ReviewLeptin and reproductive function
Highlights
► Leptin alters secretion of gonadotropin hormones essential for normal reproduction. ► Leptin regulates hypothalamic gonadotropin-releasing hormone neuronal activity. ► Leptin affects on GnRH are mediated by NPY, proopiomelanocortin and kisspeptin. ► Kisspeptin-GnRH pathway mediates infertility due to obesity or leptin resistance. ► Adipose tissue leptin may be involved in leptin's influence on reproduction.
Section snippets
Adipose tissue as an endocrine organ
Adipose tissue plays a dynamic role in physiological mechanisms and whole-body homeostasis. The role of adipose tissue includes responding to a variety of signals and subsequently secreting factors or “adipokines” that have important roles in physiology [1]. Current evidence indicates that many of the adipose tissue “adipokines, can be considered true endocrine factors [2]. Therefore, adiposity could impact physiological states, such as reproductive condition or status, through secretion of
Leptin: a metabolic signal and puberty
Metabolic signals are considered important in the initiation of puberty [24], [25], [26]. Identification of these signals has, however, remained elusive primarily due to the large number of substances originating peripherally that can act centrally to modify gonadotropin-releasing hormone (GnRH) neuronal activity. The discovery of leptin has improved our understanding of the relationship between adipose tissue, energy homeostasis and puberty [27]. Leptin treatment advanced sexual maturation in
Leptin secretion and reproductive state
Changes in body weight or nutritional status are characterized by alterations in serum levels of many hormones and growth factors that regulate adipocyte function and development, such as insulin, glucocorticoids, growth hormone (GH) and IGF-I [3], [41], [45]. In vivo studies demonstrated that increased leptin gene expression followed administration of glucocorticoids or insulin, suggesting that hormonal factors may mediate nutritionally induced changes in secretion of leptin [46], [47].
Central effect of leptin on the hypothalamic-pituitary axis
Acute intracerebroventricular (ICV) administration of leptin increased LH secretion in the estrogen primed OVX rat [54] and steroid implanted castrate male sheep [55]. Additionally, chronic ICV leptin treatment stimulated LH secretion in feed restricted OVX cows [43] and ewes [44]. In contrast, chronic ICV leptin treatment failed to stimulated LH secretion in well nourished OVX ewes with no steroid replacement [56], and in intact ewe lambs [42]. Leptin treatment stimulated basal and
Leptin and ovarian function
Leptin receptors have also been identified in both granulosa and theca cells of the human [103], [104] bovine [105], [106] and porcine [107] ovarian follicles. Several in vitro studies demonstrated that treatment with supraphysiological concentrations of leptin inhibited steroidogenesis in bovine granulosa [105], [108] and theca cells [106]. Similar results were reported for the human [109], [110], rat [111], sheep [112] and pig [113]. In contrast, physiological doses of leptin stimulated
Conclusion
Leptin is a key metabolic signal synthesized and secreted by fat cells that communicates information about body energy reserves, nutritional state, and metabolic shifts to the reproductive axis. Leptin can act peripherally at the ovary or centrally at the hypothalamus (Fig. 1) to augment reproductive function of females. Kisspeptin neurons are a key part of the central pathway by which leptin affects gonadotropin secretion. Hypogonadotropism and infertility observed in animal models with severe
Acknowledgments
We thank Linda Parnell for assisting in preparation of the manuscript.
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