Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LHRH antagonists compete with endogenous LHRH for binding to receptors on pituitary gonadotrophs and thereby inhibit gonadal function by suppressing gonadotropin secretion. We studied the effects of a recently developed LHRH antagonist on the pituitary-gonadal axis in man. The antagonist Detirelix [( N-Ac-D-Nal(2)1, D-pCl-Phe2,D-Trp3, D-hArg(Et2)6, D-Ala10]LHRH) was given as a single sc injection to nine normal men at three dose levels (5, 10, and 20 mg) at intervals of at least 7 days. Serum FSH, LH, and testosterone levels were measured before treatment, at frequent intervals for 48 h, and 72, 96, and 168 h after administration of the antagonist. Mean serum FSH levels decreased (P less than 0.001) from 6.9 +/- 0.5 (+/- SEM) mIU/mL to nadirs of 4.4 +/- 1.1, 3.6 +/- 0.9, and 4.1 +/- 0.9 after the 5-, 10-, and 20-mg doses, respectively. Serum LH levels decreased (P less than 0.001) from 6.2 +/- 0.3 mIU/mL to nadirs of 3.3 +/- 0.4, 2.8 +/- 0.3, and 2.7 +/- 0.3 after all three doses. Serum testosterone levels decreased (P less than 0.001) in a dose-dependent fashion from 5.1 +/- 0.2 ng/mL to nadirs of 1.3 +/- 0.3, 0.9 +/- 0.3, and 0.6 +/- 0.1 after the same doses. After the initial testosterone decrease, however, escape occurred 12-28 h after the lower doses. The area under the response curve, describing hormone concentrations as a function of time during the study, diminished by 23 +/- 2%, 36 +/- 4%, and 36 +/- 3% for FSH, by 14 +/- 6%, 30% +/- 6%, and 34 +/- 5% for LH, and by 41 +/- 5%, 58 +/- 6%, and 68 +/- 4% for testosterone with the same doses, respectively. The apparent plasma disappearance half-life of Detirelix by RIA was at least 41 h after all three doses. Detirelix elicited only a minor local reaction; no systemic side-effects were observed within the dose range used. These results indicate that this LHRH antagonist is a safe, highly potent inhibitor of the human pituitary-gonadal axis with an exceptionally long duration of action.
 ...
PMID:Suppression of pituitary-gonadal function by a potent new luteinizing hormone-releasing hormone antagonist in normal men. 310 88

A study was conducted to evaluate the effectiveness of gonadotropin-releasing hormone (GnRH) pulse infusion to stimulate follicular development and induce ovulation in seasonally anestrous standardbred mares. Seventeen mares were selected for use in this experiment, on the basis of a previous normal reproductive history, and were housed under a photoperiod of 8L:16D beginning one week prior to the start of the experiment (second week in January). Mares were infused with 20 micrograms (n = 7) or 2 micrograms (n = 6) GnRH/h, or were subjected to photoperiod treatment only (controls, n = 4). Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone did not vary, and neither significant follicular development nor ovulation was observed in any control mare throughout the experimental period (greater than 60 days). By contrast, both groups of GnRH-treated mares showed elevated serum concentrations of LH and FSH within one day after the start of infusion. Mares infused with 20 micrograms GnRH/h had at least one follicle greater than or equal to 25 mm in 7.4 +/- 1.3 (mean +/- SEM) days following the start of infusion, and ovulated in 12.0 +/- 0.7 days. In the 2-microgram-GnRH/h treatment group, a 25-mm follicle was detected in 5.7 +/- 0.7 days, and ovulation occurred after 10.0 +/- 0.3 days of infusion. Ovulation in every instance was followed by a functional luteal phase, as indicated by the profiles of progesterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Gonadotropin-releasing hormone treatment induces follicular growth and ovulation in seasonally anestrous mares. 311 2

Hormone levels, physiologic parameters, electroencephalographic (EEG) activity, and changes in subjective feelings recorded using a nonverbal instrumental device were assessed following the double-blind intravenous administration of 500 micrograms of gonadotropin-releasing hormone (GnRH) or placebo to five normal males. Within 30 minutes of GnRH administration, prolactin (PRL) levels had risen by 4.3 +/- 1.2 ng/ml (mean +/- SEM) from a baseline of 8.5 +/- 0.9 ng/ml (overall increase P less than 0.005 vs. baseline, P less than 0.001 vs. placebo); maximally stimulated values had a mean of 16.7 +/- 2.3 ng/ml. The PRL elevations measured in absolute terms significantly correlated with increases in luteinizing hormone (LH) (r = 0.97) and follicle stimulating hormone (FSH) (r = 0.89). No changes in physiologic parameters or EEG activity occurred in response to GnRH, nor were any behavioral responses found. The increase in PRL following GnRH was specifically shown to be unrelated to experimental stress or the behavioral effects of GnRH.
 ...
PMID:Effect of gonadotropin-releasing hormone on prolactin levels in males unrelated to stress or behavioral changes. 311 3

Fourteen premenopausal women with uterine leiomyomata were randomized to receive a gonadotropin-releasing hormone agonist (GnRH-a), leuprolide, either by daily subcutaneous (SC) injection (500 micrograms/day) or by intranasal (IN) spray (1600 micrograms/day) for 24 weeks. In the SC group, a significant reduction in uterine volume occurred from a pretreatment volume of 368 +/- 60 (mean +/- standard error of the mean [SEM]) cm3 to 202 +/- 61 cm3 at 12 weeks of therapy (P less than 0.01) and to 172 +/- 49 cm3 at 24 weeks of therapy (P less than 0.005). In the IN group, no significant reduction in uterine volume occurred. In addition, there was a significant negative correlation between the serum estradiol concentration during treatment and the percent decrease in uterine volume (r = -0.55, P less than 0.05). Four months after completing therapy, uterine volume increased to 296 +/- 104 cm3 in the SC group, which was not significantly different from pretreatment volume. These findings suggest that reduction in uterine volume depends on the degree of hypoestrogenism induced and that uterine volume increases soon after cessation of GnRH-a therapy.
 ...
PMID:Treatment of leiomyomata with intranasal or subcutaneous leuprolide, a gonadotropin-releasing hormone agonist. 311 33

The effects of changes in pulse frequency of exogenously infused gonadotropin-releasing hormone (GnRH) were investigated in 6 adult surgically hypothalamo/pituitary-disconnected (HPD) gonadal-intact rams. Ten-minute sampling in 16 normal animals prior to HPD showed endogenous luteinizing hormone (LH) pulses occurring every 2.3 h with a mean pulse amplitude of 1.11 +/- 0.06 (SEM) ng/ml. Mean testosterone and follicle-stimulating hormone (FSH) concentrations were 3.0 +/- 0.14 ng/ml and 0.85 +/- 0.10 ng/ml, respectively. Before HPD, increasing single doses of GnRH (50-500 ng) elicited a dose-dependent rise of LH, 50 ng producing a response of similar amplitude to those of spontaneous LH pulses. The effects of varying the pulse frequency of a 100-ng GnRH dose weekly was investigated in 6 HPD animals; the pulse intervals explored were those at 1, 2, and 4 h. The pulsatile GnRH treatment was commenced 2-6 days after HPD when plasma testosterone concentrations were in the castrate range (less than 0.5 ng/ml) in all animals. Pulsatile LH and testosterone secretion was reestablished in all animals in the first 7 days by 2-h GnRH pulses, but the maximal pulse amplitudes of both hormones were only 50 and 62%, respectively, of endogenous pulses in the pre-HPD state. The plasma FSH pattern was nonpulsatile and FSH concentrations gradually increased in the first 7 days, although not to the pre-HPD range. Increasing GnRH pulse frequency from 2- to 1-hour immediately increased the LH baseline and pulse amplitude. As testosterone concentrations increased, the LH responses declined in a reciprocal fashion between Days 2 and 7. FSH concentration decreased gradually over the 7 days at the 1-h pulse frequency. Slowing the GnRH pulse to a 4-h frequency produced a progressive fall in testosterone concentrations, even though LH baselines were unchanged and LH pulse amplitudes increased transiently. FSH concentrations were unaltered during the 4-h regime. These results show that 1) the pulsatile pattern of LH and testosterone secretion in HPD rams can be reestablished by exogenous GnRH, 2) the magnitude of LH, FSH, and testosterone secretion were not fully restored to pre-HPD levels by the GnRH dose of 100 ng per pulse, and 3) changes in GnRH pulse frequency alone can influence both gonadotropin and testosterone secretion in the HPD model.
 ...
PMID:Effects of gonadotropin-releasing hormone pulse-frequency modulation on luteinizing hormone, follicle-stimulating hormone and testosterone secretion in hypothalamo/pituitary-disconnected rams. 311 79

Plasma levels of LH, FSH, prolactin (PRL), and testosterone (T) were assessed in six normal men following administration of a pharmacologic dose of gonadotropin releasing hormone (GnRH) (500 micrograms iv over a one-min period) with concomitant oral administration of either ethanol (0.695 g/kg of body weight over a 15-min period) or ethanol placebo. Acute ethanol administration had no effect on the response of either LH or FSH to GnRH. PRL levels increased following GnRH and administration of both ethanol and ethanol placebo. Ethanol administration enhanced the T response to GnRH (p less than 0.001 vs placebo). During the placebo condition, T levels did not rise significantly until 100 min after GnRH administration, at which time the mean increment over baseline was 101 +/- 20 ng/dl (+/- SEM). In contrast, following ethanol intake, T levels were significantly elevated within 30 min after GnRH administration, at which time the mean increment over baseline was 187 +/- 42 ng/dl. The mean T increments were 304 +/- 62 and 472 +/- 77 ng/dl, respectively, 60 and 105 min following GnRH and ethanol administration. The increase in T levels following acute ethanol intake and concomitant gonadotropin stimulation is in contrast to the well-documented effect of chronic ethanol intake on suppression of testosterone synthesis by testicular Leydig cells.
 ...
PMID:Acute ethanol administration enhances plasma testosterone levels following gonadotropin stimulation in men. 312 15

This study investigated the pattern of testosterone (T) secretion in spontaneous (n = 14) and gonadotropin-releasing hormone (GnRH)-treated (n = 6) menstrual cycles in normal women. In spontaneous cycles, T was found to increase progressively over the follicular phase (P less than or equal to 0.001), with the peak T value occurring on cycle day 0 (luteinizing hormone [LH] surge). The mean (+/- standard error of the mean [SEM]) T values on cycle day -14 and cycle day 0 were 35 +/- 4 and 51 +/- 4 ng/dl, respectively. GnRH was administered intravenously to six women at 1.3 to 1.7 micrograms per dose every 30 minutes in a study that assessed the ovarian effects of a rapid gonadotropin pulse frequency. In three of the women, the T levels followed a normal follicular phase pattern, whereas in the remaining three GnRH-treated women, there were marked increases in T with peak levels of 97, 123, and 81 ng/dl on day 0. The GnRH-treated subgroup with increased T levels had significantly increased follicular levels of LH, follicle-stimulating hormone (FSH), LH-bio and number of preovulatory ovarian follicles. This study demonstrated that increased levels of LH, FSH, and LH/FSH are capable of acutely increasing the secretion of ovarian androgens.
 ...
PMID:Gonadotropin-releasing hormone-induced changes in testosterone secretion in normal women. 330 85

Gynaecomastia caused by Leydig cell tumours (LCT) in adult men may appear a long time before clinical evidence of testicular swelling. To evaluate the diagnostic criteria for LCT, hormonal status was studied in 14 cases and compared with results of a control group (CG) and 10 men with idiopathic gynaecomastia (IG). The mean plasma T level was significantly (P less than 0.005) lower in LCT (16.7 +/- 1.7 SEM nmol/l) than in CG (23.0 +/- 1.3 nmol/l). However, individual plasma T levels were in the normal range in 9/14 LCT. The mean plasma E2 level was significantly (P less than 0.001) higher in LCT (204.9 +/- 27.6 pmol/l) than in CG (87.9 +/- 7.7 pmol/l). However, individual plasma E2 levels were in the normal range in 5/14 LCT. In LCT, neither means of basal gonadotrophin levels nor the gonadotrophin responses to LHRH were different from CG. The mean of the plasma T responses to hCG did not differ between LTC, CG and IG. However the mean of E2 peak responses appeared significantly (P less than 0.005) higher in LCT (735.3 +/- 103.4 pmol/l) than in CG (420.5 +/- 40.4 pmol/l). The mean of the E2 peak responses was significantly (P less than 0.001) lower in IG (196.5 +/- 33.4 pmol/l) than in CG. Likewise the mean of plasma E2 levels, measured on day three following hCG administration, remained significantly (P less than 0.001) higher in LCT (662 +/- 94 pmol/l) than either in CG (228 +/- 14 pmol/l) or in IG (158 +/- 25 pmol/l). On day 3 following hCG administration, there was no overlap in individual plasma E2 levels between either LCT and CG or LCT and IG. In all LCT, plasma beta-hCG levels were in the normal range. A testicular echogram, performed in 12 LCT, confirmed the presence of a palpable tumour in 10 and revealed an occult tumour in two cases. We conclude that normal plasma beta-hCG levels, a prolonged plasma E2 response to hCG and testicular echogram appear to be the best criteria for early diagnosis of LCT responsible for gynaecomastia in adult men.
 ...
PMID:Evaluation of diagnostic criteria for Leydig cell tumours in adult men revealed by gynaecomastia. 330 89

Chronic treatment of adult men with LHRH agonists causes a decrease in serum testosterone and 5 alpha-dihydrotestosterone to castrate levels. In the presence of such low levels of circulating testicular androgens, the concentration of serum LH measured by radioimmunoassay (RIA) sometimes remains normal or is only partially inhibited. In order to assess the biological activity of circulating LH, we have used the mouse interstitial cell assay. Blood samples were obtained from patients with prostatic carcinoma treated with the LHRH agonist [D-Trp6] LHRH ethylamide in combination with the pure antiandrogen Flutamide (Euflex). While serum LH levels measured by RIA were only partially reduced from 2.2 +/- 0.3 (SEM) to 1.1 +/- 0.1 ng/ml after 3 months of therapy, bioactive LH was markedly inhibited from 0.43 +/- 0.04 to 0.030 +/- 0.007 ng/ml, thus causing the ratio of biologically active to radioimmunoassayable LH to drop from 0.26 +/- 0.03 to 0.03 +/- 0.01. In the same patients, serum testosterone levels were decreased from 3.91 +/- 0.51 to 0.14 +/- 0.05 ng/ml after 3 months of treatment. In patients treated for 6 months, the bio/immuno ratio was still reduced at 0.032 +/- 0.005. These data show a marked loss of LH biological activity during treatment of adult men with an LHRH agonist and an antiandrogen. The close parallelism observed between serum testosterone and bioactive LH levels suggests that the loss of biological activity of the gonadotrophin is mainly, if not exclusively, responsible for the inhibition of testicular androgen secretion observed during chronic treatment with LHRH agonists.
 ...
PMID:Loss of luteinizing hormone bioactivity in patients with prostatic cancer treated with an LHRH agonist and a pure antiandrogen. 351 4

We recently reported almost complete disappearance of serum LH biological activity in previously untreated patients with advanced prostatic cancer receiving combined therapy with a LHRH agonist and a pure antiandrogen. This decrease in LH bioactivity was most likely responsible for the fall of circulating testosterone to castration levels during such treatment. Since patients previously treated with high doses of estrogens or orchiectomy before receiving combined therapy had a less favorable response to the new treatment, we measured serum LH levels by RIA and the mouse interstitial cell bioassay in these 2 groups of patients. Serum samples were obtained from 14 men with advanced prostatic cancer treated from 9-41 months (24 +/- 9 months) with diethylstilbestrol before receiving 500 micrograms/day LHRH agonist ([D-Trp6]LH/RH ethylamide) in combination with 3 daily oral doses of 250 mg pure antiandrogen flutamide and from 21 men castrated for at least 9 months (32 +/- 26 months) before receiving the antiandrogen alone. In previously castrated patients, both bio- and immunoactive LH serum levels were elevated and did not change during at least 3 months of antiandrogen treatment. In estrogen-pretreated men, however, bioactive LH concentrations declined from 1.2 +/- 0.5 (+/- SEM) to 0.04 +/- 0.01 ng/ml after 1 month of combined treatment and remained low thereafter, while serum LH levels, measured by RIA, did not significantly decline (1.4 +/- 0.5 vs. 0.9 +/- 0.1 ng/ml on days--2 and 30, respectively). This decrease in LH biopotency caused the biological to immunological activity ratio to fall from 0.5 +/- 0.2 before the onset of the combined therapy to 0.05 +/- 0.01 after 3 months. Thus, estrogen pretreatment did not prevent the ability of the LHRH agonist-antiandrogen combination to decrease serum LH biological activity. Moreover, the absence of an effect in castrated patients receiving antiandrogen alone indicates that the LHRH agonist, and not flutamide, was responsible for the effects of the combined therapy.
 ...
PMID:Serum luteinizing hormone (LH) biological activity in castrated patients with cancer of the prostate receiving a pure antiandrogen and in estrogen-pretreated patients treated with an LH-releasing hormone agonist and antiandrogen. 352 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>