Effect of antisense suppression of transforming growth factor-beta3 gene on lactotropic cell proliferation

The mechanism by which oestrogen regulates lactotropic cell proliferation is not well understood. Recently it has been shown that a transforming growth factor beta (TGF-beta) gene-related peptide, TGF-beta3, is produced in the lactotropes and stimulates lactotropic cell proliferation in vitro. In this study, the role of this growth factor in oestrogen-induced lactotropic cell proliferation was determined in vitro using oligonucleotide designed to inhibit TGF-beta3 gene expression. We used the oligonucleotide in an antisense orientation, which is complementary to regions in the TGF-beta3 message. Oligonucleotides in sense and missense orientation were also used. We found that the antisense sequence that was effectively incorporated into pituitary cells produced a marked inhibition of the stimulatory action of oestrogen on lactotropic cell proliferation. Sense and missense oligonucleotides produced no significant effects on oestrogen-stimulated lactotropic cell proliferation. The growth-inhibitory effect of antisense oligonucleotide was blocked by TGF-beta3 peptide. These results suggest that TGF-beta3 may be involved in the processes that mediate oestrogen-regulated lactotropic cell proliferation.