Involvement of G proteins in the effect of insulin-like growth factor I on gonadotropin-induced rat granulosa cell differentiation.

Insulin-like growth factor I (IGF-I) promotes gonadotropin-induced granulosa cell differentiation and proliferation. In order to investigate whether guanine nucleotide binding proteins (G proteins) may be linked, directly or indirectly, to some of the actions of IGF, the effects of cholera toxin (CT) and pertussis toxin (PT) on the enhancement by IGF-I of PMSG (pregnant mare serum gonadotropin)-induced rat granulosa cell differentiation have been studied. This was done by the determination of progesterone production, aromatase activity and cAMP accumulation after a 48 h incubation with PMSG, IGF-I and PMSG plus IGF-I in cells treated with either CT or PT. Both CT and PT treatment stimulated PMSG-induced progesterone production in granulosa cells after 48 h of culture with PMSG. CT treatment also stimulated aromatase activity in cells treated with PMSG and increased cAMP secretion under basal conditions (untreated cells) and in PMSG treated cells. Both CT and PT increased the stimulation by IGF-I of PMSG-induced progesterone production after 48 h of culture with PMSG plus IGF-I. Furthermore, CT augmented the enhancement by IGF-I of PMSG-induced aromatase activity and cAMP accumulation. In the absence of PMSG, CT did not increase steroidogenesis either alone or in the presence of IGF-I within the time frame studied even though CT was able to stimulate cAMP accumulation in untreated and IGF-I treated cells. These results suggest that G proteins have a role in the signalling cascade involved in gonadotropin-induced granulosa cell differentiation measured as PMSG-mediated steroidogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)