Transforming growth factor-beta, but not ciliary neurotrophic factor, inhibits DNA synthesis of adrenal medullary cells in vitro.
Transforming growth factor-betas are members of a superfamily of multifunctional cytokines regulating cell growth and differentiation. Their functions in neural and endocrine cells are not well understood. We show here that transforming growth factor-betas are synthesized, stored and released by the neuroendocrine chromaffin cells, which also express the transforming growth factor-beta receptor type II. In contrast to the developmentally related sympathetic neurons, chromaffin cells continue to proliferate throughout postnatal life. Using 5-bromo-2'-deoxyuridine pulse labeling and tyrosine hydroxylase immunocytochemistry as a marker for young postnatal rat chromaffin cells, we show that treatment with fibroblast growth factor-2 (1 nM) and insulin-like growth factor-II (10 nM) increased the fraction of 5-bromo-2'-deoxyuridine-labeled nuclei from 1% to about 40% of the cells in the absence of serum. In the presence of fibroblast growth factor-2 and insulin-like growth factor-II, transforming growth factor-beta1 (0.08 nM) reduced 5-bromo-2'-deoxyuridine labeling by about 50%, without interfering with chromaffin cell survival or death. Doses lower and higher than 0.08 nM were less effective. Similar effects were seen with transforming growth factor-beta3. In contrast to transforming growth factor-beta, ciliary neurotrophic factor, which inhibits proliferation of sympathetic progenitor cells, was not effective on rat chromaffin cells from postnatal day 6. Glucocorticoids also suppress DNA synthesis in fibroblast growth factor-2/insulin-like growth factor-II-treated chromaffin cells. This effect was not mediated by chromaffin cell-derived transforming growth factor-beta, as shown by addition of neutralizing antibodies. We conclude that one function of adrenal medullary transforming growth factor-beta may be to act as a negative regulator of chromaffin cell division.
Wolf
N
N
Department of Neuroanatomy, The University of Heidelberg, Germany.
Krohn
K
K
Bieger
S
S
Frödin
M
M
Gammeltoft
S
S
Krieglstein
K
K
Unsicker
K
K
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D004247:DNA / Q000096:biosynthesis*; D017931:DNA Primers; D004261:DNA Replication / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017208:Rats, Wistar; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; D017931:DNA Primers; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D007335:Insulin-Like Growth Factor II; D002217:Carbachol; D004247:DNA; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II