Retinoic acid and retinaldehyde dehydrogenase are not involved in the specific induction of the follicle-stimulating hormone β subunit by trichostatin A, a selective inhibitor of histone deacetylase

Abstract

The selective histone deacetylase inhibitor, trichostatin A (TSA), increases follicle-stimulating hormone β subunit (FSHβ) mRNA expression but not α- and luteinizing hormone β (LHβ)-subunits in both the pituitary gonadotrophic cell line LβT2 and primary cultures of rat anterior pituitary cells. TSA increased histone acetylation in whole cell lysates in both cells. In addition, retinaldehyde dehydrogenases (RALDHs), which are retinoic acid (RA)-synthesizing enzymes, were induced by TSA in these cells. Anacardic acid, a histone acetyltransferase inhibitor that prevents histone acetylation, significantly inhibited TSA-induced FSHβ mRNA expression as well as TSA-induced RALDH2 and RALDH3 mRNA expression. Similar to the effect of TSA, gonadotropin-releasing hormone stimulated RALDH expression in LβT2 cells. RA directly applied to the pituitary cells stimulated the transcriptional activity of the FSHβ promoter. In addition, α- and LHβ-subunit promoters were also activated by RA. Our results suggest that TSA specifically increases FSHβ expression with a concomitant increase in RALDHs; however, RALDH and RA are not directly involved in the specific regulation of FSHβ by TSA.

Keywords: Follicle-stimulating hormone; Retinaldehyde dehydrogenase; Retinoic acid; Trichostatin A.