Possible involvement of transforming growth factor-beta in the inhibition of rat pituitary tumor growth by estradiol.
We have shown that growth of F4Z2 cells and F4Z2 tumors was stimulated by estradiol, that of MtTF4 and F4P tumors was inhibited and that of F4P cells remained insensitive. In the present work we explore the possible role of transforming growth factor-beta (TGF-beta) as a mediator of estradiol action in these pituitary tumors and cell lines. In vivo, estradiol treatment increased the concentration of TGF-beta 1 mRNAs in tumors whose growth was inhibited by estradiol (MtTF4 and F4P) but not in tumors whose growth was stimulated (F4Z2). F4Z2 and F4P cell lines also contained TGF-beta 1 transcripts. These cells and tumors differed by two points: the level of TGF-beta 1 transcript was higher in F4Z2 than in F4P cells while the opposite situation was observed in vivo and the concentration of TGF-beta 1 mRNA in cultured cells was insensitive to estradiol (1 or 100 x 10(-9) M). Moreover, the secretion of TGF-beta like activity assayed by two different methods was estradiol insensitive and the growth of both cell lines was dose-dependently inhibited by TGF-beta 1 (ED50:2 x 10(-11) M). Since estradiol increases TGF-beta 1 mRNA in the tumors MtTF4 and F4P whose growth is inhibited by estradiol and that TGF-beta 1 inhibits the proliferation of F4P cells it is proposed as a working hypothesis that TGF-beta 1 is one of the mediators of the inhibitory effect of estradiol in pituitary tumors. No data favor the hypothesis that estradiol stimulates pituitary tumor proliferation by decreasing TGF-beta production.
Albaladejo
V
V
INSERM-U.329, Hôpital Debrousse, Lyon, France.
Feï
Z L
ZL
Nicolas
B
B
Joly-Pharaboz
M O
MO
Avallet
O
O
Vigier
M
M
André
J
J
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000502:physiology*; D005260:Female; D010911:Pituitary Neoplasms / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016212:Transforming Growth Factor beta; D004958:Estradiol