Rapid Stimulatory Effect of Activin-A on Messenger RNA Encoding the Follicle-Stimulating Hormone β-Subunit in Rat Pituitary Cell Cultures

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Abstract
Activin, a dimer of the .beta.-subunits of inhibin, stimulates FSH secretion by cultured rat pituitary cells. Both the cell content of FSH and total FSH (secreted plus intracellular) are increased by activin, suggesting an effect on FHS biosynthesis. To test this idea directly, we examined the effect of purified human activin-A of recombinant DNA origin (rhactivin-A) on steady state levels of mRNAs for the gonadotropin subunits in putuitary cell cultures prepared from adult male rats. A preliminary study of the time course of rhactivin-A action indicated that the first significant effect on FSH secretion was observed at 6 h, with maximal stimulation occurring at 24-72 h. A small (20-30%), but significant, increase in LH secretion was also observed by 24 h. For RNA analysis, putuitary cell cultures were treated for 2-72 h with a maximally effective concentration (50 ng/ml) of rhactivin-A. FSH secretion in rhactivin-A-treated cultures was elevated by 2- to 2.5-fold. Intracellular FSH increased gradually from 24-72 h. Recombinant human activin-A stimulated FSH.beta. mRNA levels at all times examined; FSH.beta. mRNA levels in activin-treated cultures were already twice those in control cultures at 2 h, and the magnitude of this effect remained constant up to 72 h. Recombinant human activin-A brought about small increases in secretion and cell content of LH and free glycoprotein .alpha.-subunit and in LH.beta. and .alpha. mRNAs at various times. Thus, the increases in gonadotropin release and cell content stimulated by rhactivin-A can be accounted for by increases in the gonadotropin subunit mRNAs. The observation that FSH.beta. mRNA levels and basal FSH secretion were elevated to the same extent by rhactivin-A suggests a close relationship between changes in FSH synthesis and release.