Inhibin, Activin, and Follistatin: Regulation of Follicle-Stimulating Hormone Messenger Ribonucleic Acid Levels

Abstract

Primary pituitary cell cultures derived from adult male rats were used to explore the direct effects of purified porcine inhibin and follistatin, and recombinant human activin A on FSHβ, as well as LHβ and α-subunit mRNA levels. Subunit mRNAs were determined by blot hybridization using α, LHβ, and FSHβ cDNA and genomic fragments. Treatment with inhibin for 72 h significantly suppressed α and FSHβ mRNA levels with parallel changes in FSH secretion. No change in LHβ mRNA levels was observed. A decrease in FSHβ mRNA to undetectable levels was seen 4 h after inhibin administration. Recombinant human Activin A caused dose-dependent and parallel increases in FSHβ mRNA levels and FSH secretion. This increase was evident at 4 h after activin administration and maintained at longer times, α and LHβ mRNA levels remained unchanged. Follistatin addition to cultures for 72 h significantly reduced FSHβ mRNA levels. In a time-course experiment, a reduction in FSHβ mRNA to undetectable levels was observed 24 h after follistatin administration. There were no changes in α or LHβ mRNA levels. These data demonstrate that the actions of these gonadal peptides on FSH secretion may be accounted for, at least in part at the level of biosynthesis, by reductions in FSHβ mRNA levels directly at the level of the anterior pituitary gland.