ACTIVIN-A STIMULATES THE SYNTHESIS OF GONADOTROPIN-RELEASING-HORMONE RECEPTORS

The number of GnRH receptors on gonadotropes is regulated by GnRH as w ell as by heterologous modulators. We have used the density shift tech nique to measure the synthetic rate of GnRH receptors in pituitary cel l cultures and found it to be stimulated by GnRH, an action that is an tagonized by inhibin. In the present study, we evaluated the effects o f activin-A on the GnRH receptor synthesis rate as well as effects of activin on stimulation of GnRH receptor synthesis by the homologous ho rmone. Recombinant human activin-A (50 ng/ml) was incubated with pitui tary cell cultures from female weanling rats and the incorporation of densely labeled amino acids into receptors for GnRH was measured. The rate of GnRH receptor synthesis of cells treated with activin (50 ng/m l) together with either GnRH (0.1 ng/ml) or inhibin (12 ng/ml) was als o quantified. Activin significantly stimulated the synthetic rate of G nRH receptors similarly to that observed after GnRH treatment (time fo r synthesis of half the population of GnRH receptors was 12.6 +/- 1.1, 16.1 +/- 1.3 vs. 28.3 +/- 1.2 h for GnRH, activin, and control, respe ctively), although the time course for stimulation by GnRH and activin appeared to differ. Inclusion of activin in cultures did not affect h omologous stimulation of GnRH receptor synthesis. The stimulatory effe cts of activin were unaffected by combined treatment with inhibin (t1/ 2 of synthesis 17.2 +/- 2.0 h). Together, these data indicate that act ivin stimulates GnRH receptor synthesis in cell culture through a dist inct mechanism from GnRH. Additionally, inhibin did not antagonize the stimulatory effects of activin on synthesis of GnRH receptors. This i s, to our knowledge, the first demonstration of an action of activin-A on GnRH receptor synthesis.