ACTIVIN STABILIZES FOLLICLE-STIMULATING HORMONE-BETA MESSENGER-RIBONUCLEIC-ACID LEVELS

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 post-transcriptional level by increasing the stability of FSH-beta mRNA.