Forskolin and thyrotrophin stimulation of rat FRTL-5 thyroid cell growth: the role of cyclic AMP

Abstract

The adenylate cyclase stimulator forskolin increases intracellular cyclic AMP (cAMP) in rat FRTL-5 cells within minutes and, after a lag phase of 20-24 h, an increase of cells in metaphase is seen. The dose-response relationships were similar in both systems, with significant increases in the number of metaphases observed at approximately 0.1 mumol/l and a doubling of cAMP levels at 1 mumol/l, whilst doses of 0.1 mmol/l and above proved cytotoxic. An involvement of intracellular cAMP as a positive intermediate in cell division was further suggested by the finding that a low dose of forskolin (0.1 mumol/l) potentiated TSH stimulation of mitosis. Isobutyl methyl xanthine (IBMX), a phosphodiesterase inhibitor, also acted as a mitogen and potentiated TSH action. Moreover, the simultaneous inclusion of low doses of IBMX and forskolin additionally potentiated TSH stimulation of mitosis. An analogue of cAMP, dibutyryl cAMP, also stimulated mitosis and acted over a restricted dose range, with maximal stimulation at 1 mmol/l. We conclude that cAMP may act as a positive signal for FRTL-5 thyroid cell proliferation.

Esta: A Bioassay System for the Determination of the Potencies of Hormones and Antibodies Which Mimic Their Action.

“…Potentiation of these responses has been observed with forskolin (not shown) which confirms that cyclic-AMP acts as a positive signal for FRTL-5 cell proliferation as observed previously (Jin, Hornicek, Neylan et al 1986;Ealey, Ahene, Emmerson & Marshall, 1987).…”

Human Chorionic Gonadotropin Promotes Thyroid Growth via Thyrotropin Receptors in FRTL-5 Cells.

“…Many studies indicate that TSH has TGA (Drexhage et al, 1980;Valente et al, 1983b;Roger and Dumont, 1984;Stringer et al, 1985;Dere and Rapoport, 1986 ;Jin et al, 1986;Ealey et al, 1987Tramontano et al, 1988Zakarija and Mckenzie, 1989), including [3H] Tdr incorporation in FRTL-5 cells as a convenient and reproducible index (Valente et al, 1983a;Jin et al, 1986;Tramontano et al, 1988;Zakarija and Mckenzie, 1989). In the present study, we showed that not only TSH but also hCG has TGA by measuring [3H] Tdr incorporation in FRTL-5 cells, which is consistent with other reports (Davies and Platzer, 1986;Hershman et al, 1988).…”

Specificity of Co-Promoting Effects of Caffeine on Thyroid Carcinogenesis in Rats Pretreated with N-Bis(2-hydroxypropyl)nitrosamine

“…Caffeine, a phosphodiesterase inhibitor, has a stimulatory effect on intracellular cAMP production, which functions as a second messenger and mediates all the intercellular effects of TSH (Kohn et al, 1985;Dumont et al, 1992). Moreover, 1-methyl-3-isobutylxanthine (IBMX), a phosphodiesterase inhibitor, also acts as a mitogen and increases TSH action (Ealey et al, 1987). However, cAMP is known to inhibit growth (Linos et al, 1989), for example of small cell lung carcinoma cell lines (Shafer et al, 1998).…”