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.