Streptozotocin-induced diabetes produces a decrease in pituitary substance P content and preprotachykinin mRNA.
Complications arising from diabetes mellitus include hormonal dysfunctions such as impairment in the regulation of gonadatroph and corticotroph secretion. Preprotachykinin (PPT) mRNA encoding the peptide substance P (SP), has been localized in the anterior pituitary. The goal of this study was to determine if streptozotocin (STZ)-induced diabetes affects 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 hyperglycemia (blood glucose > 400 mg/dl) by 6 weeks post-injection. SP-like immunoreactivity in the pituitary dropped 54%. In situ hybridization was performed using a PPT-specific oligonucleotide with signal intensity differences semi-quantified using an image analysis system. Normal pituitary had a regional distribution of PPT mRNA, with no detectable signal in the posterior or intermediate lobes, while the anterior lobe displayed a distinctive pattern of labeled cells arranged in clusters. In diabetic rats there was a 23% decrease in the PPT-mRNA hybridization 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.
Rittenhouse
P A
PA
Department of Pharmacology, Boston University Medical Center, MA 02118-2394, USA.
Markle
R A
RA
Marchand
J E
JE
Kream
R M
RM
Leeman
S E
SE
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007328:Insulin / Q000494:pharmacology; D008297:Male; D015345:Oligonucleotide Probes; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*; D015320:Tachykinins / Q000096:biosynthesis*
D007004:Hypoglycemic Agents; D007328:Insulin; D015345:Oligonucleotide Probes; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P