The Effect of Oral and Vaginal Administration of Synthetic LH-RH and [D-ALA 6,DES GLY 10 -NH 2 ]-LH-RH Ethylamide on Serum LH Levels in Ovariectomized,Steroid Blocked Rats 1

Summary

Effects of oral and vaginal administration of LH-RH and [D-Ala⁶, DesGly¹⁰-NH₂]-LH-RH ethylamide (D-Ala⁶-LH-RH-EA) on serum LH levels in ovariec-tomized, estrogen, progesterone treated rats were investigated. Oral administration of synthetic LH-RH induced a quick rise of serum LH levels with the greatest elevation at 15 min at any dose levels tested. On the other hand, oral administration of D-Ala⁶-LH-RH-EA resulted in a slow but progressive rise of LH during 120 min of observation. The total amount of LH released by 10 μg of the analog was much greater than the total released by 1000 μg of LH-RH. Vaginal administration of 100 μg of LH-RH mixed with Carbowax induced a progressive rise of LH which was indistinguishable from that following 10 μg of the analogue, suggesting that the potency of the analogue is 10 times greater than that of LH-RH for vaginal administration. Ten μg of LH-RH given through the vagina induced a rapid rise of LH with the peak at 15 min, whereas 1 μg of the analog induced a slow but progressive rise. Greater resistance of D-Ala⁶-LH-RH-EA than LH-RH against in vivo breakdown is postulated as one of the causes of greater and prolonged LH release by the former.