From feeding one to feeding many: hormone-induced changes in bodyweight homeostasis during pregnancy.
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 alpha-melanocyte-stimulating hormone (alpha-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.
Augustine
Rachael A
RA
Centre for Neuroendocrinology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand.
Ladyman
Sharon R
SR
Grattan
David R
DR
D000818:Animals; D001835:Body Weight / Q000502:physiology*; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D020738:Leptin / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011555:Pseudopregnancy / Q000503:physiopathology; D051381:Rats
D020738:Leptin