Desensitization of luteinizing hormone release in cultured pituitary cells by gonadotropin-releasing hormone.

Preincubation of cultured pituitary cells with GnRH caused a marked decrease in subsequent LH release. The rate of desensitization increased when the preincubating concentration of GnRH and the preincubation time were increased. Pituitary cells obtained from male rats were not as sensitive to GnRH as cells obtained from female rats and the extent of desensitization was also smaller in cells from male rats. Densensitization was found to be a long-lasting effects, without any change in the viability of the cells. A superactive analogue of GnRH (D-Phe6-GnRH) caused almost complete desensitization of LH secretion, while a competitive inhibitory analogue of GnRH caused a much smaller decrease in LH response which could be overcome by increasing the concentration of GnRH used for reincubation. These data suggest that the desensitization is closely related to the biological activity of GnRH and does not correlate with receptor binding. High concentrations of potassium also induced desensitization, although to a lower extent than GnRH. Since K+ induces LH release by a different mechanism than GnRH, our data suggest that the desensitization phenomenon cannot be explained only at the receptor level. The time curve of desensitization supports the idea that GnRH action has two-phases: an acute effect which cannot be desensitized, and a secondary phase which can be densensitized.