Effects of adenosine analog PIA (n-phenylisopropyladenosine) on FSH-stimulated cyclic AMP (cAMP) production in the rat seminiferous epithelium.

In rat seminiferous epithelium, FSH-stimulated cAMP production is cyclically modulated by spermatogenic cells and is highest in stages XIV-V and lowest in stages VII-VIII of the epithelial cycle. Adenosine has been proposed to be an inhibitory paracrine molecule in Sertoli cells. In this paper the effect of adenosine analog n-phenylisopropyladenosine (PIA) on FSH-stimulated cAMP production was studied in staged rat seminiferous tubules. In low responsive stages VII-VIII of the cycle, 100 nM and 10 microM PIA inhibited FSH-stimulated cAMP production by 24% and 28%, respectively. To study whether PIA effect is mediated through Gi-protein, pertussis toxin (PT) pretreatment was used to block the Gi-protein. PT pretreatments of 3 or 18 h caused 42% or 16% elevation in FSH-stimulated cAMP production, respectively. PIA blocked the stimulation caused by PT pretreatment. At 38 days post irradiation, when spermatocytes and round spermatids were decreased in number, in stages VII-VIII of the cycle the inhibitory effect of PIA was abolished. In high responsive stages XIV-V of the cycle, 100 nM PIA stimulated cAMP production by 27%, while 10 microM PIA had no effect. At 38 days post irradiation FSH response was decreased by 19% when compared to non-irradiated level, and PIA stimulated FSH-stimulated cAMP production by 22%. The results suggest that there are stage-specific mechanisms for adenosine-dependent regulation of FSH-stimulated cAMP production in the rat seminiferous epithelium. Advanced spermatogenic cells seem to maintain the mechanisms that include PIA-mediated inhibition of FSH response. Other mechanisms than PT-sensitive Gi-protein seem to be involved in the inhibition.