Effects of basic fibroblast growth factor, transforming growth factor-beta and nerve growth factor on the secretory function of the bovine corpus luteum in vitro.

Abstract

The effects were investigated of basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta) and nerve growth factor (NGF) on the release of progesterone and oxytocin from the bovine corpus luteum (CL) at different stages of the oestrous cycle. A microdialysis system (MDS) of CL and a cell culture system with a reduced number of endothelial cells were used. In the MDS of CL from the mid-luteal stage (days 8-12 of the oestrous cycle), infusion with bFGF (0.1, 1, 10 and 100 ng/ml), TGF-beta (0.1, 1 and 10 ng/ml) and NGF (0.1, 1, 10 and 100 ng/ml) for 30 min induced significant acute effects on the release of progesterone. Both bFGF and NGF stimulated the release of progesterone during peptide infusion, TGF-beta and also bFGF in the period thereafter. This stimulation was dose-dependent during and after the infusion only for bFGF. This response pattern was observed at all luteal stages for the three growth factors, but bFGF was more stimulatory at the early (days 5-7) and mid-luteal stages during and after peptide infusion. The release of oxytocin was stimulated by bFGF in a dose-dependent manner. At the highest dose, bFGF, TGF-beta and NGF stimulated the release of oxytocin throughout all three luteal stages. When luteal cells were cultured with growth factors, only TGF-beta showed a dose-dependent inhibition of both basal and LH-stimulated progesterone as well as oxytocin release (measured between 48 and 52 h of culture). NGF had an inhibitory effect only on the basal release of oxytocin. bFGF had no effect on the release of either hormone under continuous stimulation in cell culture. The results indicate that bFGF, TGF-beta and NGF act directly and acutely on the secretory function of bovine CL in the MDS but also have long-term effects as shown in cell culture. bFGF appears to be an important autocrine/paracrine regulator of CL function, since local expression of its mRNA, peptide synthesis and its mitogenic and non-mitogenic actions have now been confirmed. Endothelial cells from the CL have been identified as target cells for bFGF. Differences observed between the two systems might thus be attributed to the presence or absence of cell-to-cell contact and a reduced number of endothelial cells, as well as to the duration of peptide stimulation and medium changes every 24 h compared with the flow-through conditions in the MDS.