From feeding one to feeding many: hormone‐induced changes in bodyweight homeostasis during pregnancy

Abstract

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 α-melanocyte-stimulating hormone (α-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.

Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation

“…Furthermore, ERb is highly expressed throughout the HF, including the bulge region (Ohnemus et al 2006). Like Prl, estrogen levels increase during pregnancy (Augustine et al 2008), which may contribute to the alterations in HF growth during pregnancy. Estrogen has been suggested to induce Prl and Prlr expression in cultured human skin (Langan et al 2010), but further work is needed to elucidate whether Prl and estrogen act synergistically to modulate murine hair growth dynamics during the native or pregnant hair cycle.…”

“…3D; Augustine et al 2008), we next analyzed p-Stat5 activity in the skin of pregnant and lactating mice. We found high p-Stat5 activity in bulge SCs during pregnancy and lactation and little to no detectable p-Stat5 in the HG (Fig.…”

“…To test this hypothesis, hair regrowth was analyzed in mice treated with BRC during lactation. We administered a low dose of BRC by subcutaneous injection to reduce systemic Prl levels at a time when it is continually elevated without terminating lactation (Augustine et al 2008). Females in the extended telogen phase of the hair cycle were shaved at the initiation of pregnancy, and hair regrowth was monitored externally throughout pregnancy and lactation and after weaning (Fig.…”

“…Several hormones are altered during pregnancy and lactation (Augustine et al 2008), yet the precise molecular mechanisms that modulate HF SC activity during these physiological states remain unclear. Prolactin (Prl) is highly elevated during pregnancy and lactation, and several lines of evidence have implicated a function for Prl signaling in the control of hair growth outside of pregnancy.…”

Obesity and energy balance: is the tail wagging the dog?

“…hormonally regulated, including pregnancy weight gain (Augustine et al, 2008) and childhood growth (Bogin, 1999). Second, since the 1930s, European clinicians have used insulin and carbohydrate to fatten underweight patients (Taubes, 2008), demonstrating a consistent effect of insulin across a wide range of body weight.…”