Sebaceous epithelial cell differentiation requires cyclic adenosine monophosphate generation.
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 PPARalpha and PPARgamma 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 PPARalpha,delta agonist that also generates cAMP, stimulated differentiation independently of choleratoxin. Furthermore, unlike the selective PPARalpha and PPARgamma 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 beta-adrenergic catecholamines in generating cAMP. In contrast with choleratoxin, both alpha- and beta-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.
Rosenfield
Robert L
RL
Department of Pediatrics, The University of Chicago Pritzker School of Medicine, Illinois 60634-1470, USA. robros@peds.bsd.uchicago.edu
Wu
Patty Pei-Yun
PP
Ciletti
Nancy
N
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000096:biosynthesis*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D012627:Sebaceous Glands / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology
D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D002772:Cholera Toxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases