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Division of Genetics, Department of Medicine (R.S.C., W.W.C.), Brigham and Women's Hospital; Howard Hughes Medical Institute and Harvard Medical School Boston, Massachusetts 02115
Clayton Foundation Laboratories for Peptide Biology (A.Z.C., W. V.), The Salk Institute La Jolla, California 92037
Address all correspondence and requests for reprints to: Dr. Rona Carroll, G. W. Thorn Research Building, Room 905, Brigham and Womens Hospital, 20 Shattuck Street, Boston, Massachusetts 02115.
Abstract
Activin, a gonadal peptide, stimulates FSH secretion in association with an increase in FSHfβ 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 FSHβ mRNA. We determined the apparent half-life of FSHβ 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 FSHβ 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 FSHβ mRNA levels, while having no effect on a or LHβ mRNA levels, Actinomycin D treatment decreased FSHβ 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 FSHβ 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 FSHβ mRNA under these two conditions were calculated. In the presence of actinomycin D, the half-life of FSHβ 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 FSHβ mRNA levels, at least in part, at the posttranscription a I level by increasing the stability of FSHβ mRNA. (Endocrinology 129: 1721–1726, 1991)
Received September 4, 1991.
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