Activin Stabilizes Follicle-Stimulating Hormone-Beta Messenger Ribonucleic Acid Levels

Abstract

Activin, a gonadal peptide, stimulates FSH secretion in association with an increase in FSH beta messenger RNA (mRNA) levels at the level of the anterior pituitary gland. The goal of these studies was to determine whether the effects of recombinant human activin A (rhActivin A) are exerted at the post-transcriptional level by affecting the stability of FSH beta mRNA. We determined the apparent half-life of FSH beta mRNA in the presence and absence of rhActivin A using actinomycin D. The anterior pituitary glands from adult male rats were isolated and dispersed enzymatically. Cells were preincubated in the presence of rhActivin A for 24 h to increase FSH beta mRNA levels. Actinomycin D was then added and the cells were incubated for a subsequent 4, 6, 8, 12, and 24 h in the presence or absence of rhActivin A. As reported earlier, the addition of rhActivin A caused parallel increases in FSH secretion and FSH beta mRNA levels, while having no effect on alpha or LH beta mRNA levels. Actinomycin D treatment decreased FSH beta mRNA to 49, 39, and 16% of control levels at the 4, 6, and 8 h time points, respectively. In contrast, when actinomycin D was added in the presence of rhActivin A FSH beta mRNA was reduced to 80, 58, and 42% of control levels at the 4, 6, and 8 h time points, respectively. Using the least squares method of analysis, the apparent half-lives of FSH beta mRNA under these two conditions were calculated. In the presence of actinomycin D, the half-life of FSH beta mRNA was 3.1 h. The addition of activin significantly increased the half-life to 6.5 h. These results suggest that activin A stimulates FSH beta mRNA levels, at least in part, at the posttranscriptional level by increasing the stability of FSH beta mRNA.