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The role of leptin→STAT3 signaling in neuroendocrine function: an integrative perspective

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Abstract

The hormone leptin is secreted by adipose tissue in proportion to fat mass to signal the repletion of body energy stores to the neuroendocrine system. Leptin acts on neurons in the hypothalamus and elsewhere in the brain to decrease appetite and regulate the activity of the thyroid, adrenal, growth, gonadal, and lactational axes. Conversely, absence of leptin signaling initiates the neuroendocrine starvation response. Leptin mediates these effects by activating the long form (LRb) of its receptor. One LRb signal, STAT3, has recently been shown to play a critical role in the regulation of body weight and some elements of neuroendocrine function (thyroid, adrenal, lactation), although the participation of STAT3 in the gonadal and growth axes is negligible. We discuss these findings in the context of the hypothalamic neuroendocrine system as it is presently understood.

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Abbreviations

AgRP :

Agouti-related peptide

ARC :

Arcuate nucleus

CRH :

Corticotropin-releasing hormone

ERK :

Extracellular signal regulated kinase

GH :

Growth hormone

GHRH :

Growth hormone releasing hormone

GnRH :

Gonadotropin-releasing hormone

LR :

Leptin receptor

MCR :

Melanocortin receptor

MSH :

Melanocyte stimulating hormone

NPY :

Neuropeptide Y

POMC :

Pro-opiomelanocortin

PVH :

Paraventricular hypothalamus

SH :

Src homology

SHP :

Src homology 2 containing phosphatase

SOCS :

Suppressor of cytokine signaling

STAT :

Signal transducer and activator of transcription

TRH :

Thyrotropin-releasing hormone

VMH :

Ventromedial hypothalamus

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Acknowledgements

This research was supported by NIH DK56731 and DK 57768 and grants from the American Diabetes Association (to M.G.M.) and an American Diabetes Association/European Association for the Study of Diabetes Transatlantic Fellowship (to S.H.B.). We thank Michael Schwartz, M.D. for helpful discussions.

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  1. Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA

    Sarah H. Bates & Martin G. Myers

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Correspondence to Martin G. Myers.

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Bates, S.H., Myers, M.G. The role of leptin→STAT3 signaling in neuroendocrine function: an integrative perspective. J Mol Med 82, 12–20 (2004). https://doi.org/10.1007/s00109-003-0494-z

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