LH-RH and analogues of LH-RH, [2-4] LH-RH, [Lys8] LH-RH, [Ala4] LH-RH and [3-10] LH-RH were tested in vitro for their ability to stimulate LH and FSH release, respectively. Furthermore, the influence of these peptides on binding of LH-RH to the anterior pituitary plasma membrane fractions of female rats was studied to obtain some information on the structural requirements for LH-RH actions. Significant increase of LH release above the control level was recorded for LH-RH, [Lys8] LH-RH and [Ala4] LH-RH. LH release in the presence of the tripeptide [2-4] LH-RH and the octapeptide [3-10] LH-RH was statistically indistinguishable from that of basal levels. Significant stimulation of FSH release was noted only in the presence of LH-RH and [Lys8] LH-RH. Changes in the binding characteristics of LH-RH to the pituitary plasma membrane in the presence of the LH-RH analogues suggest a proportionality between releasing ability and receptor affinity. Glu and His residues of the LH molecule were found to be critical for binding to the receptor. Residual binding ability of TRH to LH-RH receptor is consistent with current molecular models of LH-RH and TRH, respectively. Furthermore, the data presented suggest that the amino acid in position 8 of the LH-RH molecule is of importance for the three dimensional structure of LH-RH.
