Article

Leptin signaling and circuits in puberty and fertility

Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Y6-220B, Dallas, TX, 75390-9077, USA, .
Cellular and Molecular Life Sciences CMLS (Impact Factor: 5.86). 08/2012; 70(5). DOI: 10.1007/s00018-012-1095-1
Source: PubMed

ABSTRACT Leptin is an adipocyte-derived hormone involved in a myriad of physiological process, including the control of energy balance and several neuroendocrine axes. Leptin-deficient mice and humans are obese, diabetic, and display a series of neuroendocrine and autonomic abnormalities. These individuals are infertile due to a lack of appropriate pubertal development and inadequate synthesis and secretion of gonadotropins and gonadal steroids. Leptin receptors are expressed in many organs and tissues, including those related to the control of reproductive physiology (e.g., the hypothalamus, pituitary gland, and gonads). In the last decade, it has become clear that leptin receptors located in the brain are major players in most leptin actions, including reproduction. Moreover, the recent development of molecular techniques for brain mapping and the use of genetically modified mouse models have generated crucial new findings for understanding leptin physiology and the metabolic influences on reproductive health. In the present review, we will highlight the new advances in the field, discuss the apparent contradictions, and underline the relevance of this complex physiological system to human health. We will focus our review on the hypothalamic circuitry and potential signaling pathways relevant to leptin's effects in reproductive control, which have been identified with the use of cutting-edge technologies of molecular mapping and conditional knockouts.

0 Followers
 · 
139 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Leptin is primarily expressed in white adipose tissue; however, it is expressed in the hypothalamus and reproductive tissues as well. Leptin acts by activating the leptin receptors (Ob-Rs). Additionally, the regulation of several neuroendocrine and reproductive functions, including the inhibition of glucocorticoids and enhancement of thyroxine and sex hormone concentrations in human beings and mice are leptin functions. It has been suggested that thyroid hormones (TH) could directly regulate leptin expression. Additionally, hypothyroidism compromises the intracellular integration of leptin signaling specifically in the arcuate nucleus. Two TH receptor isoforms are expressed in the testis, TRa and TRb, with TRa being the predominant one that is present in all stages of development. The effects of TH involve the proliferation and differentiation of Sertoli and Leydig cells during development, spermatogenesis, and steroidogenesis. In this context, TH disorders are associated with sexual dysfunction. An endocrine and/or direct paracrine effect of leptin on the gonads inhibits testosterone production in Leydig cells. Further studies are necessary to clarify the effects of both hormones in the testis during hypothyroidism. The goal of this review is to highlight the current knowledge regarding leptin and TH in the testis.
    Frontiers in Endocrinology 11/2014; 5:198. DOI:10.3389/fendo.2014.00198
  • [Show abstract] [Hide abstract]
    ABSTRACT: Leptin was known as a pivotal regulator for the control of food intake and energy expenditure. However, leptin has also been found to be involved in the regulation of female reproductive system through interactions with pathways in the hypothalamic-hypophyseal axis and direct action at the ovarian level. In the present study, granulosa cells from goose ovarian preovulatory (F1-F3) follicles were cultured with leptin (0, 1, 10 or 100 ng/ml). The proliferative and anti-apoptotic actions of leptin in granulosa cells were revealed by CCK-8, BrdU and TUNEL assays. Quantitative real-time PCR and Western blot analyses further indicated that leptin treatment led to increased expression of cyclin D1, cyclin D2, cyclin D3 and bcl-2, and decreased expression of p21 and caspase-3. The effects were involved in the activation of the PI3K/Akt/mTOR signaling pathway, as leptin treatment enhanced the expression of PI3K, Akt1, Akt2, Raptor, mTOR, S6K and p-S6K. Moreover, blockade of the PI3K/Akt/mTOR pathway attenuated the influences of leptin on proliferation and apoptosis of granulosa cells, considering that activated factors by leptin were inhibited in the presence of either 20 μM LY294002 (a PI3K inhibitor) or 10 μM rapamycin (an mTOR inhibitor). In addition, leptin had a modulatory effect on the expression of its receptor at the transcriptional and translational levels, and blockade of PI3K/Akt/mTOR inhibited both basal and leptin-induced Lepr gene and protein expression. These findings suggest that leptin exerts its proliferative and anti-apoptotic effects on goose granulosa cells through the PI3K/Akt/mTOR signaling pathway via interaction with its receptor. Copyright © 2015. Published by Elsevier Ltd.
    The Journal of Steroid Biochemistry and Molecular Biology 01/2015; 149. DOI:10.1016/j.jsbmb.2015.01.001 · 4.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Puberty and adolescence are key developmental processes occurring in the transition period between childhood and adulthood. They involve respectively profound physical and behavioral changes that share dependency on maturational events in the central nervous system (CNS). The neurobiology and endocrinology of puberty and adolescence has made important progress during the past decade through finely tuned studies on behavior, CNS imaging and molecular neurobiology. The aim of this volume is to provide the readers with a pathophysiological perspective on the role of CNS in puberty and adolescence, starting from genetic/molecular aspects, going through structural/imaging changes and leading to physical/behavioral characteristics. Therefore, renowned investigators involved in both animal and human research shared recent data as well as overall appraisal of relevant questions around CNS control of puberty and adolescence. No doubt that this volume will inspire those involved in either scientific research or clinical practice or both in the fascinating field of puberty and adolescence.
    Brain Crosstalk in Puberty and Adolescence, Edited by Jean-Pierre Bourguignon, Jean-Claude Carel, Yves Christen, 01/2015: chapter The Adolescent Brain: Insights from Neuroimaging: pages 85-96; Springer., ISBN: 9783319091679

Preview

Download
2 Downloads
Available from