Regulation by progesterone of the high-affinity state of myometrial beta-adrenergic receptor and of adenylate cyclase activity in the pregnant rat.
The effects of pregnancy or progesterone dominance on the beta-adrenergic responsiveness of the uterus were studied in myometrial membranes from mid- and late-pregnant rats (day 15 and on the 16th h of day 22 of pregnancy respectively) or 24 h after administration of progesterone. Levels of the high (RH)- and low (RL)-affinity states of the beta-adrenergic receptor were determined by competition experiments between 125I-labelled cyanopindolol binding and the selective beta-agonist isoproterenol. The ratio KL/KH (respective dissociation constants) was determined since it also reflects the degree of formation of the high-affinity state of the beta-adrenergic receptor. From day 15 to the 10th h of day 22 of pregnancy, two distinct affinity states were apparent: 80-55% RH (KH = 0.31-0.21 microM) and 45-20% RL (KL = 14-5 microM) with a ratio of KL/KH of 55-34. In the last 6 h before birth, beta-adrenergic receptors underwent uncoupling which was paralleled by decreased responsiveness of myometrial adenylate cyclase to isoproterenol (maximum velocity (Vmax) = 17 +/- 3 vs 44 +/- 3 fmol cyclic AMP/10 min per mg protein on day 15). At this stage of pregnancy, previous exposure to progesterone resulted in a 1.8-fold increase in 125I-labelled cyanopindolol-binding sites (Bmax) and the reappearance of the high-affinity state (67% RH, KH = 0.19 +/- 0.04 (S.E.M.) microM, ratio KL/KH = 81.1 +/- 16.9).(ABSTRACT TRUNCATED AT 250 WORDS)
Cohen-Tannoudji
J
J
Laboratoire de Physiologie de la Reproduction, CNRS URA 555, Université Pierre et Marie Curie, Paris, France.
Vivat
V
V
Heilmann
J
J
Legrand
C
C
Maltier
J P
JP
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
D011943:Receptors, Adrenergic, beta; D015735:Mifepristone; D011374:Progesterone; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol