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.
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