Sulfated glycosaminoglycans inhibit hyaluronic acid synthesizing activity in mouse cumuli oophori.

Prior to ovulation, the cumulus cells that surround the oocyte become embedded in a matrix containing hyaluronic acid (HA). Sulfated glycosaminoglycans (GAGs) prevent the hormonally stimulated deposition of this matrix in vitro. The goal of this project was to determine the effect of sulfated GAGs on the HA-synthesizing activity of the cumuli oophori. This activity was measured in lysates of mouse cumuli oophori after stimulation of isolated cumulus cell-oocyte complexes with follicle-stimulating hormone (FSH) in the presence or absence of sulfated GAGs. FSH treatment resulted in a 5-fold stimulation of HA-synthesizing activity by 3 h in vitro. This induction was inhibited in a dose-dependent manner by heparin and chondroitin sulfate B. However, addition of heparin or chondroitin sulfate B to the assay mixtures containing lysates of FSH-stimulated cumuli oophori had no effect on the HA-synthesizing activity. Heparin also suppressed HA-synthesizing activity stimulated by dibutyryl cyclic adenosine monophosphate. Heparin inhibited the continued increase in hyaluronic acid synthesizing activity when added to cultures after 3 h of FSH stimulation. Also, addition of heparin to cultures of cumuli oophori after 3 or 6 h of incubation in medium containing FSH resulted in only partial cumulus expansion. These results indicate that sulfated GAGs, which are found in ovarian follicular fluid and are a component of extracellular matrix, inhibit some cellular process(es) that results in increased HA-synthesizing activity. The sulfated GAGs also have the ability to suppress HA-synthesizing activity after it has been induced to levels that result in partial cumulus expansion. However, the sulfated GAGs are not direct enzyme inhibitors.