Estrogen stimulates the proliferation of pituitary cells, in particular mammotrophs. The present study was designed to clarify involvement of transforming growth factor α (TGF-α) in the estrogen-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 a thymidine analogue, 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 this receptor. Estradiol-17β (E2, 10-9M) stimulated proliferation of mammotrophs. RG-13022, an EGF receptor inhibitor, reduced the cell proliferation induced by EGF or E2, showing that the EGF receptor was involved in this induction of mammotroph growth. Treatment with TGF-α antisense oligodeoxynucleotide (ODN) inhibited the cell proliferation induced by E2, but treatment with EGF antisense ODN did not. Dual detection of TGF-α mRNA and growth hormone by in situ hybridization and fluorescenceimmunocytochemistry demonstrated that TGF-α mRNA was detected in most somatotrophs. Our recent RT-PCR analysis revealed that E2 stimulated TGF-α-mRNA and EGF-receptor mRNA expression. These results indicate that TGF-α produced in somatotrophs mediates the stimulatory effect of estrogen on pituitary cell proliferation in a paracrine manner, and that EGF-receptor expression is stimulated by estrogen. These findings indicate that intrapituitary cell-to-cell interaction plays an important role in the control of pituitary secretory cells.
ASJC Scopus subject areas
- Physiology (medical)