Endocrinology, Vol 124, 1654-1660, Copyright © 1989 by Endocrine Society

ARTICLES

Sodium butyrate induces pyroglutamyl peptidase I and decreases thyrotropin-releasing hormone receptors in GH3 cells

CS Suen and S Wilk
Department of Pharmacology, Mount Sinai School of Medicine of the City University of New York, New York 10029.

The effect of sodium butyrate treatment on TRH-degrading enzymes and TRH receptors in GH3 cells was investigated. The specific activity of pyroglutamyl peptidase I (EC 3.4.19.3) was increased by exposure to sodium butyrate in a time- and concentration-dependent manner, whereas the specific activity of prolyl endopeptidase (EC 3.4.21.26) was unchanged. The maximal effect occurred at a concentration of 1 mM sodium butyrate and 16 h after exposure. The increase was reversible upon removal of sodium butyrate from the cell culture. Cycloheximide totally blocked the stimulation, indicating that the increase was due to new protein synthesis. Sodium butyrate had no effect on pyroglutamyl peptidase I activity in the AtT-20 cell line. [methyl-3H]TRH binding to intact GH3 cells was reduced to 70% of the control value when cells were exposed to 1 mM sodium butyrate for 8 h. A maximal decrease in binding to 40% of the control value occurred after 16 h of exposure. The Kd of [methyl-3H]TRH binding was not changed. Sodium butyrate altered GH3 cell morphology, but the morphological changes occurred after alterations of pyroglutamyl peptidase I activity and [methyl- 3H]TRH-binding sites. Other agents known to alter GH3 cell morphology had no effect on pyroglutamyl peptidase I activity. These results indicate that sodium butyrate can in some respects mimic the action of T3 on GH3 cells. Moreover, they provide further evidence that the activity of pyroglutamyl peptidase I, but not prolyl endopeptidase, is subject to regulation in the GH3 cell.