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.

12 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Carnitine is involved in fatty acid metabolism in mammals and is widely used as a nutritional supplement; carnitine orotate is a more absorbable form of carnitine. We investigated the effects of carnitine and carnitine orotate on mouse prolactin-releasing peptide (PrRP) mRNA expression. Twenty-four female mice were randomly divided into four groups of six; control mice were orally drenched with physiological saline solution (250 mg/kg body weight) and treatment mice were orally drenched with carnitine (250 mg/kg) or carnitine orotate (250 or 750 mg/kg), once a day, for 20 days from parturition. The carnitine or carnitine orotate was dissolved in saline solution before administration. The hypothalamus, pituitary and ovary were sampled on day 21 after parturition, and PrRP mRNA levels in these tissues were measured by semi-quantitative PCR, with glyceraldehyde 3-phosphate dehydrogenase as a control. Expression of PrRP in mice treated with carnitine and carnitine orotate was significantly increased in the ovary and significantly reduced in the pituitary gland. Compared with the control, hypothalamus PrRP mRNA increased significantly in the carnitine and low-dose carnitine orotate groups and decreased significantly in the high-dose carnitine orotate group. We conclude that carnitine and carnitine orotate regulate expression of PrRP in the pituitary gland and ovaries.
    Genetics and molecular research: GMR 01/2011; 10(4):3013-9. DOI:10.4238/2011.December.6.1 · 0.78 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Poorly controlled diabetes is associated with hormonal imbalances, including decreased prolactin production partially due to increased lactotroph apoptosis. In addition to its metabolic actions, ghrelin inhibits apoptosis in several cell types. Thus, we analyzed ghrelin's effects on diabetes-induced pituitary cell death and hormonal changes. Six weeks after onset of diabetes in male Wistar rats (streptozotocin 70 mg/kg), minipumps infusing saline or 24 nmol ghrelin/day were implanted (jugular). Rats were killed two weeks later. Ghrelin did not modify body weight or serum glucose, leptin or adiponectin, but increased total ghrelin (P<0.05), IGF-I (P<0.01) and prolactin (P<0.01) levels. Ghrelin decreased cell death, iNOS and active caspase-8 (P<0.05) and increased prolactin (P<0.05), Bcl-2 (P<0.01) and Hsp70 (P<0.05) content in the pituitary. In conclusion, ghrelin prevents diabetes-induced death of lactotrophs, decreasing caspase-8 activation and iNOS content and increasing anti-apoptotic pathways such as pituitary Bcl-2 and Hsp70 and serum IGF-I concentrations.
    Molecular and Cellular Endocrinology 06/2009; 309(1-2):67-75. DOI:10.1016/j.mce.2009.06.006 · 4.41 Impact Factor
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Oxytocin has potent central effects on feeding behaviour, as well as on social and sexual behaviours, and one likely substrate for its anorectic effect is the ventromedial nucleus of the hypothalamus. This nucleus expresses a high density of oxytocin receptors, but contains very few oxytocin-containing fibres, hence it is a likely target of 'neurohormonal' actions of oxytocin, including possibly oxytocin released from the dendrites of magnocellular oxytocin neurones. As oxytocin release from dendrites is regulated independent of electrical activity and of secretion from the neurohypophysis, exactly how this release is regulated by metabolic and reproduction-related signals remains to be established fully. Intriguingly though, it looks as though this central release of oxytocin from magnocellular neurons might be instrumental in a fundamental shift in motivational behaviour - switching behaviour from being driven by the need to find and consume food, to the need to reproduce.
    Progress in brain research 01/2008; 170:137-51. DOI:10.1016/S0079-6123(08)00413-5 · 2.83 Impact Factor
Show more