cyclic AMP; thyroid; thyrotropin; protein kinase A; mitogenic; cell proliferation; function; differentiation; human
Abstract :
[en] Cyclic AMP has been shown to inhibit cell proliferation in many cell types and to activate it in some. The latter has been recognized only lately, thanks in large part to studies on the regulation of thyroid cell proliferation in dog thyroid cells. The steps that led to this conclusion are outlined. Thyrotropin activates cyclic accumulation in thyroid cells of all the studied species and also phospholipase C in human cells. It activates directly cell proliferation in rat cell lines, dog, and human thyroid cells but not in bovine or pig cells. The action of cyclic AMP is responsible for the proliferative effect of TSH. It accounts for several human diseases: congenital hyperthyroidism, autonomous adenomas, and Graves' disease; and, by default, for hypothyroidism by TSH receptor defect. Cyclic AMP proliferative action requires the activation of protein kinase A, but this effect is not sufficient to explain it. Cyclic AMP action also requires the permissive effect of IGF-1 or insulin through their receptors, mostly as a consequence of PI3 kinase activation. The mechanism of these effects at the level of cyclin and cyclin-dependent protein kinases involves an induction of cyclin D3 by IGF-1 and the cyclic AMP-elicited generation and activation of the cyclin D3-CDK4 complex
Pastan, I., Johnson, G.S., Cyclic AMP and the transformation of fibroblasts (1974) Adv. Cancer Res., 19, pp. 303-329
Boynton, A.L., Whitfield, J.F., Kleine, L.P., Ca2+/phospholipid-dependent protein kinase activity correlates to the ability of transformed liver cells to proliferate in Ca2+-deficient medium (1983) Biochem. Biophys. Res. Commun., 115, pp. 383-390
Pastan, I., Katzen, R., Activation of adenyl cyclase in thyroid homogenates by thyroid-stimulating hormone (1967) Biochem. Biophys. Res. Commun., 26, pp. 792-798
Gilman, A.G., Rall, T.W., The role of adenosine 3′,5′-phosphate in mediating effects of thyroid-stimulating hormone on carbohydrate metabolism of bovine thyroid slices (1968) J. Biol. Chem., 243, pp. 5872-5881
Gilman, A.G., Rall, T.W., Factors influencing adenosine 3′,5′-phosphate accumulation in bovine thyroid slices (1968) J. Biol. Chem., 243, pp. 5867-5871
Rodesch, F., Neve, P., Willems, C., Stimulation of thyroid metabolism by thyrotropin, cyclic 3′,5′ AMP dibutyryl cyclic 3′,5′ AMP and prostaglandin E1 (1969) Eur. J. Biochem., 8, pp. 26-32
Dumont, J.E., Willems, C., Van Sande, J., Regulation of the release of thyroid hormones: Role of cyclic AMP (1971) Ann. N.Y. Acad. Sci., 185, pp. 291-316
Dumont, J.E., The action of thyrotropin on thyroid metabolism (1971) Vitam. Horm., 29, pp. 287-412
Laurent, E., Mockel, J., Van Sande, J., Dual activation by thyrotropin of the phospholipase C and cAMP cascades in human thyroid (1987) Mol. Cell. Endocrinol., 52, pp. 273-278
Westermark, B., Karlsson, F.A., Walinder, O., Thyrotropin is not a growth factor for human thyroid cells in culture (1979) Proc. Natl. Acad. Sci. USA, 76, pp. 2022-2026
Gärtner, R., Greil, W., Demharter, P., Involvement of cyclic AMP, iodine and metabolites of arachidonic acid in the regulation of cell proliferation of isolated porcine thyroid follicles (1985) Mol. Cell. Endocrinol., 42, pp. 145-155
Eggo, M.C., Bachrach, L.R., Fayet, G., The effects of growth factors and serum on DNA synthesis and differentiation in thyroid cells in culture (1984) Mol. Cell. Endocrinol., 38, pp. 141-150
Errick, J.E., Ing, K.W.A., Eggo, M.C., Growth and differentiation in cultured human thyroid cells: Effects of epidermal growth factor and thyrotropin (1986) In Vitro, 22, pp. 28-36
Roger, P.P., Hotimsky, A., Moreau, C., Stimulation by thyrotropin, cholera toxin and dibutyryl cyclic AMP of the multiplication of differentiated thyroid cells in vitro (1982) Mol. Cell. Endocrinol., 26, pp. 165-172
Roger, P.D., Servais, P., Dumont, J.E., Stimulation by thyrotropin and cyclic AMP of the proliferation of quiescent canine thyroid cells cultured in a defined medium containing insulin (1983) FEBS Lett., 157, pp. 323-329
Kerkof, P.R., Long, P.J., Chaikoff, I.L., In vitro effects of thyrotropin hormone. I. On the pattern of organization of monolayer cultures of isolated sheep thyroid gland (1964) Endocrinology, 74, pp. 170-179
Fayet, G., Michel-Bechet, M., Lissitzky, S., Thyrotropin-induced aggregation and reorganization into follicles of isolated porcine thyroid cells in culture (1971) Eur. J. Biochem., 24, pp. 100-111
Rapoport, B., Dog thyroid cells in monolayer tissue culture: Adenosine 3′-5′-cyclic monophosphate response to thyrotropic hormone (1976) Endocrinology, 98, pp. 1189-1197
Baptist, M., Dumont, J.E., Roger, P.P., Demonstration of cell cycle kinetics in thyroid primary culture by immunostaining of proliferating cell nuclear antigen: Differences in cyclic AMP-dependent and -independent mitogenic stimulations (1993) J. Cell Sci., 105, pp. 69-80
Roger, P.P., Dumont, J.E., Factors controlling proliferation and differentiation of canine thyroid cells cultured in reduced serum conditions: Effects of thyrotropin, cyclic AMP and growth factors (1984) Mol. Cell. Endocrinol., 36, pp. 79-93
Ambesi-Impiombato, F.S., Parks, L.A.M., Coon, H.G., Culture of hormone-dependent functional epithelial cells froml rat thyroids (1980) Proc. Natl. Acad. Sci. USA, 77, pp. 3455-3459
Valente, W.A., Vitti, P., Kohn, L.D., The relationship of growth and adenylate cyclase activity in cultured thyroid cells. Separate bioeffects of thyrotropin (1983) Endocrinology, 112, pp. 71-79
Dere, W.H., Rapoport, B., Control of growth in cultured rat thyroid cells (1986) Mol. Cell. Endocrinol., 44, pp. 195-199
Jin, S., Hornicek, F.J., Neylan, D., Evidence that adenosine 3′,5′-monophosphate mediates stimulation of thyroid growth in FRTL-5 cells (1986) Endocrinology, 119, pp. 802-810
Tramontano, D., Moses, A.C., Ingbar, S.H., The role of adenosine 3′,5′-monophosphate in the regulation of receptors for thyrotropin and insulin-like growth factor I in the FRTL-5 rat thyroid follicular cell (1988) Endocrinology, 122, pp. 133-136
Tramontano, D., Moses, A.C., Veneziani, B.M., Adenosine 3′,5′-monophosphate mediates both the mitogenic effect of thyrotropin and its ability to amplify the response to insulin-like growth factor I in FRTL-5 cells (1988) Endocrinology, 122, pp. 127-132
Allgeier, A., Laugwitz, K.L., Van Sande, J., Multiple G-protein coupling of the dog thyrotropin receptor (1997) Mol. Cell. Endocrinol., 127, pp. 81-90
Roger, P.P., Dumont, J.E., Epidermal growth factor controls the proliferation and the expression of differentiation in canine thyroid cells in primary culture (1982) FEBS Lett., 144, pp. 209-212
Dremier, S., Taton, M., Coulonval, K., Mitogenic, dedifferentiating, and scattering effects of hepatocyte growth factor on dog thyroid cells (1994) Endocrinology, 135, pp. 135-140
Roger, P.P., Reuse, S., Servais, P., Stimulation of cell proliferation and inhibition of differentiation expression by tumor-promoting phorbol esters in dog thyroid cells in primary culture (1986) Cancer Res., 46, pp. 898-906
Roger, P.P., Servais, P., Dumont, J.E., Induction of DNA synthesis in dog thyrocytes in primary culture: Synergistic effects of thyrotropin and cyclic AMP with epidermal growth factor and insulin (1987) J. Cell. Physiol., 130, pp. 58-67
Burikhanov, R., Coulonval, K., Pirson, I., Thyrotropin via cyclic AMP induces insulin receptor expression and insulin co-stimulation of growth and amplifies insulin and insulin-like growth factor signaling pathways in dog thyroid epithelial cells (1996) J. Biol. Chem., 271, pp. 29400-29406
Deleu, S., Pirson, I., Clermont, F., Immediate early gene expression in dog thyrocytes in response to growth, proliferation, and differentiation stimuli (1999) J. Cell. Physiol., 181, pp. 342-354
Roger, P.P., Van Heuverswyn, B., Lambert, C., Antagonistic effects of thyrotropin and epidermal growth factor on thyroglobulin mRNA level in cultured thyroid cells (1985) Eur. J. Biochem., 152, pp. 239-245
Pohl, V., Roger, P.P., Christophe, D., Differentiation expression during proliferative activity induced through different pathways: In situ hybridization study of thyroglobulin gene expression in thyroid epithelial cells (1990) J. Cell Biol., 111, pp. 663-672
Gérard, C., Lefort, A., Christophe, D., Control of thyroperoxidase and thyroglobulin transcription by cAMP: Evidence for distinct regulatory mechanisms (1989) Mol. Endocrinol., 3, pp. 2110-2118
De Deken, X., Wang, D., Many, M.C., Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family (2000) J. Biol. Chem., 275, pp. 23227-23233
Roger, P.P., Taton, M., Van Sande, J., Mitogenic effects of thyrotropin and adenosine 3′,5′-monophosphate in differentiated normal human thyroid cells in vitro (1988) J. Clin. Endocrinol. Metab., 66, pp. 1158-1165
Lamy, F., Taton, M., Dumont, J.E., Control of protein synthesis by thyrotropin and epidermal growth factor in human thyrocytes: Role of morphological changes (1990) Mol. Cell. Endocrinol., 73, pp. 195-209
Maenhaut, C., Brabant, G., Vassart, G., In vitro and in vivo regulation of thyrotropin receptor mRNA levels in dog and human thyroid cells (1992) J. Biol. Chem., 267, pp. 3000-3007
Dumont, J.E., Jauniaux, J.C., Roger, P.P., The cyclic AMP-mediated stimulation of cell proliferation (1989) Trends Biochem. Sci., 14, pp. 67-71
Libert, F., Parmentier, M., Lefort, A., Selective amplification and cloning of four new members of the G protein-coupled receptor family (1989) Science, 244, pp. 569-572
Maenhaut, C., Van Sande, J., Libert, F., RDC8 codes for an adenosine A2 receptor with physiological constitutive activity (1990) Biochem. Biophys. Res. Commun., 173, pp. 1169-1178
Ledent, C., Dumont, J.E., Vassart, G., Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism (1991) EMBO J., 11, pp. 537-542
Michiels, F.M., Caillou, B., Talbot, M., Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice (1994) Proc. Natl. Acad. Sci. USA, 91, pp. 10488-10492
Zeiger, M.A., Saji, M., Gusev, Y., Thyroid-specific expression of cholera toxin A1 subunit causes thyroid hyperplasia and hyperthyroidism in transgenic mice (1997) Endocrinology, 138, pp. 3133-3140
Kjelsberg, M.A., Cotecchia, S., Ostrowski, J., Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation (1992) J. Biol. Chem., 267, pp. 1430-1433
Parmentier, M., Libert, F., Maenhaut, C., Molecular cloning of the thyrotropin (TSH) receptor (1989) Science, 296, pp. 1620-1622
Parmentier, M., Libert, F., Maenhaut, C., Nucleotide sequence of the dog thyrotropin receptor cDNA (1989) Nucleic Acids Res., 17, pp. 10493-10494
Parma, J., Duprez, L., Van Sande, J., Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas (1993) Nature, 365, pp. 649-651
Parma, J., Van Sande, J., Swillens, S., Somatic mutations causing constitutive activity of the thyrotropin receptor are the major cause of hyperfunctioning thyroid adenomas: Identification of additional mutations activating both the cyclic adenosine 3′,5′-monophosphate and inositol phosphate-Ca2+ cascades (1995) Mol. Endocrinol., 9, pp. 725-733
Dremier, S., Pohl, V., Poteet-Smith, C., Activation of cyclic AMP-dependent kinase is required but may not be sufficient to mimic cyclic AMP-dependent DNA synthesis and thyroglobulin expression in dog thyroid cells (1997) Mol. Cell. Biol., 17, pp. 6717-6726
Duprez, L., Parma, J., Costagliola, S., Constitutive activation of the TSH receptor by spontaneous mutations affecting the N-terminal extracellular domain (1997) FEBS Lett., 409, pp. 469-474
Duprez, L., Parma, J., Van Sande, J., Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism (1994) Nat. Genet., 7, pp. 396-401
Abramowicz, M.J., Duprez, L., Parma, J., Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland (1997) J. Clin. Invest., 99, pp. 3018-3024
Weinstein, L.S., Shenker, A., Gejman, P.V., Activating mutations of the stimulatory G protein in the McCune-Albright syndrome (1991) N. Engl. J. Med., 325, pp. 1688-1695
Mastorakos, G., Mitsiades, N.S., Doufas, A.G., Hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty years after the first report (1997) Thyroid, 7, pp. 433-439
Gupta, M.K., Thyrotropin-receptor antibodies in thyroid diseases: Advances in detection techniques and clinical applications (2000) Clin. Chim. Acta, 293, pp. 1-29
Roger, P.P., Reuse, S., Maenhaut, C., Multiple facets of the modulation of growth by cAMP (1995) Vitam. Horm., 51, pp. 59-191
Richards, J.S., New signaling pathways for hormones and cyclic adenosine 3′,5′-monophosphate action in endocrine cells (2001) Mol. Endocrinol., 15, pp. 209-218
Roger, P.P., Baptist, M., Dumont, J.E., A mechanism generating heterogeneity in thyroid epithelial cells: Suppression of the thyrotropin/cAMP-dependent mitogenic pathway after cell division induced by cAMP-independent factors (1992) J. Cell Biol., 117, pp. 383-393
Kimura, T., Van Keymeulen, A., Golstein, J., Regulation of thyroid cell proliferation by tsh and other factors: A critical evaluation of in vitro models (2001) Endocr. Rev., 22, pp. 631-656
Lamy, F., Wilkin, F., Baptist, M., Phosphorylation of mitogen-activated protein kinases is involved in the epidermal growth factor and phorbol ester, but not in the thyrotropin/cAMP, thyroid mitogenic pathways (1993) J. Biol. Chem., 268, pp. 8398-8401
Van Keymeulen, A., Roger, P.P., Dumont, J.E., TSH and cAMP do not signal mitogenesis through Ras activation (2000) Biochem. Biophys. Res. Commun., 273, pp. 154-158
Coulonval, K., Vandeput, F., Stein, R.C., Phosphatidylinositol 3-kinase, protein kinase B and ribosomal S6 kinases in the stimulation of thyroid epithelial cell proliferation by cAMP and growth factors in the presence of insulin (2000) Biochem. J., 348 (PART 2), pp. 351-358
Eccles, N., Ivan, M., Wynford-Thomas, D., Mitogenic stimulation of normal and oncogene-transformed human thyroid epithelial cells by hepatocyte growth factor (1996) Mol. Cell. Endocrinol., 117, pp. 247-251
Saunier, B., Tournier, C., Jacquemin, C., Stimulation of mitogen-activated protein kinase by thyrotropin in primary cultured human thyroid follicles (1995) J. Biol. Chem., 270, pp. 3693-3697
Contor, L., Lamy, F., Lecocq, R., Differential protein phosphorylation in induction of thyroid cell proliferation by thyrotropin, epidermal growth factor, or phorbol ester (1988) Mol. Cell. Biol., 8, pp. 2494-2503
Van Sande, J., Lefort, A., Beebe, S., Pairs of cyclic AMP analogs, that are specifically synergistic for type I and type II cAMP-dependent protein kinases, mimic thyrotropin effects on the function, differentiation expression and mitogenesis of dog thyroid cells (1989) Eur. J. Biochem., 183, pp. 699-708
Uyttersprot, N., Costagliola, S., Dumont, J.E., Requirement for cAMP-response element (CRE) binding protein/CRE modulator transcription factors in thyrotropin-induced proliferation of dog thyroid cells in primary culture (1999) Eur. J. Biochem., 259, pp. 370-378
De Rooij, J., Zwartkruis, F.J., Verheijen, M.H., Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP (1998) Nature, 396, pp. 474-477
Dumont, J.E., Lamy, F., Roger, P.P., Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors (1992) Physiol. Rev., 72, pp. 667-697
Clément, S., Refetoff, S., Robaye, B., Low TSH requirement and goiter in transgenic mice overexpressing IGF-I and IGF-I receptor in the thyroid gland (2001) Endocrinology, 142, pp. 5131-5139
Cheung, N.W., Lou, J.C., Boyages, S.C., Growth hormone does not increase thyroid size in the absence of thyrotropin: A study in adults with hypopituitarism (1996) J. Clin. Endocrinol. Metab., 81, pp. 1179-1183
Van Keymeulen, A., Dumont, J.E., Roger, P.P., TSH induces insulin receptors that mediate insulin costimulation of growth in normal thyroid cells (2000) Biochem. Biophys. Res. Commun., 279, pp. 202-207
Van Keymeulen, A., Deleu, S., Bartek, J., Respective roles of carbamylcholine and cyclic adenosine monophosphate in their synergistic regulation of cell cycle in thyroid primary cultures (2001) Endocrinology, 142, pp. 1251-1259
Reuse, S., Maenhaut, C., Dumont, J.E., Regulation of protooncogenes c-fos and c-myc expressions by protein tyrosine kinase, protein kinase C, and cyclic AMP mitogenic pathways in dog primary thyrocytes: A positive and negative control by cyclic AMP on c-myc expression (1990) Exp. Cell Res., 189, pp. 33-40
Reuse, S., Pirson, I., Dumont, J.E., Differential regulation of protooncogenes c-jun and jun D expressions by protein tyrosine kinase, protein kinase C, and cyclic-AMP mitogenic pathways in dog primary thyrocytes: TSH and cyclic-AMP induce proliferation but downregulate C-jun expression (1991) Exp. Cell Res., 196, pp. 210-215
Deleu, S., Pirson, I., Coulonval, K., IGF-1 or insulin, and the TSH cyclic AMP cascade separately control dog and human thyroid cell growth and DNA synthesis, and complement each other in inducing mitogenesis (1999) Mol. Cell. Endocrinol., 149, pp. 41-51
Pirson, I., Coulonval, K., Lamy, F., C-myc expression is controlled by the mitogenic cAMP-cascade in thyrocytes (1996) J. Cell. Physiol., 168, pp. 59-70
Coulonval, K., Maenhaut, C., Dumont, J.E., Phosphorylation of the three Rb protein family members is a common step of the cAMP-, the growth factor, and the phorbol ester-mitogenic cascades but is not necessary for the hypertrophy induced by insulin (1997) Exp. Cell Res., 233, pp. 395-398
Depoortere, F., Van Keymeulen, A., Lukas, J., A requirement for cyclin D3-cyclin-dependent kinase (cdk)-4 assembly in the cyclic adenosine monophosphate-dependent proliferation of thyrocytes (1998) J. Cell Biol., 140, pp. 1427-1439
Coppée, F., Depoortere, F., Bartek, J., Differential patterns of cell cycle regulatory proteins expression in transgenic models of thyroid tumours (1998) Oncogene, 17, pp. 631-641
Van Keymeulen, A., Bartek, J., Dumont, J.E., Cyclin D3 accumulation and activity integrate and rank the comitogenic pathways of thyrotropin and insulin in thyrocytes in primary culture (1999) Oncogene, 18, pp. 7351-7359
Depoortere, F., Pirson, I., Bartek, J., Transforming growth factor β1 selectively inhibits the cyclic AMP-dependent proliferation of primary thyroid epithelial cells by preventing the association of cyclin D3-cdk4 with nuclear p27kip1 (2000) Mol. Cell. Biol., 11, pp. 1061-1076
Pirson, I., Fortemaison, N., Jacobs, C., The visual display of regulatory information and networks (2000) Trends Cell Biol., 10, pp. 404-408
Staples, K.J., Bergmann, M., Tomita, K., Adenosine 3′,5′-cyclic monophosphate (cAMP)-dependent inhibition of IL-5 from human T lymphocytes is not mediated by the cAMP-dependent protein kinase A (2001) J. Immunol., 167 (4), pp. 2074-2080
Wang, L., Liu, F., Adamo, M.L., Cyclic AMP inhibits extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways by inhibiting Rap 1 (2001) J. Biol. Chem., 276 (40), pp. 37242-37249
