Neuroendocrine actions and regulation of hypothalamic neuropeptide Y during lactation

Abstract

The expression of neuropeptide Y (NPY) and its co-messenger, agouti-related peptide (AgRP), in arcuate neurons of the hypothalamus is increased during lactation in rats. Our research has been addressing the questions of the physiological actions of these peptides during lactation and the physiological signals associated with lactation that result in increased expression of their genes. Our studies indicate that NPY and AgRP exert pleiotropic actions during lactation that help integrate neuroendocrine regulation of energy balance with controls over anterior and posterior pituitary hormone secretion. Further, reciprocal signaling to the NPY/AgRP system by leptin and ghrelin is responsible for the changes in expression of these hypothalamic peptides in lactating animals, and thus, may contribute to regulation of food intake and the various neuroendocrine adaptations of lactation.

Gestational weight gain by reduced brain melanocortin activity affects offspring energy balance in rats

“…It seems likely that, under these 'maximized' intake conditions, MC4 receptor signalling is already completely abolished , leaving nothing left to block with SHU9119. In line with this observation is the report by Crowley et al 37,38 that mRNA expression of AgRP in the ARC is strongly upregulated, which is probably mediated by suckling. AgRP may lead to maximal suppression of brain MC receptor signalling, rendering additional pharmacological inhibition of brain MC receptors ineffective.…”

“…These effects contrast highly with those found with central infusion of NPY during pregnancy and lactation, which causes a very strong suppression of pup growth. 49 Although NPY may function to adapt maternal metabolism to the energy demands of nursing offspring, 37 an overpowering increase of NPY may result in an abrupt ending of lactation. 49 The physiological function of this may be to protect a mother from starvation if there is not enough food for both herself and her offspring during periods of famine.…”

Limits to sustained energy intake. XIII. Recent progress and future perspectives

“…The argument in the saturated neural control hypothesis was that this regulatory system in the brain may be stimulated by a number of peripheral signals. For example, in lactation there is a profound reduction in circulating leptin levels (Pickavance et al, 1998;Brogan et al, 1999;Kunz et al, 1999;Woodside et al, 2000), which potentially stimulates food intake via inhibition of neurons expressing POMC and CART (Elias et al, 1998) and stimulation of neurons expressing NPY and AgRP (Crowley et al, 2004;Crowley et al, 2007). There is a limit, however, to how much this system can be stimulated -in the case of leptin, for example, it is impossible to stimulate intake more than can be achieved by reducing the hormone levels to zero.…”

Effects of leptin infusion during peak lactation on food intake, body composition, litter growth, and maternal neuroendocrine status in female Brandt's voles (Lasiopodomys brandtii)

“…Both NPY and AgRP have both been shown previously to strongly stimulate food intake (6,22), while the POMC and cocaine-and amphetamine-regulated transcript have a wellestablished strong suppressive effect on food intake (34,78). Moreover, it has been shown that during lactation NPY and AgRP are both upregulated, while POMC is downregulated relative to nonreproducing controls (11,14,19,43,57). Consistent with some previous studies, we found that peripheral infusion of animals with recombinant murine leptin had significant effects on the gene expression levels of these key neuropeptides: NPY, AgRP, and POMC.…”

“…Most recently, the suggestion has been made that limitations on the capacity of the female to dissipate heat generated as a byproduct of food intake (heat increment of feeding) and milk synthesis (36,40,41,67) may limit food intake at peak lactation and hence lactation performance. Some studies have previously addressed the neuroendocrine changes that accompany the hyperphagia of lactation, showing, for example, that neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the hypothalamus are both upregulated, while proopiomelanocortin (POMC) is downregulated (11,14,31,43,48,57,83) relative to nonreproductive animals. A potential primary role in integrating these responses may be played by the levels of circulating adipokines such as leptin (65,67).…”