghrelin in obese patients with polycystic ovary syndrome: effects on plasma levels of growth hormone, glucose, and insulin. , 2007, Fertility and sterility.

[26]  F. Casanueva,et al.  Role of ghrelin in reproduction. , 2007, Reproduction.

[27]  F. Valenzuela,et al.  Some endocrine traits of transgenic rabbits. II. Changes in hormone secretion and response of isolated ovarian tissue to FSH and ghrelin. , 2008, Physiological research.

[28]  J. Rivier,et al.  Decrease in luteinizing hormone pulse frequency during a five-hour peripheral ghrelin infusion in the ovariectomized rhesus monkey. , 2004, The Journal of clinical endocrinology and metabolism.

[29]  M. Tena-Sempere,et al.  Kisspeptins: Bridging energy homeostasis and reproduction , 2010, Brain Research.

[30]  Patrick R. Griffin,et al.  A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone Release , 1996, Science.

[31]  K. Kangawa,et al.  Ghrelin is involved in the decidualization of human endometrial stromal cells. , 2003, The Journal of clinical endocrinology and metabolism.

[32]  M. Tena-Sempere,et al.  Novel expression and functional role of ghrelin in chicken ovary , 2006, Molecular and Cellular Endocrinology.

[33]  K. Kangawa,et al.  Amidated fish ghrelin: purification, cDNA cloning in the Japanese eel and its biological activity. , 2003, The Journal of endocrinology.

[34]  S. Pournaras,et al.  Blood ghrelin, resistin, and adiponectin concentrations during the normal menstrual cycle. , 2009, Fertility and sterility.

[35]  A. Luger,et al.  Insulin resistance has no impact on ghrelin suppression in pregnancy , 2007, Journal of internal medicine.

[36]  Terry J. Smith,et al.  Ghrelin in the human myometrium , 2010, Reproductive biology and endocrinology : RB&E.

[37]  A. Pontecorvi,et al.  Effects of ghrelin administration on endocrine and metabolic parameters in obese women with polycystic ovary syndrome , 2007, Journal of endocrinological investigation.

[38]  E. Ghigo,et al.  Acylated ghrelin inhibits spontaneous luteinizing hormone pulsatility and responsiveness to naloxone but not that to gonadotropin-releasing hormone in young men: evidence for a central inhibitory action of ghrelin on the gonadal axis. , 2008, The Journal of clinical endocrinology and metabolism.

[39]  M. Górska,et al.  Ghrelin in gestational diabetes: serum level and mRNA expression in fat and placental tissue. , 2010, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[40]  H. Li,et al.  Expression of the orexigenic peptide ghrelin and the type 1a growth hormone secretagogue receptor in sheep oocytes and pre-implantation embryos produced in vitro. , 2010, Reproduction in domestic animals = Zuchthygiene.

[41]  K. Toshinai,et al.  Maternal ghrelin plays an important role in rat fetal development during pregnancy. , 2006, Endocrinology.

[42]  A. Sirotkin,et al.  Comparison of effects of leptin and ghrelin on porcine ovarian granulosa cells. , 2010, Domestic animal endocrinology.

[43]  J. Vrbíková,et al.  Obesity and Polycystic Ovary Syndrome , 2009, Obesity Facts.

[44]  A. Steiger,et al.  Ghrelin suppresses secretion of FSH in males , 2009, Clinical endocrinology.

[45]  E. Gregoraszczuk,et al.  Effect of ghrelin on proliferation, apoptosis and secretion of progesterone and hCG in the placental JEG-3 cell line. , 2010, Reproductive biology.

[46]  A. Sirotkin,et al.  Effects of ghrelin and its analogues on chicken ovarian granulosa cells. , 2008, Domestic animal endocrinology.

[47]  R. Pierson,et al.  Metabolic fuel and clinical implications for female reproduction. , 2007, Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC.

[48]  N. Yilmaz,et al.  Ghrelin and adiponectin levels in colostrum, cord blood and maternal serum , 2010, Pediatrics international : official journal of the Japan Pediatric Society.

[49]  F. Valenzuela,et al.  Role of ghrelin in regulating rabbit ovarian function and the response to LH and IGF-I. , 2009, Domestic animal endocrinology.

[50]  K. Kangawa,et al.  Bullfrog Ghrelin Is Modified by n-Octanoic Acid at Its Third Threonine Residue* , 2001, The Journal of Biological Chemistry.

[51]  M. Thorner,et al.  Effects of glucose and insulin on acyl ghrelin and desacyl ghrelin, leptin, and adiponectin in pregnant women with diabetes. , 2010, Metabolism: clinical and experimental.

[52]  P. Georgoulias,et al.  Current and potential roles of ghrelin in clinical practice , 2010, Journal of endocrinological investigation.

[53]  N. Tawadros,et al.  Facilitation of decidualization by locally produced ghrelin in the human endometrium. , 2007, Molecular human reproduction.

[54]  M. Nakazato,et al.  Ghrelin in neonatal rats: distribution in stomach and its possible role. , 2002, The Journal of endocrinology.

[55]  S. Bernasconi,et al.  Ghrelin inhibits steroid biosynthesis by cultured granulosa-lutein cells. , 2008, The Journal of clinical endocrinology and metabolism.

[56]  E. Arvat,et al.  Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin in humans , 2003, Journal of endocrinological investigation.

[57]  P. Szczerbik,et al.  The effects of ghrelin on the in vitro spontaneous and sGnRH-A stimulated luteinizing hormone (LH) release from the pituitary cells of common carp (Cyprinus carpio L.). , 2009, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[58]  G. Winkler,et al.  Elevated serum acylated (biologically active) ghrelin and resistin levels associate with pregnancy-induced weight gain and insulin resistance. , 2007, Diabetes research and clinical practice.

[59]  C. Schöfl,et al.  Circulating ghrelin levels in patients with polycystic ovary syndrome. , 2002, The Journal of clinical endocrinology and metabolism.

[60]  M. J. Vazquez,et al.  Comparative analysis of the effects of ghrelin and unacylated ghrelin on luteinizing hormone secretion in male rats. , 2006, Endocrinology.

[61]  M. Thorner,et al.  Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase. , 2009, American journal of physiology. Endocrinology and metabolism.

[62]  M. Nakazato,et al.  Ghrelin is a growth-hormone-releasing acylated peptide from stomach , 1999, Nature.

[63]  T. Mizushima,et al.  Structural Divergence of Human Ghrelin , 2003, The Journal of Biological Chemistry.

[64]  S. Aydin The presence of the peptides apelin, ghrelin and nesfatin-1 in the human breast milk, and the lowering of their levels in patients with gestational diabetes mellitus , 2010, Peptides.

[65]  J. Frystyk,et al.  Ghrelin and its relationship to growth hormones during normal pregnancy , 2005, Clinical endocrinology.

[66]  N. Georgopoulos,et al.  Decreased active, total and altered active to total ghrelin ratio in normal weight women with the more severe form of polycystic ovary syndrome. , 2010, European journal of obstetrics, gynecology, and reproductive biology.

[67]  Y. Nishi,et al.  Structures and molecular forms of the ghrelin-family peptides , 2011, Peptides.

[68]  A. Stavreus-Evers,et al.  Diminished Endometrial Expression of Ghrelin and Ghrelin Receptor Contributes to Infertility , 2010, Reproductive Sciences.

[69]  J. Sowiński,et al.  Elevated ghrelin plasma levels in patients with polycystic ovary syndrome. , 2004, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[70]  M. Tena-Sempere,et al.  Effects of Ghrelin upon Gonadotropin-Releasing Hormone and Gonadotropin Secretion in Adult Female Rats: In vivo and in vitro Studies , 2006, Neuroendocrinology.

[71]  M. Tena-Sempere Exploring the role of ghrelin as novel regulator of gonadal function. , 2005, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[72]  S. Pournaras,et al.  The effect of estrogens on plasma ghrelin concentrations in women , 2010, Journal of endocrinological investigation.