title: Intrapituitary regulatory system of mammotrophs in the mouse.
abstract: Estrogen stimulates the proliferation of pituitary cells, in particular mammotrophs. The present study was designed to clarify involvement of transforming growth factor alpha (TGF-alpha) 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-alpha (0.1 and 1 ng/ml) for 5 days stimulated cell proliferation. Since TGF-alpha binds to the epidermal growth factor (EGF)-receptor, this action may be exerted through this receptor. Estradiol-17beta (E2, 10(-9) M) 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-alpha antisense oligodeoxynucleotide (ODN) inhibited the cell proliferation induced by E2, but treatment with EGF antisense ODN did not. Dual detection of TGF-alpha mRNA and growth hormone by in situ hybridization and fluorescence-immunocytochemistry demonstrated that TGF-alpha mRNA was detected in most somatotrophs. Our recent RT-PCR analysis revealed that E2 stimulated TGF-alpha-mRNA and EGF-receptor mRNA expression. These results indicate that TGF-alpha 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.
authors.affiliation: Department of Biology, Faculty of Science, Okayama University, Tsushima, Japan. stakaha@cc.okayama-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.forename: S
authors.initials: S
authors.lastname: Oomizu
authors.forename: J
authors.initials: J
authors.lastname: Honda
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004261:DNA Replication / Q000502:physiology; D004815:Epidermal Growth Factor / Q000235:genetics / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000502:physiology*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D020319:Oligodeoxyribonucleotides, Antisense; D016211:Transforming Growth Factor alpha; D020032:Tyrphostins; C070274:RG 13022; D004815:Epidermal Growth Factor; D066246:ErbB Receptors