INDEPENDENT AND SYNERGISTIC ACTIONS OF SOMATOMEDIN-C IN THE STIMULATION OF PROTEOGLYCAN BIOSYNTHESIS BY CULTURED RAT GRANULOSA CELLS

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Abstract
The role of somatomedin-C (Sm-C) in the regulation of granulosa cell proteoglycan biosynthesis was investigated in vitro in a primary culture of rat granulosa cells labeled with [35S]sulfate. Basal [35S]sulfate incorporation into extracellular proteoglycans was increased by 93% in response to treatment with highly purified Sm-C (50 ng/ml) by itself. Whereas treatment with a minimally effective dose of FSH (20 ng/ml) alone produced a 43% increase over basal levels in extracellular [35S]sulfate-labeled proteoglycans, concurrent treatment with Sm-C yielded a 2.7-fold amplification of the FSH effect. Qualitatively similar results were obtained when [35S]sulfate incorporation into cellular proteoglycans was determined, the latter accounting for approximately one half of the total radioactivity incorporated. Significantly, fractionation of the major extracellular proteoglycan species revealed FSH to favor the exclusive production of dermatan sulfate (1.6-fold increase), whereas Sm-C supported the simultaneous biosynthesis of both heparan and dermatan sulfate (2.5- and 1.8-fold increments, respectively). Moreover, Sm-C proved capable of diverting FSH-driven proteoglycan biosynthesis from the exclusive stimulation of dermatan sulfate towards the enhanced production of heparin sulfate over dermatan sulfate. These findings suggest that while Sm-C may synergize with FSH in stimulating granulose cell proteoglycan biosynthesis, it is also able to act in its own right to effect marked quantitative as well as qualitative alterations in proteoglycan economy. Given the possible role of proteoglycans in follicular antrum formation and follicular atresia, our findings raise the possibility that Sm-C of granulose cell origin may partake in the growth as well as the demise of the developing ovarian follicle.

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