Progestin-dependent effect of forskolin on human endometrial aromatase acitivity

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Abstract
We have previously demonstrated that the aromatase activity in human endometrial stromal cells is stimulated by progestin and enhanced by oestrogen. In this study, we have investigated the effect of forskolin (Fit), an agent that stimulates the hormone-sensitive adenylate cydase in mammalian cells, on the intracellular cAMP content and aromatase activity in endometrial stromal cells in primary culture. Stromal cells were isolated from proliferative and secretory endometria and were individually cultured in nutrient medium or medium supplemented with medroxyprogesterone acetate (MPA), oestradiol (E2) and Fk, separately or in combination. The intracellular cAMP content of stromal cells was increased after incubation with Fk. Stromal cells treated with Fk alone or FK and MPA for 1-3 days sustained the elevated intracellular cAMP content but 90% of this nuckotide was released to the medium. Aromatase activity was either not affected or was increased up to 5-fold over the control by Fk alone. Forskolin exerted a synergistic effect upon aromatase activity in the presence of progestin or progestin and oestradiol. Sequential incubation of the stromal cells with MPA and then Fk indicated that the additional increase in aromatase activity caused by Fk occurred after 24 h of incubation. These results demonstrate that intracellular cAMP exerts a stimulatory effect on aromatase activity in progestin-conditioned stromal cells. We also investigated whether the endometrial aromatase activity changes in vivo during the reproductive cycle by measuring the activities in endometrial specimens obtained from women during their reproductive age. The mean values of aromatase activities (fmol/h x mg protein) in proliferative, secretory endometria and decidua from first trimester of the gestation were 1.6 ± 1.0 (mean ± SD, n = 10), 3.0 ± 3.4 (n = 13) and 1500 ± 900 (n = 20), respectively. These results indicate that stimulation of endometrial aromatase activity occurs after conception under physiological conditions. These observations open possibilities for the study of the role of cAMP in the expression of regulatory processes dependent upon steroid hormones in endometrial cells

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