Regulation of Cumulus Oophorus Expansion by Gonadotropins in vivo and in vitro

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Abstract
In previous studies it was shown that highly purified follicle stimulating hormone (FSH), but not highly purified luteinizing hormone (LH) or human chorionic gonadotropin (hCG), stimulated hyaluronic acid synthesis and cumulus expansion in vitro by cumuli oophori isolated from mice primed with pregnant mare serum gonadotropin (PMSG). In contrast, it is shown here that highly purified hCG stimulated hyaluronic acid synthesis, cumulus expansion, and ovulation when injected into PMSG-primed mice. Cumulus expansion was also stimulated by hCG in ovarian organ cultures. Therefore, the action of injected hCG was probably directly on ovarian constituents. Culture of cumuli oophori in medium containing hCG was not effective in completing the cumulus expansion-stimulating processes begun by hCG in vivo. Therefore, the cumuli do not acquire the ability to respond directly to hCG in vitro as a result of the injection of hCG in vivo. This result also suggests that cumuli oophori do not respond directly to hCG in vivo. Preparations of crude follicular fluid (CFF) from PMSG-primed mice were very active in stimulating hyaluronic acid synthesis and cumulus expansion by isolated cumuli oophori. This showed that CFF contained both FSH-like activity that stimulated hyaluronic acid synthesis and the serum-like factor(s) necessary for the retention of the hyaluronic acid within the oocyte-cumulus cell complexes. PMSG stimulated the expansion of cultured cumuli oophori isolated from PMSG-primed mice and from mice not primed with PMSG. However, the PMSG priming itself did not stimulate cumulus expansion in vivo. Therefore, ample cumulus expansion-stimulating activity was potentially available to the oocyte-cumulus cell complexes in vivo as a result of PMSG-priming and in the follicular fluid, but the cumulus cells did not respond to this activity until after the hCG injection. Taken together, the results of these experiments suggest that hCG stimulates cumulus expansion in vivo by an indirect mechanism. It is hypothesized that some component(s) of the intact Graafian follicles prevents the response of the cumuli oophori to the FSH-like activity present in the follicle until that inhibition is terminated as a result of hCG administration or the endogenous LH surge.