Leptin and reproduction: a review

Moschos, Stergios; Chan, Jean L; Mantzoros, Christos S

doi:10.1016/s0015-0282(01)03010-2

Cited by 557Hypothalamic control of reproductive hormonesRegulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic Diseases

Leptin and reproduction: a review

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Moschos, Stergios, Chan, Jean L, Mantzoros, Christos S·2002·Fertility and Sterility

DOI 10.1016/s0015-0282(01)03010-2

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Abstract

Objective To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations.Design A MEDLINE computer search was performed to identify relevant articles.Result(s) Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions.Conclusion(s) Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.

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Our findings lend further credence to converging lines of evidence from animal models and observational studies in humans indicating an important role of leptin in reproduction.
“Our findings lend further credence to converging lines of evidence from animal models and observational studies in humans indicating an important role of leptin in reproduction (28).”
From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [28]

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Leptin Concentrations in the Polycystic Ovary Syndrome
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Cerebrospinal Fluid Leptin in Anorexia Nervosa: Correlation with Nutritional Status and Potential Role in Resistance to Weight Gain1
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Interleukin 1α Increases Serum Leptin Concentrations in Humans
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Plasma leptin in female athletes: relationship with body fat, reproductive, nutritional, and endocrine factors.
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Effect of Puberty on the Relationship between Circulating Leptin and Body Composition
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Role of Leptin in Reproduction
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Neonatal Cord Blood Leptin: Its Relationship to Birth Weight, Body Mass Index, Maternal Diabetes, and Steroids
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Chronic administration of neuropeptide Y into the lateral ventricle inhibits both the pituitary-testicular axis and growth hormone and insulin-like growth factor I secretion in intact adult male rats
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Adipose Obese Gene Product, Leptin, Inhibits Bovine Ovarian Thecal Cell Steroidogenesis1
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Pubertal adipose tissue: is it necessary for normal sexual maturation? Evidence from the rat and human female.
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Serum Leptin Levels in Women with Polycystic Ovary Syndrome: The Role of Insulin Resistance/ Hyperinsulinemia
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Decreased Leptin Levels in Normal Weight Women with Hypothalamic Amenorrhea: The Effects of Body Composition and Nutritional Intake
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Putting body weight and osteoporosis into perspective
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Expression of Leptin Receptor in Human Endometrium and Fluctuation during the Menstrual Cycle
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Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity
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Leptin and Leptin Receptor Are Expressed in the Human Endometrium and Endometrial Leptin Secretion Is Regulated by the Human Blastocyst
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Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin
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Serum leptin concentration in women: effect of age, obesity, and estrogen administration
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Leptin directly stimulates aromatase activity in human luteinized granulosa cells
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Obesity and reproduction
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Galanin-Like Peptide (GALP) Is a Target for Regulation by Leptin in the Hypothalamus of the Rat
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Serum Leptin Concentrations in Women with Polycystic Ovary Syndrome
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Leptin Is Not Necessary for Gestation and Parturition But Regulates Maternal Nutrition via a Leptin Resistance State
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Chronic Administration of Leptin into the Lateral Ventricle Induces Sexual Maturation in Severely Food‐restricted Female Rats
Gruaz, N. M., Lalaoui, M., Pierroz, D. D., Englaro, P., Sizoneko, P. C., Blum, W. F., & Aubert, M. L. (1998) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1998.00247.x · Cited by 137 · see citing works
In VitroStimulation of the Prepubertal Rat Gonadotropin-Releasing Hormone Pulse Generator by Leptin and Neuropeptide Y through Distinct Mechanisms1
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Predictive value of serum and follicular fluid leptin concentrations during assisted reproductive cycles in normal women and in women with the polycystic ovarian syndrome
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Expression of a Leptin Receptor in Immortalized Gonadotropin-Releasing Hormone-Secreting Neurons
Magni, P., Vettor, R., Pagano, C., Calcagno, A., Beretta, E., Messi, E., ZANISI, M., Martini, L., & Motta, M. (1999) · Endocrinology · doi:10.1210/endo.140.4.6622 · Cited by 132 · see citing works
Relation of early menarche to high bone mineral density
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Leptin Binding Activity Changes with Age: The Link between Leptin and Puberty1
Quinton, N. D., Smith, R. F., Clayton, P., Gill, M. S., Shalet, S. M., Justice, S., Simon, S. A., Walters, S. J., Postel-Vinay, M. C., Blakemore, A. I. F., et al. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.7.5834 · Cited by 128 · see citing works
Leptin inhibits gonadotrophin-stimulated granulosa cell progesterone production by antagonizing insulin action
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Leptin Levels in Pregnant Women and Newborn Infants: Gender Differences and Reduction During the Neonatal Period
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Localization of Leptin Receptor-Like Immunoreactivity in the Corticotropes, Somatotropes, and Gonadotropes in the Ovine Anterior Pituitary1
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Changes in plasma leptin during the menstrual cycle
Riad-Gabriel, M., Jinagouda, S. D., Sharma, A., Boyadjian, R., & Saad, M. F. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1390528 · Cited by 120 · see citing works
Influence of insulin-like growth factor-1 and leptin on bone mass in healthy postmenopausal women
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Relation between Aspects of Nutritional Disturbance and Menstrual Activity in Primary Anorexia Nervosa
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Modulation of human cytotrophoblastic leptin secretion by interleukin-1alpha and 17beta-oestradiol and its effect on HCG secretion
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Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y
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Plasma leptin concentrations in postmenopausal women with osteoporosis
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Leptin in relation to resumption of menses in women with anorexia nervosa
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Differences in circulating concentrations of total, free and bound leptin relate to gender and body composition in adult humans
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The endometrium as a novel target for leptin: differences in fertility and subfertility
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Suppression of Leptin During Lactation: Contribution of the Suckling StimulusVersusMilk Production1
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Detection and regulation of leptin receptor mRNA in ovine mammary epithelial cells during pregnancy and lactation
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Does Leptin Have an Effect on Bone in Adult Women?
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Amenorrheic Bone Loss1
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Postnatal Changes of Leptin Levels in Full-Term and Preterm Neonates: Their Relation to Intrauterine Growth, Gender and Testosterone
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Leptin Modulates the Glucocorticoid-Induced Ovarian Steroidogenesis1
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Cocaine and Amphetamine‐Regulated‐Transcript Peptide Mediation of Leptin Stimulatory Effect on the Rat Gonadotropin‐Releasing Hormone Pulse Generator In Vitro
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Leptin Values in Placental Cord Blood of Human Newborns with Normal Intrauterine Growth after 30–42 Weeks of Gestation
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Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone
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Leptin Receptor in Human Term Placenta: in Situ Hybridization and Immunohistochemical Localization
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The Relationship between Leptin Concentration and Bone Metabolism in the Human Fetus
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Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain
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Leptin Concentrations in Women in the San Antonio Heart Study: Effect of Menopausal Status and Postmenopausal Hormone Replacement Therapy
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Leptin Impairs the Synergistic Stimulation by Transforming Growth Factor-β of Follicle-Stimulating Hormone-Dependent Aromatase Activity and Messenger Ribonucleic Acid Expression in Rat Ovarian Granulosa Cells1
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Correlation between circulating leptin and luteinizing hormone during the menstrual cycle in normal-weight women
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Decreased Serum Leptin Concentrations during Metformin Therapy in Obese Women with Polycystic Ovary Syndrome
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Decreased Serum Leptin in Bulimia Nervosa1
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Sex Differences in Circulating Human Leptin Pulse Amplitude: Clinical Implications
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Relationships between serum leptin level and regional bone mineral density, bone metabolic markers in healthy women
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Leptin and Neuropeptide Y Gene Expression in Human Placenta: Ontogeny and Evidence for Similarities to Hypothalamic Regulation
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Serum leptin concentrations during the menstrual cycle in normal-weight women: effects of an oral triphasic estrogen-progestin medication
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Serum leptin concentrations throughout the menstrual cycle
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Normal Reproductive Function in Leptin-Deficient Patients with Lipoatropic Diabetes
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Alterations in body composition and fat distribution in growth hormone—Deficient prepubertal children during growth hormone therapy
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Sex-based differences in serum leptin concentrations from umbilical cord blood at delivery
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Hypoleptinaemia in Patients With Anorexia Nervosa and in Elite Gymnasts With Anorexia Athletica
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Hypoleptinemia in female and male elite gymnasts
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Effects of anabolic-androgenic steroid use or gonadal testosterone suppression on serum leptin concentration in men
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Identification and expression analysis of leptin-regulated immediate early response and late target genes
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Leptin in Postmenopausal Women: Influence of Hormone Therapy, Insulin, and Fat Distribution
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Serum leptin levels during the menstrual cycle of healthy fertile women.
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The Effect of Leptin on Luteinizing Hormone Release Is Exerted in the Zona Incerta and Mediated by Melanin‐Concentrating Hormone
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Decreased Serum Leptin in Bulimia Nervosa
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Reduced plasma leptin concentrations in bulimia nervosa
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Growth Pattern and Age at Menarche of Obese Girls in a Transitional Society
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Interactive effects of central leptin and peripheral fuel oxidation on estrous cyclicity
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Cellular Mechanism of Pulsatile LHRH Release1
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Regulation of Gonadal and Somatotropic Axis by Chronic Intraventricular Infusion of Insulin-Like Growth Factor 1 Antibody at the Initiation of Puberty in Male Rats
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Changes in Leptin Concentration during the Early Postnatal Period: Adjustment to Extrauterine Life?
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Authors: Moschos, S., Chan, J. L., & Mantzoros, C. S.
Affiliations: Beth Israel Deaconess Medical Center (US)
Corresponding author: Mantzoros, Christos S
ORCID: Moschos, Stergios
Mantzoros, Christos S
Venue: Fertility and Sterility
Publisher: Elsevier BV
Published: 2002-03
Volume: 77
Issue: 3
Pages: 433-444
ISSN: 0015-0282 (ISSN-L)
DOI: 10.1016/s0015-0282(01)03010-2
OpenAlex: W2058073773
Cited by: 557
References: 180
Citations by year: 2026: 9 · 2025: 13 · 2024: 12 · 2023: 12 · 2022: 21 · 2021: 16 · 2020: 20 · 2019: 24 · 2018: 14 · 2017: 19 · 2016: 26 · 2015: 26 · 2014: 27 · 2013: 37 · 2012: 26
FWCI: 6.29
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 7392 d)
Locations: Fertility and Sterility (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: leptin, reproduction, hypothalamic-pituitary-gonadal axis, energy homeostasis, puberty, amenorrhea, eating disorders, exercise-induced amenorrhea, functional hypothalamic amenorrhea, obesity, polycystic ovary syndrome, leptin resistance, leptin deficiency, endometrium, placenta, mammary gland, lactation, pregnancy, gonadotropins, growth hormone
MeSH terms: Adipose Tissue, Female, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Pregnancy, Reproduction, Leptin

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