Summary
The cyclic adenosine monophosphate (cAMP) generator choleratoxin is known to promote the growth of sebaceous epithelial cells (sebocytes) in monolayer culture in classical serum-containing media. Now that sebocytes can be grown in serum-free medium, we have examined whether choleratoxin or other cAMP generators are required for differentiation of rat preputial sebocytes in response to specific ligand activators of peroxisome proliferator-activated receptors (PPARs). Unexpectedly, choleratoxin reduced sebocyte proliferation. However, sebocyte differentiation in response to specific PPAR-α and PPARγ agonists required a cAMP generator such as choleratoxin, and this response was suppressed by a protein kinase A inhibitor. In contrast, the stable prostacyclin analog, carbaprostacyclin (cPGI2), a PPARα,δ agonist that also generates cAMP, stimulated differentiation independently of choleratoxin. Furthermore, unlike the selective PPARα and PPARγ agonists, cPGI2 stimulated both sebocyte DNA synthesis and proliferation. These data are compatible with the evidence that prostacyclin has the additional effect of generating cAMP. In addition, we addressed the possibility that choleratoxin may act as a surrogate for β-adrenergic catecholamines in generating cAMP. In contrast with choleratoxin, both α- and β-adrenergic catecholamines stimulated sebocyte growth and interfered with the choleratoxin effect on differentiation. These data suggest ligand-dependent, complex interactions between cAMP and the other signal transduction pathways involved in sebocyte growth and development.
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Altiok, S.; Xu, M.; Spiegelman, B. M. PPARgamma induces cell cycle with-drawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev. 11:1987–1998; 1997.
Andersen, A.; Pedersen, H.; Bendtzen, K.; Ropke, C. Effects of growth factors on cytokine production in serum-free cultures of human thymic epithelial cells. Scand. J. Immunol. 38:233–238; 1993.
Berger, J.; Leibowitz, M. D.; Doebber, T. W., et al. Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J. Biol. Chem. 274:6718–6725; 1999.
Brun, R.; Tontonoz, P.; Forman, B.; Ellis, R.; Chen, J.; Evans, R.: Spiegelman, B. Differential activation of adipogenesis by multiple PPAR isoforms. Genes Dev. 10:974–984; 1996.
Daaka, Y.; Luttrell, L. M.; Lefkowitz, R. J. Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A. Nature 390;88–91; 1997.
Deplewski, D.; Rosenfield, R. L. Growth hormone and insulin-like growth factors have different effects on sebaceous cell growth and differentiation. Endocrinology 140;4089–4094; 1999.
de Wit, R. J.; Hekstra, D.; Jastorff, B.; Stec, W. J.; Baraniak, J.; Van Driel, R.; Van Haastert, P. J. Inhibitory action of certain cyclophosphate derivatives of cAMP on cAMP-dependent protein kinases. Eur. J. Biochem. 142:255–260; 1984.
Ellis, C. N.; Varani, J.; Fisher, G. J.; Zeigler, M. E.; Pershadsingh, H. A.; Benson, S. C.; Chi, Y.; Kurtz, T. W. Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-gamma inhibit keratinocyte proliferation. Arch Dermatol. 136:609–616; 2000.
Field, M.; Rao, M. C.; Chang, E. B. Intestinal electrolyte transport and diarrheal disease (2). N. Engl. J. Med. 321:879–883; 1989.
Hanley, K.; Jiang, Y.; He, S. S.; Friedman, M.; Elias, P. M.; Bikle, D. D.; Williams, M. L.; Feingold, K. R.: Neratinocyte differentiation is stimulated by activators of the nuclear hormone receptor PPARalpha. J. Invest. Dermatol. 110;368–375; 1998.
Hansen, J. B.; Zhang, H.; Rasmussen, T. H.; Petersen, R. K.; Flindt, E. N.; Kristiansen, K. Peroxisome proliferator-activated receptor δ-mediated regulation of preadipocyte proliferation and gene expression is dependent on cAMP signaling. J. Biol. Chem. 276;3175–3182; 2001.
Kim, M. J.; Ciletti, N.; Michel, S.; Reichert, U.; Rosenfield, R. L. The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J. Invest. Dermatol. 114:349–353; 2000.
Laurent, S. J.; Mednieks, M. I.; Rosenfield, R. L. Growth of sebaceous cells in monolayer culture. In Vitro Cell. Dev. Biol. 28A:83–89; 1992.
Lazennec, G.; Canaple, L.; Saugy, D.; Wahli, W. Activation of peroxisome proliferator-activated receptors (PPARs) by their ligands and protein kinase A activators. Mol. Endocrinol. 14:1962–1975; 2000.
Lefkowitz, R. J.; Hoffman, B. B.; Taylor, P. Neurohumoral transmission: the autonomic and somatic motor nervous systems. In: Gilman, A. G.; Rall, T. W.; Nies, A. S.; Taylor, P., ed. The pharmacological basis of therapeutics. New York: Pergamon Press; 1990:84–121.
Mednieks, M. I.; Laurent, S. J.; Hand, A. R.; Rosenfield, R. L. Cyclic AMP-receptor protein activity in rat preputial cells. J. Invest. Dermatol. 97:517–523; 1991.
Peters, J. M.; Aoyama, T.; Cattley, R. C.; Nobumitsu, U.; Hashimoto, T.; Gonzalez, F. J. Role of peroxisome proliferator-activated receptor alpha in altered cell cycle regulation in mouse liver. Carcinogenesis 19:1989–1994; 1998.
Richards, J. S. New signaling pathways for hormones and cyclic adenosine 3′,5′-monophosphate action in endocrine cells. Mol. Endocrinol. 15:209–218; 2001.
Rosenfield, R. L.; Deplewski, D.; Kentsis, A.; Ciletti, N. Mechanisms of androgen induction of sebocyte differentiation. Dermatology 196:43–46; 1998.
Rosenfield, R. L.; Kentsis, A.; Deplewski, D.; Ciletti, N. Rat preputial sebocyte differentiation involves peroxisome proliferator-activated receptors. J. Invest. Dermatol. 112:226–232; 1999.
Vassaux, G.; Gaillard, D.; Ailhaud, G.; Negrel, R. Prostacyclin is a specific effector of adipose cell differentiation. Its dual role as a cAMP-and Ca(2+)-elevating agent. J. Biol. Chem. 267:11092–11097; 1992.
Walsh, M. T.; Foley, J. F.; Kinsella, B. T. The alpha, but not the beta, isoform of the human thromboxane A2 receptor is a target for prostacyclin-mediated desensitization. J. Biol. Chem. 275:20412–20423; 2000.
Wheatley, V. R.; Brind, J. L. Sebaceous gland differentiation: III. The uses and limitations of freshly isolated mouse preputial gland cells for the in vitro study of hormone and drug action. J. Invest. Dermatol. 76:293–296; 1981.
Wilkie, N.; Morton, C.; Ng, L. L.; Boarder, M. R. Stimulated mitogen-activated protein kinase is necessary but not sufficient for the mitogenic response to angiotensin II. A role for phospholipase D. J. Biol. Chem. 271:32447–32453; 1996.
Yu, S. M.; Tsai, S. Y.; Guh, J. H.; Ko, F. N.; Teng, C. M.; Ou, J. T. Mechanism of catecholamine-induced proliferation of vascular smooth muscle cells. Circulation 94:547–554; 1996.
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Rosenfield, R.L., Wu, P.PY. & Ciletti, N. Sebaceous epithelial cell differentiation requires cyclic adenosine monophosphate generation. In Vitro Cell.Dev.Biol.-Animal 38, 54–57 (2002). https://doi.org/10.1290/1071-2690(2002)038<0054:SECDRC>2.0.CO;2
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DOI: https://doi.org/10.1290/1071-2690(2002)038<0054:SECDRC>2.0.CO;2