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This Article Full Text Full Text (PDF) All Versions of this Article: 586/2/387    most recent jphysiol.2007.146316v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Augustine, R. A. Articles by Grattan, D. R. Search for Related Content PubMed PubMed Citation Articles by Augustine, R. A. Articles by Grattan, D. R. Related Collections Review articles Neuroscience

¹ Centre for Neuroendocrinology, and Department of Anatomy and Structural Biology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand

Pregnancy is associated with hyperphagia, increased fat mass, hyperleptinaemia and hyperprolactinaemia. The neuroendocrine control of bodyweight involves appetite-regulating centres in the hypothalamus, containing both orexigenic and anorexigenic neurons that express leptin receptors (LepR). In the rat, central leptin resistance develops during mid pregnancy, well after hyperphagia becomes apparent, to negate the appetite suppressing effects of leptin. We have investigated the hypothalamic response to leptin during pregnancy and examined the role of pregnancy hormones in inducing these changes. We have shown that there are multiple levels of leptin resistance during pregnancy. Despite elevated serum leptin, neuropeptide Y and agouti related peptide mRNA in the arcuate nucleus are not suppressed and may even be increased during pregnancy. LepR mRNA and leptin-induced pSTAT3 expression, however, are relatively normal in the arcuate nucleus. In contrast, both LepR and leptin-induced pSTAT3 are reduced in the ventromedial hypothalamic nucleus. Injecting -melanocyte-stimulating hormone (-MSH) into the brain, to bypass the first-order leptin-responsive neurons in the arcuate nucleus, also fails to suppress food intake during pregnancy, suggesting that pregnancy is also a melanocortin-resistant state. Using a pseudopregnant rat model, we have demonstrated that in addition to the changes in maternal ovarian steroid secretion, placental lactogen production is essential for the induction of leptin resistance in pregnancy. Thus, hormonal changes associated with pregnancy induce adaptive changes in the maternal hypothalamus, stimulating food intake and then allowing elevated food intake to be maintained in the face of elevated leptin levels, resulting in fat deposition to provide energy stores in preparation for the high metabolic demands of late pregnancy and lactation.

(Received 8 October 2007; accepted after revision 16 November 2007; first published online 22 November 2007)
Corresponding author D. Grattan: Department of Anatomy and Structural Biology, University of Otago, PO Box 913, Dunedin, New Zealand. Email: dave.grattan{at}anatomy.otago.ac.nz

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