PITUITARY ACTIVIN RECEPTOR SUBTYPES AND FOLLISTATIN GENE-EXPRESSION IN FEMALE RATS - DIFFERENTIAL REGULATION BY ACTIVIN AND FOLLISTATIN

The activins, hormones produced in the gonads and extragonadal tissues (including the pituitary), rapidly increase FSH beta messenger RNA (m RNA) and FSH secretion. In the rat, activin acts via a family of activ in receptor (ActR) subunits that includes at least one type I (ActRI o r ALK-2) and two homologous type II (IIA and IIB) subunits. We have pr eviously reported that ActRIIA mRNA rises after ovariectomy (OVX). Pot entially, the OVX-induced increases in ActR mRNAs could result from al tered activin or the activin-binding protein follistatin. It was the p urpose of the current studies to determine whether activin and/or foll istatin regulated activin receptor subunit mRNAs. Adult female rat pit uitaries were dissociated and plated for 48 h, transferred to wells co ntaining follistatin or activin for 2 or 24 h, then RNA extracted for measurement of ActRI, IIA, and IIB and follistatin mRNAs. All three Ac tR mRNAs were easily detectable in pituitary RNA, with the relative ab undance of ActRI > IIA >> IIB (18:9:1). Between 2-24 h, levels of all three ActR mRNAs increased 2- to 3-fold in wells containing medium alo ne, whereas levels of follistatin mRNA were unchanged. Follistatin sig nificantly reduced FSH secretion and follistatin mRNA, but not the Act R mRNAs. Activin increased ActRI (4-fold, at 2 h), ActRIIB (2-fold, at 24 h), and follistatin (2-fold, at 24 h) mRNAs and FSH release (2-fol d, at 24 h), but did not alter ActRIIA mRNA levels. We conclude that 1 ) pituitary ActR mRNA expression is under inhibitory tone in vivo, as suggested by the effect of pituitary removal and cell dispersion and a n earlier report after OVX. 2) Pituitary-derived activin stimulates fo llistatin (but not ActR) mRNA production, and additional increases in follistatin mRNA can be induced by exogenous activin. 3) Higher concen trations of activin differentially regulate pituitary ActR mRNA expres sion, suggesting that activin exerts a positive feedback effect on its own receptor.