1. Direct inhibitory effect of gonadotropin-releasing hormone upon luteal luteinizing hormone receptor and steroidogenesis in hypophysectomized rats
P B Jones, A J Hsueh Endocrinology. 1980 Dec;107(6):1930-6. doi: 10.1210/endo-107-6-1930.
The effects of gonadotropin-releasing hormone (GnRH) and its potent agonist [des-Gly10, D-Leu6-N alpha Me) Leu7, Pro9,NHEt-GnRH (GnRH-A)] on ovarian luteal functions maintained by PRL were studied in vivo and in vitro. Hypophysectomized, diethylstilbestrol-treated female rats were primed with FSH for 2 days, followed by an ovulating dose of LH or hCG. Two days later, ovarian luteal functions were maintained by daily injections of 250 microgram PRL for 3 days. PRL treatment increased the serum progesterone level from 13.0 +/- 0.5 to 298 +/- 24 ng/ml and increased the ovarian hCG-binding capacity from 5.8 +/- 1.3 to 584 +/- 86 ng bound hCG/ovary. In contrast, concomitant treatment with GnRH or GnRH-A resulted in dose-dependent decreases in the PRL-induced increase of serum progesterone and ovarian LH/hCG receptor content. GnRH at 100 microgram/day caused a 60% decrease in serum progesterone and an 80% decrease in ovarian LH receptor content, whereas GnRH-A was effective at a 1-microgram dose level. Neither GnRH nor GnRH-A affected the binding affinity (Kd) of ovarian LH receptor. The direct inhibitory effects of GnRH and GnRH-A upon granulosa-luteal cell function were also tested in vitro. FSH treatment for 2 days induced functional LH and PRL receptors in cultured PRL, increased (by approximately 3-fold) progesterone production by these granulosa-luteal cells, whereas concomitant treatment with GnRH-A inhibited progesterone production in a dose-dependent manner. Thus, these studes demonstrated that GnRH and GnRH-A exert direct inhibition on ovarian luteal functions by decreasing LH receptor and progesterone production in vivo as well as inhibiting progesterone production by cultured granulosa-luteal cells in vitro.
2. The effects of an LHRH agonist on testicular function in the cryptorchid rat
D A Diamond, C Flores, S Kumar, R Malhotra, L Seethalakshmi J Urol. 1992 Jan;147(1):264-9. doi: 10.1016/s0022-5347(17)37210-5.
To assess the effects of an LHRH analog (LHRH-ethylamide des gly10 D-Leu6) on the function of the cryptorchid testis, an animal model was created, using prepubertal male Sprague-Dawley rats (21 days old). The animals were divided into six groups: 1) sham operated; 2) sham + LHRH treated; 3) cryptorchid; 4) cryptorchid + LHRH treated; 5) cryptorchid and orchidopexed; 6) cryptorchid, LHRH treated and orchidopexed. Two weeks post cryptorchidism, the animals were treated with either saline or LHRH-analog (one microgram./rat/day) subcutaneously for a total of twenty five days. Orchidopexy was performed following hormonal treatment. The effects of treatment were assessed in terms of body and reproductive organ weights, serum testosterone and LH levels, sperm counts and motility and fertility. The results demonstrated that experimental cryptorchidism impaired reproductive function, which was restored by orchidopexy, alone. Treatment of cryptorchid rats (groups 4 and 6) with LHRH did not produce any lasting improvement in spermatogenesis or fertility.
3. Pregnancy terminating effect of a highly active LH-RH agonist by vaginal application in rats
I Yamazaki Endocrinol Jpn. 1982 Apr;29(2):197-207. doi: 10.1507/endocrj1954.29.197.
A potent LH-RH agonist, des-Gly10-[D-Leu6]-LH-RH-ethylamide (TAP-144), administered to pregnant rats by the intravaginal and subcutaneous routes terminated pregnancy most effectively during days 7-11 of pregnancy. A daily administration of TAP-144 during days 7-10 was more effective by the intravaginal than by the subcutaneous route. When TAP-144 was administered twice a day during this period for one to three days, the effective dose became almost the same in the two routes. Complete termination of pregnancy occurred following a dose of 1 microgram/100 g body weight/a time by a single-day administration and 0.01 microgram/100 g body weight/a time by three days administrations. Previously we found that the serum concentration of TAP-144 after vaginal administration was lower but much longer-sustained than that after subcutaneous administration. Thus, in pregnancy termination, the prolonged duration of an effective concentration of TAP-144 seems to be more important than a transient high concentration. When rats were given effective doses of TAP-144 twice a day on day 9 by either route, ovulation occurred the next day (day 10) and the fetuses were aborted on day 11. Serum concentrations of progesterone and estradiol-17 beta dropped sharply. Estrus occurred on days 11-13, cycles were established thereafter, and ovulation occurred at regular intervals.
