The lipidosterolic extract from the saw palmetto Serenoa repens (LSESr) is commonly used for medical treatment of benign prostatic hypertrophia due to its ability to inhibit 5α-reductase which permits the conversion of testosterone to dihydrotestosterone, the active androgen on prostate cell proliferation. However, the complete action mechanism of LSESr is still unknown. Several lines of evidence suggest that, in addition to inhibition of 5a-reductase, it may interfere with the action of prolactin (PRL). We therefore investigated a possible interference of this plant extract with another hormone that controls prostate gland growth, PRL. As the action mechanism of PRL is now fully documented in Chinese hamster ovary cells expressing the PRL receptor, we have conducted our experiments on these cells. In this study, using electrophysio- logical (whole-cell recording and single-channel recording), microspectrofluo- rimetric and biochemical techniques, we show that LSESr (1-30 μ/ml) reduced the basal activity of a K^+ channel and of protein kinase C (PKC) in CHO cells. In addition, pretreatment of the cells with 1-10 μ/ml LSESr for 6-36 h abolished the effects of PRL on [Ca(2+)]i, K^+ conductance and PKC. LSESr may block PRL-induced prostate growth by inhibiting several steps of PRL receptor signal transduction. LSESr may also be useful for diseases implicating PRL.

We investigated the effects of prolactin (PRL) on the protein kinase C (PKC) activity in Chinese hamster ovary (CHO-E32) cells stably transfected with rabbit mammary gland PRL receptor cDNA. These cells express a functional long form of PRL-R. A 10-min to 2-hour treatment with 5 nM PRL resulted in the translocation of PKC activity from the cytosol to the membrane. Longer treatment ( 10-24 h) with the same concentration of PRL decreased the PKC activity in both particulate and cytoplasmic fractions. The PRL effect was dose dependent: maximal action was obtained with 1-10 nM. The PRLinduced activation of PKC was blocked by 20 nM staurosporine, a PKC inhibitor. Two inhibitors of tyrosine kinase, herbimycin A (1.75 μM) and genistein (100 μM). had no effect on PRL-induced activation of PKC.