Progesterone transcriptionally regulates the beta 2-adrenergic receptor gene in pregnant rat myometrium.
Administration of 5 mg of progesterone to late pregnant rats induced an increase in myometrial beta-adrenergic receptors density detected by 125I-cyanopindolol binding. This increase was significant after 24 h (1.4-fold; p less than 0.05) and reached 1.6-fold (p less than 0.05) after 36 h. The antiprogestin RU 486 or cycloheximide completely suppressed the effect of progesterone injection. Quantification of the beta 1- and beta 2-receptor subtypes revealed that progesterone selectively up-regulated the beta 2-subtype. The increase in beta 2-adrenoreceptors was preceded by an elevation of their mRNA (2.3 kilobases) levels as determined by Northern blot hybridization with a rat heart beta 2-adrenoreceptor cDNA probe. This increase was significant after 18 h of exposure to progesterone (2.1-fold; p less than 0.05) and reached a maximum after 24 h (3.4-fold; p less than 0.01). The rate of beta 2-adrenergic gene transcription evaluated by nuclear run-on transcription assays, increased by 2.5-fold in myometria exposed for 4 h to progesterone. This study indicates that progesterone regulates myometrial beta 2-adrenergic receptor expression by controlling the rate of transcription of the gene.
Vivat
V
V
Laboratoire de Physiologie de la Reproduction, Université Pierre et Marie Curie, Paris, France.
Cohen-Tannoudji
J
J
Revelli
J P
JP
Muzzin
P
P
Giacobino
J P
JP
Maltier
J P
JP
Legrand
C
C
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D015735:Mifepristone; D011374:Progesterone; D003513:Cycloheximide