EFFECT OF PREGNANCY ON PDE4, CAMP-SPECIFIC PHOSPHODIESTERASE MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN HUMAN MYOMETRIUM

In light of the important role of the second messengers cAMP and cGMP in the mechanism of relaxation in the human myometrium, specific regul ation of the phosphodiesterase (PDE) enzymatic system responsible for cyclic nucleotide inactivation is essential. We previously identified in the human myometrium PDE4 cAMP-specific PDE as by far the most abun dant isoform. Here we have studied the expression patterns of mRNAs fo r the four cloned human PDE4 genes in the myometria of pregnant and no n-pregnant women. Con current expression of the PDE4A, 4B, 4C and 4D g enes is demonstrated. We found that the PDE4D transcripts are the most prominently expressed. PDE4A and PDE4B mRNAs also are markedly abunda nt, whereas lower expression is observed for PD4C mRNAs. Interestingly , we showed that transcripts of PDE4B2 are more abundant in the myomet ria of pregnant women than in non pregnant women, whereas no differenc e between the two tissues was detected for PDE4A, 4C and 4D mRNAs. Cul tured human myometrial cells, which present a high level of PDE4 activ ity and express the four PDE4 mRNA subtypes, provide us with an approp riate model to further evaluate whether the level of expression of the PDE 4B2 mRNA subtype is under hormonal regulation. (C) 1998 Elsevier Science Inc.