REGULATION OF MIDKINE MESSENGER-RIBONUCLEIC-ACID LEVELS IN CULTURED RAT GRANULOSA-CELLS

To investigate the regulation of ovarian midkine (MK) production at th e mRNA level, we evaluated changes in MK mRNA in cultured granulosa ce lls. The level of MK mRNA increased in a time-dependent manner in the presence of FSH or retinoic acid (RA). FSH inc;eased MK mRNA levels in a dose-dependent manner to a maximum of about 2-fold increase. The st imulatory effects of FSH were mimicked by 8-Br-cAMP. RA increased MK m RNA levels in a dose dependent manner to a maximum of about 2 fold inc rease at a concentration of 0.3 mu M These results show that granulosa cells produce MK mRNA under the independent control of FSH and RA. Th e coexistence of FSH and RA in this culture exerted no additive effect on the induction of MK mRNA. Analysis of FSH receptor mRNA induction by both reagents revealed that FSH stimulated expression of the FSH re ceptor while RA had an inhibitory effect on FSH receptor induction reg ardless of the presence of FSH. These data show that RA increases MK m RNA, and decreases FSH receptor expression, by a pathway independent o f cAMP. (C) 1996 Academic Press