Hypothalamic Sites of Leptin Action Linking Metabolism and Reproduction

• Published in: Neuroendocrinology Vol. 93; no. 1; pp. 9 - 18
• Main Authors: Donato, Jr, José, Cravo, Roberta M., Frazão, Renata, Elias, Carol F.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.02.2011; S. Karger AG
• Subjects: Animals; At the Cutting Edge; Biological and medical sciences; Brain Stem - metabolism; Brain Stem - physiology; Fundamental and applied biological sciences. Psychology; Humans; Hypothalamus - metabolism; Hypothalamus - physiology; Leptin - metabolism; Leptin - physiology; Metabolism - physiology; Neurons - metabolism; Neurons - physiology; Reproduction - physiology; Vertebrates: endocrinology; Luteinizing hormone; Gonadotropin-releasing hormone; Hypothalamus; Metabolism; Hypothalamus-pituitary-gonad axis; Endocrine gland; Genital system; Central nervous system; Gonadotropin RH; Adipokine; Encephalon; Hypothalamic hormone; Reproduction; Adenohypophyseal hormone; Gonad; Leptin; Pituitary gland; Hormone releasing factor
• ISSN: 0028-3835; 1423-0194; 1423-0194
• DOI: 10.1159/000322472

A critical amount of energy reserve is necessary for puberty initiation, for normal sexual maturation and maintenance of cyclicity and fertility in females of most species. Therefore, the existence of circulating metabolic cues which directly modulate the hypothalamus-pituitary-gonad axis is predictable. The adipocyte-derived hormone leptin is one of these cues having been studied extensively in the context of regulating the reproductive physiology. Humans and mice lacking leptin (ob/ob) or leptin receptor (LepR, db/db) are infertile. Leptin administration to leptin-deficient subjects and ob/ob mice induces puberty and restores fertility. LepR is expressed in brain, pituitary gland and gonads, but studies using genetically engineered mouse models determined that the brain plays a major role. Recently, it has been made clear that leptin acts indirectly on gonadotropin-releasing hormone (GnRH)-secreting cells via actions on interneurons. However, the exact site(s) of leptin action has been difficult to determine. In this review, we discuss the recent advances in the field focused on the identification of potential site(s) or specific neuronal populations involved in leptin’s effects in the neuroendocrine reproductive axis.