| Abstract: | The modulatory role of protein kinase C (PK-C)- and Gi-protein-mediated signal transduction systems was studied in the cyclic variation of follicle-stimulating hormone (FSH)-stimulated cAMP production of rat seminiferous tubules. FSH (Metrodin, Serono, 30 mg/1) stimulated cAMP production 10-fold (p < 0.01) in a 3 h incubation of 5 mm segments of seminiferous tubules of stages II–VI of the epithelial cycle, but only 2-fold (p < 0.01) in stages VII–VIII. The PK-C activator 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nmol/1) suppressed the FSH effect on cAMP output by 50–70% (p < 0.01) in stages II–VI, but had no effect in stages VII–VIII. If the tubular segments were preincubated for 3 h in the presence of pertussis toxin (PT, 100 μg/1), the FSH-stimulated cAMP production of stages VII-VIII increased by 100–200% (p < 0.01), and now they also became responsive to the TPA suppression. Conversely, no effect of PT was observed in stages II–VI. Cholera toxin (CT, 100 μg/1) and forskolin (Fk, 100 μmol/1) nearly similarly stimulated the cAMP production in both stages studied (about 10-fold, p < 0.01), and TPA and PT potentiated the effects in a non-additive fashion. In conclusion, both Gi-protein and PK-C-mediated mechanisms modulate cAMP production of rat seminiferous tubules. A clear cyclic variation can only be demonstrated in FSH-stimulated cAMP production, but not if the Gs-protein or adenylate cyclase are directly stimulated. Upon FSH stimulation, the low cAMP production in stages VII–VIII is mainly due to the Gi-protein-mediated inhibition. In contrast, the absence (or non-function) of this inhibition mechanism explains the brisk cAMP response to FSH in stages II–VI. PK-C activation suppresses FSH-stimulated cAMP production only if it is not inhibited by the Gi-protein-mediated mechanism (stages II–VI), probably by inhibiting the FSH-receptor-Gs-protein association. It also increases CT and Fk-stimulated cAMP production, in this case inactivating the Gi-protein. |
