Effect of different FSH isoforms on cyclic-AMP production by mouse cumulus-oocyte-complexes: a time course study

The ability of different isoforms of follicle stimulating hormone (FSH) to induce accumulation of cAMP in cultured mouse cumulus-oocyte-complexes (COC ) was evaluated in a time course study. Using isoform fractions representin g less acidic (pI 6,43-5.69), mid-acidic (pI 5.62-4.96) and acidic (pI 4.69 -3.75) isoforms, the accumulation of cAMP was monitored after an exposure t ime of 0, 5, 10, 15, 30, 60, 120 and 180 min. In addition, cAMP production was monitored for 0, 5, 10, 15 and 30 min following a 5 min exposure to FSH isoform fractions, Based on FSH measurements using radioimmunoassays, the less and mid-acidic isoforms caused almost twice as much cAMP to be accumul ated than the acidic isoform fraction, thereby confirming an enhanced biolo gical activity of FSH isoforms with a isoelectric point (pI) of >5,0, For a ll isoform fractions, maximal accumulation of cAMP was achieved after 30 mi n of exposure, after which the production declined to background levels. Af ter a 5 min exposure to isoform fractions, levels of cAMP were significantl y higher in the less acidic isoform fractions, but after isoform removal, t he decline in cAMP production to background levels followed a similar time course. The results demonstrate that FSH isoforms with a pi of >5.0 induced significant biological responses within a period of 30 min and that prolon ged exposure caused attenuated signal transduction. The present results, se t in the context of the pulsatile characteristics of FSH release from the p ituitary and the reported half-life of less acidic isoforms of similar to 3 5 min, make it conceivable that isoforms with a pI >5.0 actually possess im portant physiological functions during the periovulatory period.