Expression of G-protein-coupled receptor kinases in pregnant term and non-pregnant human myometrium

There is evidence for hormonal receptor desensitisation in human myometrium , but little is known about the mechanisms involved in the loss of myometri al response to agonists such as beta(2)-adrenergic agonists, prostaglandin gamma and oxytocin. It is well known that the receptors for these hormones are coupled to G-proteins. The first step of receptor desensitisation is th e phosphorylation of activated receptors by a G-protein-coupled receptor ki nase (GRK). GRKs are members of a multigene family and the various subtypes differ in their localisation, regulation and mode of action. We have used Western blotting and reverse transcription PCR to identify the GRKs present in human myometrium from pregnant and non-pregnant women as well as in cul tured human myometrial cells. We have found that human myometrium expresses the GRK subtypes 2, 4 gamma, 5 and 6. On the other hand, GRK3 and the isof orms GRK4a, beta and delta were not found in myometrial tissue. Our data in dicate that GRK2 is only expressed in pregnant term myometrium and is not f ound in nonpregnant tissue. Moreover, GRK6 appears to be expressed at a muc h higher level in pregnant term tissue than in non-pregnant myometrium. Our observations suggest that GRK2 and GRK6 may contribute to the regulation o f uterine contractility at term. Further work is necessary to determine whe ther GRKs and receptor desensitisation play a role in disorders of uterine contractility.