A TEMPORALLY INTERMEDIATE-MODE OF GONADOTROPIN-RELEASING HORMONE-INDUCED DESENSITIZATION OF LUTEINIZING-HORMONE SECRETION

The classical mode of luteinizing hormone (LH) secretory desensitizati on in the rat appears after 3-6 h of continuous in vitro administratio n of gonadotropin (GnRH). A second mode has been reported to occur ver y rapidly (<2 min) after the onset of GnRH administration, and to reve rse within 3 min after its withdrawal. Here, the existence of a third mode of desensitization is reported, occurring at 40-50 min after init iation of continuous GnRH administration. Rat pituitary cells were per ifused with 10(-8) M GnRH for 6 h; 10 min samples were collected for L H measurements by radioimmunoassay. As expected, the pattern of LH rel ease was biphasic: LH levels peaked in the first phase at 30 min, decr eased at 40-50 min, increased in the second phase to maximal levels at 90-110 min, and then decreased in the classical desensitization mode to near-baseline values by 300-360 min. Static incubations of pituitar y cells in Petri dishes in the presence of high (10(-8) M) or submaxim al (10(-9) M) GnRH concentrations confirmed the decrease in LH secreti on at 40-50 min. Measurement of LH by reverse hemolytic plaque assay ( RHPA) confirmed the existence of this new mode of desensitization; sin ce 93% of all gonadotropes had become secretory at 40-50 min, the poss ibility of two subpopulations of gonadotropes accounting for the two p hases of LH secretion appears to be ruled-out. GnRH receptor binding s tudies demonstrated a similar to 50% decrease in cell-surface binding in association with the desensitization at 40-50 min. These studies su ggest the existence of a third mode of GnRH-induced LH secretory desen sitization that is not due to gonadotrope subpopulations but may be ca usally associated with decreased GnRH receptor binding. (C) 1997 Elsev ier Science Ireland Ltd.