Cortisol induces rapid accumulation of whey acid protein mRNA but not of asl and b-casein mRNA in rabbit mammary explants.
Mammary explants from rabbit were cultured in the presence of various combinations of insulin, cortisol and prolactin. The concentration of whey acidic protein (WAP) asl-casein and b-casein mRNA was measured using specific cDNA probes. Medium alone was added to the explants for one day. Prolactin with and without cortisol was then added to the medium. Prolactin alone induced rapidly asl-and b-casein gene but not WAP gene. When cortisol was added with prolactin, the asl- and b-casein genes were induced at the same rate as in the absence of the steroid. In contrast, the WAP mRNA was then rapidly accumulated. This induction process was not altered by cycloheximide for two hours and it was blocked at a later stage. In a second experiment, insulin and prolactin were first added for 24 hours in the culture medium. Cortisol was then added and the concentration of the three mRNA was measured. Cortisol did not significantly modify the level of asl- and b-casein mRNA. On the contrary, the WAP mRNA was rapidly accumulated. These data indicate that the well-established amplificatory effect of glucocorticoids on casein gene expression is a slow process whereas their effect on the WAP gene is rapid. This suggests that glucocorticoids induce casein gene expression through an indirect cellular mechanism not involving a glucocorticoid receptor element in casein gene promoters and that WAP gene is more classically stimulated through the direct binding of the steroid receptor to a glucocorticoid receptor element located in its promoter.
Puissant
C
C
Unité de Différenciation Cellulaire, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
Houdebine
L M
LM
D000199:Actins / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D002364:Caseins / Q000235:genetics*; D046508:Culture Techniques; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology*; D007700:Kinetics; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008894:Milk Proteins / Q000235:genetics*; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D011817:Rabbits
D000199:Actins; D002364:Caseins; D008894:Milk Proteins; D012333:RNA, Messenger; C024471:whey acidic proteins; D011388:Prolactin; D006854:Hydrocortisone