Effects of 17 beta-estradiol on calcitonin secretion and content in a human medullary thyroid carcinoma cell line.
The presence of a direct estrogen effect on calcitonin secretion is controversial. Because most of the data available were obtained from complex in vivo systems, we chose an in vitro approach to assess the problem. Using a human C cell carcinoma cell line (TT cells) with well-documented estrogen receptors, we investigated the effect of 17 beta-estradiol (E2) on basal and stimulated calcitonin secretion, on calcitonin content, and on total cellular protein. After short (30 and 180 minutes) and long-term (24 h to 6 days) incubation of the cells with different concentrations of E2 (from 0.01 to 100 nM) we observed no stimulatory but a transient dose-dependent inhibitory effect on CT secretion and content. The nadir of the effect on CT secretion appeared at 24 h, demonstrating a reduction to 80.5 +/- 7.8% of control at 1 nM and to 59.1 +/- 15% of control at 100 nM E2. After 72 h, the CT levels of the E2-exposed groups returned to control levels. The acute stimulation of the cells with TPA plus forskolin after preincubation with E2 up to 6 days showed no difference in the increment of CT release compared to the control groups. Additionally, E2 had a dose-dependent stimulatory effect on cell protein content. The data demonstrate the absence of a direct stimulatory effect of E2 on CT secretion, revealing a dose-dependent inhibitory effect on CT secretion and content.
Lazaretti-Castro
M
M
Department of Internal Medicine I, University of Heidelberg, FRG.
Grauer
A
A
Mekonnen
Y
Y
Raue
F
F
Ziegler
R
R
D002116:Calcitonin / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D005576:Colforsin; D004958:Estradiol; D002116:Calcitonin; D013755:Tetradecanoylphorbol Acetate