Effect of antisense suppression of transforming growth factor-beta3 gene on lactotropic cell proliferation.
The mechanism by which oestrogen regulates lactotropic cell proliferation is not well understood. Recently it has been shown that a transforming growth factor beta (TGF-beta) gene-related peptide, TGF-beta3, is produced in the lactotropes and stimulates lactotropic cell proliferation in vitro. In this study, the role of this growth factor in oestrogen-induced lactotropic cell proliferation was determined in vitro using oligonucleotide designed to inhibit TGF-beta3 gene expression. We used the oligonucleotide in an antisense orientation, which is complementary to regions in the TGF-beta3 message. Oligonucleotides in sense and missense orientation were also used. We found that the antisense sequence that was effectively incorporated into pituitary cells produced a marked inhibition of the stimulatory action of oestrogen on lactotropic cell proliferation. Sense and missense oligonucleotides produced no significant effects on oestrogen-stimulated lactotropic cell proliferation. The growth-inhibitory effect of antisense oligonucleotide was blocked by TGF-beta3 peptide. These results suggest that TGF-beta3 may be involved in the processes that mediate oestrogen-regulated lactotropic cell proliferation.
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Department of Animal Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, NJ 08901, USA.
Hentges
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Boyadjieva
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Sarkar
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DK
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D019344:Lactic Acid / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053782:Transforming Growth Factor beta3
D004967:Estrogens; D016376:Oligonucleotides, Antisense; C509046:Tgfb3 protein, rat; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D019344:Lactic Acid; D011388:Prolactin