Transforming growth factor-α stimulates proliferation of mammotrophs and corticotrophs in the mouse pituitary

Oestrogen stimulates the proliferation of pituitary cells. The present study was designed to clarify the involvement of transforming growth factor- α (TGF-α) in the oestrogen-induced growth of mouse pituitary cells in vitro. Anterior pituitary cells obtained from ICR male mice were cultured in a primary serum-free culture system. Proliferation of pituitary cells was detected by monitoring the cellular uptake of bromodeoxyuridine. Secretory cell types were immunocytochemically determined. Treatment with TGF-α (0.1 and 1 ng/ml) for 5 days stimulated cell proliferation. Since TGF-α binds to the epidermal growth factor (EGF) receptor, this action may be exerted through the EGF receptor. Oestradiol-17β (OE₂, 10^-9 M) stimulated mammotrophic and corticotrophic cell proliferation. RG-13022, an EGF receptor inhibitor, inhibited the cell proliferation induced by EGF or OE₂, showing that the EGF receptor was involved in the growth response in mammotrophs and corticotrophs. Treatment with antisense TGF-α oligodeoxynucleotide (ODN) inhibited the cell proliferation induced by OE₂, but treatment with antisense EGF ODN did not. RT-PCR analysis revealed that OE₂ stimulated TGF- α mRNA and EGF receptor mRNA expression. These results indicate that TGF-α mediates the stimulatory effect of oestrogen on the pituitary cell proliferation in a paracrine or autocrine manner, and that EGF receptor expression is stimulated by oestrogen.