Downregulation of prolactin-releasing peptide gene expression in the hypothalamus and brainstem of diabetic rats.
ABSTRACT 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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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 · 0.85 Impact Factor
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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 · 4.24 Impact Factor
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ABSTRACT: Abstract: Prolactin-releasing peptide (PrRP) was first isolated from bovine hypothalamus as an orphan G-protein-coupled receptor using the strategy of reverse pharmacology. PrRP is expressed specifically in the human pituitary and is identified in the hypothalamus as a potent prolactin-releasing factor (PRF) for anterior pituitary cells. The initial studies showed that PrRP was a potent and specific prolactin-releasing factor; however our studies in the pituitary demonstrated that PrRP is more important such as modulator of prolactin release mediated by thyroid-releasing hormone (TRH) than PRF itself. However, physiological studies indicated that PrRP might play a wide range of roles in neuroendocrinology other than prolactin release, i.e., sleep regulation, metabolic homeostasis, food intake, stress responses or cardiovascular regulation. Over 150 papers and several patents have been published on this subject since its initial discovery in 1998. Herein, I review the state of current knowledge of the PrRP system, especially its roles in brain functions and implications for therapy.Immunology Endocrine & Metabolic Agents - Medicinal Chemistry (Formerly Current Medicinal Chemistry - Immunology Endocrine & Metabolic Agents) 09/2011; 11. DOI:10.2174/187152211796642792