DECREASED FOLLISTATIN GENE-EXPRESSION IN GONADOTROPH ADENOMAS

What growth factors are involved in the pathogenesis of gonadotroph ad enomas is not yet known. Activity is one possible candidate because it stimulates growth and differentiation in many cells, including the go nadotroph cell, and it stimulates FSH secretion, characteristic of gon adotroph adenomas. As activin beta(B)-subunit is expressed in gonadotr oph adenomas, we sought to determine whether activin receptor II and f ollistatin are also expressed. Total ribonucleic acid (RNA) was extrac ted from 10 gonadotroph adenomas that did not express pit-1 and was re verse transcribed. The resulting complementary DNAs for human activin receptor II and follistatin were amplified by PCR. All 10 adenomas exp ressed activin receptor II messenger RNA (mRNA), as did nonadenomatous pituitary tissue. Only 2 of the 10 gonadotroph adenomas expressed det ectable follistatin mRNA, although all 4 nonadenomatous pituitaries di d. Quantitation of follistatin mRNA by competitive reverse transcripti on-PCR showed that none of the 10 gonadotroph adenomas expressed as mu ch follistatin mRNA as did the 4 nonadenomatous pituitaries, and 8 of the 10 expressed less than 10% as much. Immunospecific staining showed follistatin in the cytoplasm of the gonadotroph cells of all 5 nonade nomatous pituitaries studied, but only faintly in 1 gonadotroph adenom a and not at all in the other 9. These results suggest that pit-1-nega tive gonadotroph adenomas express less follistatin mRNA and follistati n peptide than do nonadenomatous gonadotroph cells. A consequence coul d be less binding, and thereby enhanced effectiveness, of activin, con tributing to adenoma growth.