Hormonal regulation of expression of tissue type plasminogen activator and plasminogen activator inhibitor type 1 in cultured rat granulosa cells.

In the present study, gonadotropin and gonadotropin-releasing hormone (GnRH) regulation of tPA and PAI-1 expression in PMSG-primed granulosa cells has been investigated. (i) Addition of gonadotropins (FSH and LH) and GnRH agonist (GnRHa) or PMA to the culture increases tPA activity; FSH (or LH) plus GnRHa (or PMA) in the culture further enhances the enzyme production to such an extent that a more obvious effect than the additive effect caused by these hormones used alone has been observed; (ii) in contrast, FSH and LH decrease PAI-1 activity, whereas GnRHa and PMA alone markedly increase PAI-1 mRNA level and PAI-1 activity. Because FSH and LH stimulate tPA production and have no significant effect on PAI-1 mRNA induction, the observed inhibition of PAI-1 activity by gonadotropins may be due to the occurrence of neutralization of PA and PAI-1 proteins in the conditioned media by the formation of complexes between PA and PAI-1; (iii) increases in PAI-1 mRNA level and activity by GnRH and PMA are completely inhibited by the co-addition of FSH or LH to the culture. It is, therefore, suggested that the mechanism of gonadotropin and GnRHa regulation of tPA and PAI-1 expression in granulosa cells is different.