Downregulation of prolactin-releasing peptide gene expression in the hypothalamus and brainstem of diabetic rats

Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Peptides (Impact Factor: 2.62). 09/2007; 28(8):1596-604. DOI: 10.1016/j.peptides.2007.06.023
Source: PubMed


We investigated the prolactin-releasing peptide (PrRP) mRNA levels in the hypothalamus and brainstem of streptozotocin (STZ)-induced diabetic rats and fa/fa Zucker diabetic rats, using in situ hybridization histochemistry. PrRP mRNA levels in the hypothalamus and brainstem of STZ-induced diabetic rats were significantly reduced in comparison with those of control rats. PrRP mRNA levels in the diabetic rats were reversed by both insulin and leptin. PrRP mRNA levels in the fa/fa diabetic rats were significantly reduced in comparison with those of Fa/? rats. PrRP mRNA levels in the fa/fa diabetic rats were significantly increased by insulin-treatment, but did not reach control levels in the Fa/? rats. We also investigated the effect of restraint stress on PrRP mRNA levels in STZ-induced diabetic rats. The PrRP mRNA levels in the control and the STZ-induced diabetic rats increased significantly after restraint stress. The diabetic condition and insulin-treatment may affect the regulation of PrRP gene expression via leptin and other factors, such as plasma glucose level. The diabetic condition may not impair the role of PrRP as a stress mediator.

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    • "After insulin-treatment , PrRP mRNA levels in fa/fa diabetic rats were significantly increased. The diabetic condition and insulin treatment may affect the regulation of PrRP gene expression via leptin and other factors, such as plasma glucose level (Mera et al., 2007). Medullary PrRP neurons are negatively regulated by changes in lactation (presumably hormonal), and are not recruited to activation by suckling stimuli. "
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    • "However, pituitary levels of proteins involved in the intrinsic cell death pathway, including members of the Bcl-2 family, X-linked inhibitor of apoptosis (XIAP), and the effector caspases 3 and 6, are either unchanged or balanced towards cell survival (Arroba et al., 2005), with these changes being cell-type specific (Arroba et al., 2007). Increased apoptosis of lactotrophs may underlie, at least in part, the reduction in circulating PRL concentrations in poorly controlled diabetic patients or animals (Arroba et al., 2003; Boujon et al., 1995; Ikawa et al., 1992; Iranmanesh et al., 1990; Mera et al., 2007; Steger et al., 1989; Ostrom et al., 1993). This decrease in PRL could result in the reduced or delayed milk production observed in some diabetic women (Hartmann and Cregan, 2001; Neubauer et al. 1990, 1993; Neville et al., 1988) and streptozotocin-induced diabetic rats (Ikawa et al., 1992; Lau et al., 1993). "
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    • "CCK-induced anorexia was blocked in PrRP-KO mice, consistent with the conclusion that PrRP relays satiety signalling within the brain (Bechtold and Luckman, 2006). Furthermore, expression of PrRP mRNA is reduced in hyperphagic conditions such as lactation in rats (Bechtold and Luckman, 2007), and in streptozotocin-induced diabetic or Zucker diabetic rats (Mera et al., 2007). "
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