DIFFERENTIAL RESPONSE OF NEUROPEPTIDE-Y, SUBSTANCE-P AND VASOACTIVE INTESTINAL POLYPEPTIDE IN THE RAT ANTERIOR-PITUITARY GLAND TO ALTERATIONS IN THYROID-HORMONE STATUS

We have compared the effects of thyroidectomy with those of thyroxine (T-4) replacement and excess T-4 treatment on neuropeptide Y (NPY) in the rat anterior pituitary, and compared these with the effects on sub stance P (SP) and vasoactive intestinal peptide (VIP). Thyroidectomy p roduced large increases in the peptide content of NPY (335 +/- 58 fmol /gland vs 15 +/- 4 fmol/gland in controls), SP (581 +/- 90 vs 199 +/- 32 fmol/gland) and VIP (1386 +/- 395 vs 417 +/- 77 fmol/gland) togethe r with large increases in the respective prohormone encoding mRNAs, NP Y 21760% +/- 1290%, preprotachykinin-A (PPT-A; which encodes the subst ance P precursor) 1744% +/- 190% and VIP 680% +/- 129%. Thyroidectomy together with T-4 replacement produced an increase in both NPY peptide (426 +/- 72 vs 15 +/- 4 fmol/gland) and mRNA content (970% +/- 156% o f controls). The peptide contents of SP and VIP were not significantly different from controls. PPT-A and VIP mRNA levels were decreased rel ative to controls (31% +/- 8% and 23% +/- 10% respectively). In intact animals treated with excess T-4 (hyperthyroid animals), SP and VIP pe ptide contents were significantly reduced (55 +/- 13 vs 199 +/- 32 fmo l/gland and 226 +/- 24 vs 417 +/- 77 fmol/gland respectively) and the SP and VIP encoding mRNAs were also decreased (8% +/- 3% and 11% +/- 4 % respectively). In this group there was no detectable alteration in e ither the peptide or mRNA content of NPY. Thus, the response of pituit ary NPY to thyroid hormone manipulations cannot be explained in terms of negative feedback physiology and is different from those of SP and VIP. The results suggest that the regulation of locally produced NPY i n the rat anterior pituitary is complex and may be influenced by thyro idal factors in addition to T-4.