STREPTOZOTOCIN-INDUCED DIABETES PRODUCES A DECREASE IN PITUITARY SUBSTANCE-P CONTENT AND PREPROTACHYKININ MESSENGER-RNA

Complications arising from diabetes mellitus include hormonal dysfunct ions such as impairment in the regulation of gonadatroph and corticotr oph secretion. Preprotachykinin (PPT) mRNA encoding the peptide substa nce P (SP), has been localized in the anterior pituitary. The goal of this study was to determine if streptozotocin (STZ)-induced diabetes a ffects the SP content or PPT mRNA level in the pituitary of male rats. We injected STZ (55 mg/kg) to 6-week-old rats which developed hypergl ycemia (blood glucose > 400 mg/dl) by 6 weeks post-injection. SP-like immunoreactivity in the pituitary dropped 54%. In situ hybridization w as performed using a PPT-specific oligonucleotide with signal intensit y differences semi-quantified using an image analysis system. Normal p ituitary had a regional distribution of PPT mRNA, with no detectable s ignal in the posterior or intermediate lobes, while the anterior lobe displayed a distinctive pattern of labeled cells arranged in dusters. In diabetic rats there was a 23% decrease in the PPT-mRNA hybridizatio n signal compared to controls (P < 0.05). The changes observed in PPT gene expression and SP content may be additional factors participating in the hormonal complications seen in diabetes mellitus.