Hyaluronic acid synthesis by mural granulosa cells and cumulus cells in vitro is selectively stimulated by a factor produced by oocytes and by transforming growth factor-beta.
In ovarian antral follicles cumulus cells (approximately 1,000/follicle) closely surround the oocyte, and mural granulosa cells (approximately 50,000/follicle) are distributed at the periphery. Previous work (Salustri, A., Yanagishita, M., and Hascall, V. C. (1990) Dev. Biol. 138, 26-32) showed that oocytes produce a factor(s) which stimulates hyaluronic acid (HA) synthesis by cumulus cells during expansion of the cumulus cell-oocyte complex. We now show that mural granulosa cells also respond in vitro to the oocyte factor(s) with greatly increased HA synthesis. As with cumulus cells, a factor(s) present in fetal calf serum is required to retain newly synthesized HA in the extracellular matrix. Unlike cumulus cells, follicle-stimulating hormone (FSH) is not required for maximal stimulation, in part because mural granulosa cells synthesize prostaglandin E2 which can substitute for FSH in promoting cumulus cell-oocyte complex expansion. Of several growth factors studied, only transforming growth factor-beta 1 (TGF-beta 1) stimulated HA synthesis in both cell types. However, the stimulation of HA synthesis by TGF-beta 1 was additive with that for the oocyte factor(s), and neutralizing antibodies to TGF-beta did not inhibit the response to the oocyte factor(s). The results indicate that the oocyte factor(s) and TGF-beta 1 are not the same and that they operate through different receptors in stimulating HA synthesis. Epidermal growth factor was able to replace FSH in amplifying the response of cumulus cells to the oocyte factor(s) and in stimulating synthesis of dermatan sulfate proteoglycans.
Salustri
A
A
Department of Sanità Pubblica e Biologia Cellulare, Faculty of Medicine, 2nd University of Rome, Italy.
Ulisse
S
S
Yanagishita
M
M
Hascall
V C
VC
D000818:Animals; D003871:Dermatan Sulfate / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006133:Growth Substances / Q000096:biosynthesis / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007700:Kinetics; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D006133:Growth Substances; D016212:Transforming Growth Factor beta; D003871:Dermatan Sulfate; D004815:Epidermal Growth Factor; D005640:Follicle Stimulating Hormone; D006820:Hyaluronic Acid; D015232:Dinoprostone