1. Gonadotropin release during repeated administration of d-Leu6 des Gly10-LH-RH-EA at different stages of the menstrual cycle and in functional amenorrhea
J P Hanker, J Knippenberg, A J Kastin, E J Wickings, A V Schally, D H Coy, H P Schneider Int J Fertil. 1980;25(1):7-17.
A highly potent analogue of OH-RH, d-Leu6 des GLY10 LH-RH-ethyl-amide was, used to study gonadotropin release after three repeated injections of a 25-microgram dose at 3-hourly intervals. Nine volunteers at different stages of the menstrual cycle and 14 patients with functional hypothalamic amenorrhea were investigated. LH secretion varied greatly according to the functional state of the gonadostats, whereas FSH release did not show such differences. After repeated stimulation with the analogue, a tendency for diminished release of both gonadotropins was observed. Significant incremental changes of estradiol-17 beta levels occurred only after a decrease of pituitary responsiveness to further d-Leu6 des Gly10 LH-RH-EA stimuli was already evident. Therefore, it appears unlikely that estradiol-17 beta itself exerted a substantial negative feedback action on LH and FSH release in our experimental model. It is suggested that repeated administration of d-Leu6 des Gly 10 LH-RH-EA leads to changes of pituitary receptor sensitivity.
2. Effects of chronic D-Leu6, des-Gly10-gonadotropin releasing hormone ethylamide on male sex tissues
J Rajfer, D Heber, S Peng, R S Swerdloff Biol Reprod. 1984 Apr;30(3):646-51. doi: 10.1095/biolreprod30.3.646.
The chronic administration of superactive agonists of gonadotropin releasing hormone (GnRH-A) have been reported to have a direct inhibitory effect on the sex tissues of the male rat. In an attempt to confirm or refute this statement, adult male rats were either left intact or were castrated and then treated daily for 14 days with either testosterone (T), dihydrotestosterone (DHT) or sesame oil (vehicle). Half of the intact and castrate animals also received daily injections of 200 ng of the GnRH agonist, D-Leu6, des-Gly10-GnRH ethylamide for 14 days. Twenty-four hours after completing treatment, blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and T were measured by radioimmunoassay and the ventral prostate gland (VP), seminal vesicle (SV) and penis were weighed. After 2 weeks of GnRH-A treatment, the plasma T level was reduced from 2506 +/- 170 (pg/ml +/- SEM) in the intact, nontreated animals to 907 +/- 69 in the intact, GnRH-A-treated group, indicating that the dosage of GnRH-A used in this study had an inhibiting effect on T secretion. No differences were observed in the VP, SV and penile weights between the castrate, GnRH-A and the castrate, nontreated groups. When exogenous T or DHT was given for 14 days to these castrated animals, the concomitant administration of GnRH-A did not appear to have any effect on the plasma T levels or the sex accessory tissue weights. These data suggest that GnRH-A itself does not appear to have a direct inhibitory or stimulatory effect on the sex tissues of the adult male rat.
3. Stimulation of luteinizing hormone (LH) and follicle-stimulating hormone by (D-Leu6, des-Gly10-NH2)-LH-releasing hormone ethylamide after subcutaneous, intravaginal, and intrarectal administration to women
M Saito, T Kumasaki, Y Yaoi, N Nishi, A Arimura, D H Coy, A V Schally Fertil Steril. 1977 Mar;28(3):240-5. doi: 10.1016/s0015-0282(16)42432-5.
Women, most of whom had regular menstrual cycles, were administered D-Leu6,des-Gly10-NH2)-luteinizing hormone-releasing hormone (LH-RH) ethylamide (D-Leu6-LH-RH-EA)via different routes during the early or midfollicular phase of the cycle. Plasma LH, follicle-stimulating hormone (FSH), and estrogen levels were determined by radioimmunoassay before and after administration of D-Leu6-LH-RH-EA. plasma LH and FSH increased and reached peak levels 3 to 4 hours and 3 to 6 hours, respectively, after subcutaneous injection of 25 mug of the analog of LH-RH. Intravaginal or intrarectal application of 2 mg of D-Leu6-LH-RH-EA also increased plasma LH and FSH levels in most of the women, but the magnitude of the rise, the time of initiation of response, and the peak level varied among the women. The plasma estrogen level also rose after administration via either route.
