PROSTAGLANDINS MODULATE HORMONAL EFFECTS ON RABBIT MYOMETRIAL ALPHA-1-ADRENERGIC RESPONSES

Estrogen increases the alpha-1-adrenergic contractile sensitivity of the rabbit uterus. Since estrogen treatment increases prostaglandin (PG) production by the perfused rabbit uterus, and PGs contribute to the alpha-1-adrenergic contractile response, we postulated that estrogen's effects on PG production or response may play a role in the increased alpha-1-adrenergic sensitivity induced by estrogen. We studied the effects of the eicosanoid synthesis inhibitor meclofenamate (60-mu-M) on the response to epinephrine (10(-9)-10(-5) M) of uterine strips from ovariectomized, mature, and estrogen-treated rabbits in terms of both contractile response and PGE2 and PGF2-alpha production. We also measured the contractile response to PGE2 and PGF2-alpha (both 10(-10)-(10(-5) M) and KCl (70 mM) of uterine strips from these groups. We found that in the ovariectomized rabbits, meclofenamate decreased PG production, but did not alter the alpha-1-adrenergic sensitivity. In the mature rabbit uterus, meclofenamate decreased both PGE2 and PGF2-alpha production and reduced the alpha-1-adrenergic sensitivity. In the estrogen-treated rabbit uterus, meclofenamate decreased PGF2-alpha, but not PGE2, production and did not alter the alpha-1-adrenergic sensitivity. Finally, meclofenamate reduced the contractile response to KCl in all three groups, and exposure to PGE2 increased the contractile response to KCl in both the mature and estrogen-treated rabbits. We conclude that PGs play a role in the increase in the alpha-1-adrenergic sensitivity of the uterus in mature rabbits, and that this may be the result of an estrogen-mediated alteration in the postreceptor effects of PGs.