Injection Of Luteinizing Hormone-releasing Hormone Research Articles

Inhibitory effect of central LHRH on LH secretion in the ovariectomized ewe.

The role of central luteinizing hormone releasing hormone (LHRH) in the control of pulsatile LHRH and luteinizing hormone (LH) secretion was investigated in ovariectomized adult ewes. Injection of LHRH (2.1-21 pmol) into the third cerebral ventricle caused a delayed but sustained inhibition of LH secretion. Pulse frequency, pulse amplitude and mean LH levels were reduced significantly when compared with the responses to the control injection of saline (50 microliters). The inhibitory effect of centrally administered LHRH was not accompanied by a reduction in the pituitary responsiveness to intravenous LHRH. In contrast to the effect on LH, plasma levels of follicle-stimulating hormone (FSH) and prolactin were unaffected by central LHRH. The inhibitory action of LHRH was antagonized by prior injection of an LHRH antagonist ([N-Ac-D-Nal(2)1, D-p-Cl-Phe2, D-Trp3, D-hArg (Et2)6, D-Ala10] LHRH, 69 pmol) into the third ventricle. Central injection of the LHRH antagonist alone (at the same concentration) did not influence any characteristic of pulsatile LH secretion. In conclusion, these data indicate that exogenous administration of LHRH into the brain exerts a dose-related and receptor-mediated inhibition of LHRH pulse generator activity. However, the physiological significance of endogenous LHRH in the regulation of the LHRH pulse generator remains unresolved.

Inhibition of the pituitary-gonadal axis by a single intramuscular administration of D-Trp-6-LH-RH (decapeptyl) in a sustained-release formulation in patients with prostatic carcinoma.

For the past 6 years we used daily injection of luteinizing hormone-releasing hormone (LH-RH) agonists to treat patients with advanced prostate carcinoma. In this study we determined the hormonal response of the pituitary-testicular axis over a 2-month period and evaluated the safety and tolerance of the single intramuscular administration of sustained-release formulations of D-Trp-6-LH-RH microcapsules designed to release 50, 100, or 200 micrograms/day for over 1 month. Serum levels of LH, testosterone, and D-Trp-6-LH-RH were measured by RIA for up to 60 days in 10 patients with advanced prostatic carcinoma who had not received any previous drug therapy. After the administration of the microcapsules there was a biphasic increase in D-Trp-6-LH-RH serum levels. The maximal peak was obtained between 1 and 3 hr, and a second peak occurred between weeks 4 and 6. LH levels increased initially, with a maximal peak at 60 min, and elevated serum LH values persisted for more than 24 hr. LH levels began to fall on the second day, reaching subnormal values after 1 week. Serum testosterone rose during the first week and fell subsequently to less than 100 ng/dl. A rebound in LH and testosterone was seen about the 50th day after the microcapsule administration. Following the first week of therapy, we observed in all patients a significant decrease in bone pain, improvement in urinary flow obstruction, and a reversal of the signs of prostatism. No side effects were observed, and acceptance of the microcapsules was very good. Our results show that a single dose of D-Trp-6-LH-RH microcapsules suppresses of the pituitary-testicular axis for at least 50 days. D-Trp-6-LH-RH microcapsules facilitate the treatment and should lead to an improvement in the therapeutic response.

In vivo release of beta human chorionic gonadotropin by luteinizing hormone releasing hormone stimulation and its clinical application as a remission criterion in patients with gestational trophoblastic disease

In vivo responses of trophoblasts to luteinizing hormone releasing hormone (LHRH) stimulation in 48 gestational trophoblastic disease patients were observed. Serum beta human chorionic gonadotropin (β-hCG) levels after LHRH injection were significantly increased in patients with hCG values between 5 and 20 mIU/ml (minimal resistance group) but not in patients whose hCG levels were less than 5 mIU/ml (possible remission group). The sensitivity, specificity and the predictive values of LHRH stimulation test were 75.0, 91.3 and 95.5% in the possible remission group and 87.5, 20.0 and 77.8% in the minimal resistance group.

Effects of multiple injections of luteinizing hormone-releasing hormone on the induction of pregnancy in androgenized female rats.

A study of the effect of cyclic (every 4 days) administration of gonadotropin releasing hormone on reproductive performance of the androgenized female rat was carried out. The responses measured were indirect indices of increased gonadotropin output; ovulation rate, uterine decidualization, mating and implantation.

Hypothalamic-pituitary function in chronically cystic and regularly cycling dairy cows.

Studies were conducted to characterize, in detail, serum luteinizing hormone (LH) profiles 1) before and at various times after ovariectomy (OVX) in chronically cystic (CC) and regularly cycling (control) cows and 2) after injection of luteinizing hormone-releasing hormone (LHRH) and estradiol-17 beta (E2) to OVX CC and control cows. Blood samples were drawn from follicular-phase control cows and CC cows (pre-OVX) for 8 h at 15-min intervals. Cows were bilaterally OVX, and blood samples were collected for 8 h at 15-min intervals at 1, 2, and 4 wk after OVX. Five weeks after OVX, cows were challenged with 20 micrograms LHRH i.m. Six weeks after OVX, cows were challenged with 1 mg E2 i.m. Pulse frequency, pulse amplitude, and interpulse interval were not different (p less than 0.05) before or after OVX in CC and control cows. Peak LH, time to the peak, and area under the curves were not different (p greater than 0.05) after LHRH administration in CC and control cows. After injection of E2, peak LH levels were higher (p less than 0.05) in CC cows than in control cows. However, the time to the peak or the area under the curves were not different (p greater than 0.05) between groups. It appears that the feedback regulation of the hypothalamic-pituitary axis to circulating estrogen levels is altered as a result of the cystic condition.

Episodic luteinizing-hormone release in the ovariectomized female guinea pig: rapid inhibition by estrogen.

Negative feedback of estrogen was investigated in ovariectomized female guinea pigs. Two weeks after ovariectomy, indwelling catheters were inserted into the jugular vein, and 3 days later, blood samples were taken every 10 min to determine the pattern of luteinizing hormone (LH) secretion. LH secretion in these guinea pigs was episodic, with a mean pulse period of 32 min. The mean pulse amplitude was 2.1 ng/ml, with mean plasma LH levels of 1.8 ng/ml. Twenty-five micrograms 17 beta-estradiol (E2), given i.v., caused a pronounced inhibition of pulsatile LH release. Twenty-five microliters of 100% ethanol (vehicle) had no effect on plasma LH values. In a second set of experiments, ovariectomized female guinea pigs were given two injections of luteinizing hormone-releasing hormone (LHRH) (1 microgram/kg BW, i.v.) separated by 30 min. Sharp rises in serum LH values were detected after each injection. A third injection of LHRH was administered after an injection of either 25 micrograms E2 or 25 microliters vehicle. In the presence of E2, the LH response was significantly (p less than 0.005) diminished, whereas the vehicle did not change the LH response to LHRH. These rapid effects of E2 on LH secretion and the pituitary responsiveness to LHRH infusion indicate that in the ovariectomized guinea pig E2 can directly block gonadotropin secretion. These findings are consistent with the hypothesis that negative feedback actions of E2 are directly on the membrane of the gonadotrope.

Effects of LHRH on copulatory behavior and locomotor activity in sexually inexperienced male rats.

To determine whether luteinizing hormone-releasing hormone (LHRH) contributes to the sexual behavior and locomotor activity of sexually inexperienced male rats, subcutaneous injections of LHRH (500 ng) were given to males. The males showed significant facilitation of a few aspects of sexual behavior 2h after LHRH injection, compared with saline-injected controls. However, the locomotor activity of males injected with LHRH showed no significant change. These results may indicate that LHRH mechanisms play a direct role in the normal regulation of sexual arousal of male behavior in rats.

Extra-pituitary action of luteinizing hormone releasing hormone on intraocular pressure.

Luteinizing hormone releasing hormone (LHRH) given intraventricularly caused a delayed, significant decrease of intraocular pressure (IOP) in adult female rabbits for a prolonged period, but only elevated plasma gonadotropins for a few hrs. Intravenous injections of LHRH caused a similar elevation of plasma gonadotropins without any effect on IOP. It indicates that LHRH initiates a mechanism in the central nervous system to decrease IOP, which is unrelated to the conventional LHRH-gonadotropin axis.

Changes in prolactin levels caused by luteinizing hormone releasing hormone.

The acute effects of luteinizing hormone releasing hormone (LHRH) on the release of prolactin (PRL) were investigated in 12 normal cycling women and 42 women with various menstrual disorders. LHRH (100 micrograms) was bolusly injected intramuscularly and PRL levels were measured immediately before the injection and at 30 minutes and 60 minutes after the injection. LHRH elicited an increase of more than 25% in PRL levels in 15 cases (27.8%) at both 30 minutes and 60 minutes after the injection, whereas PRL levels were decreased by more than 25% in 7 cases (13.0%). The PRL response to LHRH seemed to be related to basal PRL levels. Especially when the PRL concentration was 20 ng/ml or more, LHRH decreased PRL levels in 7 cases out of 16. On the other hand, LHRH increased PRL levels in the majority of cases with a PRL concentration less than 20 ng/ml. In conclusion, the LHRH injection occasionally alters PRL levels in either a positive or negative manner, depending upon the basal PRL levels.

The response of the anterior pituitary and testes to synthetic luteinizing hormone-releasing hormone (LHRH) and the effect of castration on pituitary responsiveness in the maturing chicken fed aflatoxin.

The responsiveness of the anterior pituitary to exogenous luteinizing hormone-releasing hormone (LHRH; 20 micrograms/kg body weight) and the subsequent stimulation of testosterone secretion by the testes was studied after administration of dietary aflatoxin (10 ppm) to 9-wk-old male chickens. In both control and aflatoxin-treated males, there were significant (p less than 0.05) increases in plasma luteinizing hormone (LH) concentrations following LHRH administration, which peaked at 5 min post injection and declined thereafter. Plasma testosterone levels increased soon after the LHRH injection in control males, secondary to elevated LH levels in the peripheral circulation, and continued to increase throughout the experimental period. In contrast, this LH-induced elevation in plasma testosterone was delayed in aflatoxin-treated males, with no substantial increase until 20 min post-LHRH injection. In a subsequent experiment, castration of aflatoxin-fed males resulted in an altered response to exogenous LHRH, as compared to their intact counterparts. Based on these data, it appeared that while the LH-secretory capacity of the anterior pituitary was not diminished in birds receiving aflatoxin, the testicular response to exogenous LHRH was altered during aflatoxicosis. Additionally, the effect of castration on plasma LH profiles after LHRH administration provides preliminary evidence for extra-testicular effects of dietary aflatoxin on reproduction in the avian male.

Response of human chorionic gonadotrophin to luteinizing hormone-releasing hormone stimulation in the culture media of normal human placenta, choriocarcinoma cell lines, and in the serum of patients with gestational trophoblastic disease.

In vitro and in vivo responses to luteinizing hormone-releasing hormone (LHRH) stimulation of human chorionic gonadotrophin (hCG) production were evaluated. We cultured placental tissues of ten weeks and term pregnancy, choriocarcinoma tissues, and monolayers of the BeWo cell line, and added serial dilutions of LHRH (1, 5 and 10 micrograms) to the media for five to seven days. In in vivo experiments, 100 micrograms LHRH was intravenously administered to 20 normally cycling women (control group), 27 women who were 'possible remission', and 21 women with 'minimal resistance' to gestational trophoblastic disease. After injection of LHRH, blood samples were collected at 0, 30, 60, 90 and 120 minutes. The concentrations of immunoreactive beta-hCG in in vitro culture media, and in sera from patients, were measured before and after LHRH stimulation by double-antibody radioimmunoassay. These in vitro and in vivo experiments revealed that normal and malignant trophoblastic cells responded to the LHRH stimulation by producing immunoreactive beta-hCG. Therefore, LHRH stimulation may be useful in detecting residual choriocarcinoma cells in gestational trophoblastic disease patients during their periremission periods.

Enhanced luteinizing hormone release by luteinizing hormone-releasing hormone in incubating female turkeys (Meleagris gallopavo).

To determine what role pituitary responsiveness plays in the suppression of gonadotropin level during incubation in the turkey, the ability of the pituitary to release luteinizing hormone (LH) in response to luteinizing hormone-releasing hormone (LHRH) was compared in incubating, laying, and photorefractory birds. In all three groups, the i.m. injection of LHRH (4 micrograms/kg) increased serum LH levels; however, the LH response was markedly enhanced in the incubating turkeys as compared with the laying (6.6-fold increase over preinjection levels vs. 1.9-fold; p less than 0.05) or the photorefractory birds (9.7-fold vs. 3.1-fold; p less than 0.05). The LHRH-induced LH release was also determined in turkeys as they shifted from the laying to the incubating phase of the reproductive cycle. This response increased (p less than 0.05) in magnitude as the birds started to incubate. The high prolactin level of incubating turkeys does not have a depressing effect on LHRH-stimulated LH release; thus, impaired LH response to LHRH is not a mechanism involved in the diminished gonadotropin secretion of incubating turkeys.

Feedback regulation of gonadotropic hormone secretion in neonatal pigs.

The effect of castration and of administration of charcoal-treated porcine follicular fluid (pFF) containing inhibin-like activity on plasma concentration of gonadotropic hormones was studied in neonatal pigs. Plasma follicle-stimulating hormone (FSH) concentration averaged 25.1 +/- 1.5 ng/ml (mean +/- SEM) in 1-wk-old females and gradually declined to 20.2 +/- 0.7 ng/ml 6 wk later. Ovariectomy did not significantly influence plasma FSH concentration. In males, concentration averaged 8.0 +/- 0.7 ng/ml before castration but rose significantly within 2 days after castration. Injection of luteinizing hormone-releasing hormone (LHRH) did not influence plasma FSH concentrations in intact males, but did in females and in 7-wk-old males castrated at 1 wk. Plasma luteinizing hormone (LH) concentrations in 1-wk-old females (2.2 +/- 0.4 ng/ml) gradually declined and were not influenced by castration. Concentrations of plasma LH in 1-wk-old male piglets (2.8 +/- 0.7 ng/ml) were not significantly influenced by castration within 2 days but were significantly higher 6 wk later. LHRH induced a significant rise in plasma LH concentrations in all animals. Injection of pFF resulted in a decline of plasma FSH concentrations in intact and castrated males and in intact females, but did not influence plasma LH concentrations. These data demonstrate a sex-specific difference in the control of plasma FSH, but not in plasma LH concentration in the neonatal pig. Plasma FSH concentrations, but not plasma LH concentrations, are suppressed by testicular hormones in 1-wk-old piglets. Plasma FSH concentrations can be suppressed in both neonatal male and female pigs by injections of pFF.

Relative Importance of Dietary Aflatoxin and Feed Restriction on Reproductive Changes Associated with Aflatoxicosis in the Maturing White Leghorn Male

A study was conducted to investigate the relative contribution of dietary aflatoxin and feed restriction on reproductive and endocrine changes associated with aflatoxicosis. Pair-feeding was used to factor out nutritional and toxicological effects of aflatoxin on reproduction in the maturing White Leghorn male. Birds were randomly assigned to treatment groups at 9 weeks and fed experimental diets for 3 weeks. Experiment 1 involved the partitioning of toxicological and nutritional effects of aflatoxin on both physiological and reproductive parameters. Aflatoxin-fed males had significantly greater relative liver weights and liver lipid content than control or pair-fed males; no differences in testicular weights were found among treatments. Plasma testosterone levels in controls were significantly higher than in pair-fed birds; aflatoxin-treated males exhibited the lowest concentrations. Pituitary and testicular responsiveness to synthetic luteinizing hormone-releasing hormone (LHRH) were monitored in Experiment 2. Plasma luteinizing hormone (LH) levels in aflatoxin-fed males were significantly higher than in control or pair-fed males prior to LHRH administration. Additionally, the LH response of pair-fed birds to exogenous LHRH was qualitatively different from that observed in the other two treatments; this indicates that hormonal changes observed during aflatoxicosis and feed restriction are a result of different physiological mechanisms. Plasma testosterone also increased after LHRH injection. This response was significantly greater in controls than in pair-fed males, and nonexistant in aflatoxin-treated birds. These data indicate that there were both toxicological and nutritional effects of aflatoxin on reproduction in the maturing White Leghorn male and that these nutritional effects differed qualitatively from those observed during feed restriction. Additionally, testicular function appeared to be disrupted during aflatoxicosis.

Reproductive hormone secretion and spermatogenic function in thyroidectomized rams receiving graded doses of exogenous thyroxine.

This study aimed to obtain a better understanding of the relationship between circulating thyroxine (T4) concentrations and reproductive endocrine function in the ram. Mature Merino rams were thyroidectomized and supplemented with 0, 30, 100 and 300% of normal T4 for 10 weeks. Thyroidectomy had no apparent effect on spermatogenic function but interfered with sperm maturation, the latter being returned to normal by 30% T4 replacement. Circulating testosterone levels were reduced by thyroidectomy and restored to control levels by 30% T4; when T4 levels were supranormal (300%), circulating testosterone levels were again reduced. The lowered circulating testosterone levels in thyroidectomized rams occurred as a result of suppressed testosterone secretion from the testis, observed under basal conditions and also following LH-releasing hormone (LHRH) and human chorionic gonadotrophin injection. In thyroidectomized rams, sex hormone binding globulin (SHBG) levels were depressed without changes in testosterone clearance rate (TCR), while in rams with supranormal T4 levels, TCR was increased without changes in SHBG levels. Subnormal levels of T4 also restored to normal the reduced LH pulse frequency in thyroidectomized rams. Reduced LH pulse frequency, together with diminished LH release following LHRH injection in thyroidectomized rams, suggested effects of T4 at the hypothalamo-pituitary axis. The present study demonstrates that complete lack of thyroid hormones suppresses normal reproductive endocrine function in the ram, but that this can be restored to normal by 30% T4 replacement. The results support the theory that T4 plays a permissive rather than a regulatory role in reproductive function in males.

Effects of estradiol and mammalian LHRH on the ultrastructure of the pars distalis of the eel.

Male silver eels were injected with estradiol-17 beta (E2) to induce the development of gonadotropic (GTH) cells. They were subsequently injected with luteinizing hormone-releasing hormone (LHRH). Exocytotic figures and the lysis of some large globules and granules were observed. Morphometric studies showed a significant increase in the percentage of vacuoles after 4 and 6 injections of LHRH and a slight but significant decrease of granules. This response did not, however, occur in all GTH cells which never appeared completely degranulated and did not reach a vesicular stage. Hemi-pituitaries of E2-pretreated eels were incubated with or without LHRH (20 min to 2 h). Although typical exocytoses were not detected, an increased number of small granules near the basal lamina and lytic processes (globules with a raspberry-shaped structure, granules with variable electron density) were observed in the LHRH-incubated hemi-pituitaries compared with those kept in a control medium. The structure of GTH cells and their response to LHRH has been studied only under conditions of artificial stimulation, and their functional similarity to GTH cells of spontaneously maturing eels is discussed. Large female eels had unstimulated GTH cells. Growth hormone (STH), thyrotropic (TSH) and prolactin (PRL) cells were stimulated after E2 and LHRH. As with GTH cells, they regressed slowly after treatment was discontinued.

Effect of estradiol on the pituitary response to intravenous stimulation with luteinizing hormone-releasing hormone in menopausal women

Five menopausal patients were submitted to stimulation with 100-micrograms doses of luteinizing hormone-releasing hormone (LH-RH) administered 120 minutes apart under three different types of conditions: (1) in a hypoestrogenic state (test 1); (2) in a hyperestrogenic state after acute intravenous bolus injection of 400 micrograms 17 beta-estradiol (E2) (test 2); (3) in a hyperestrogenic state after daily oral administration of 50 micrograms ethinyl E2 for 3 to 4 weeks (test 3). The results of the three tests showed that (1) the time needed to reach maximum LH values after LH-RH injection was longest in test 3; (2) the hormonal production rate (HPR) in test 1 was greatest after the first stimulus with LH-RH. In test 2, the two stimulations with LH-RH induced an equivalent HPR, whereas in test 3, the HPR was greatest after the second stimulation; (3) the correlation between basal LH values before LH-RH injection and the maximal values of the responses obtained after each injection changed throughout the experiment. In all three tests, the slope of the line (significant positive correlation) was always greater after the second stimulation. When the three tests were compared, the slope in test 3 was greater than in test 2, and the slope in test 2 greater than in test 1. These results clearly suggest the important role of estrogens in the regulation of LH release in women by acting not only at the hypothalamus but also at the pituitary level, and demonstrate a correlation between basal LH levels and the maximum response to LH-RH stimulation. This correlation is more marked during estrogen treatment and depends on the time of exposure to estrogen.

Changes in Specialized Cognitive Function Following Changes in Hormone Levels

Increase of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in men by injection of luteinizing hormone releasing hormone (LHRH) prevented improvement in a spatial orientation test relative to a placebo condition. By contrast, performance on a fluency task was significantly increased after LHRH injection relative to the placebo condition. These data support between-subject results where FSH was negatively correlated with visuospatial skills and positively correlated with fluency.There was no change in cognitive function in males following injection of testosterone. There were also no fluctuations in cognitive function that coincided with hormonal fluctuations of the menstrual cycle in women.

Effects of long- and short-term gonadectomy on the hypothalamo-hypophysial (LH-releasing hormone-LH) system in oestrogen-treated male and female rats.

Considerable differences have previously been found in the hypothalamo-hypophysial responsiveness to oestrogen, depending upon the time between gonad removal and exposure to oestrogen. In the present study a detailed analysis was made of some of the differences which may exist in pituitary LH-releasing hormone (LHRH) receptors and the amount of LH released in response to electrochemical depolarization of the medial preoptic area after 2 or 7 days of oestradiol treatment of long- and short-term gonadectomized male and female rats. The pituitary glands of long-term gonadectomized males and females secreted more LH in response to two pulse injections of LHRH than did short-term gonadectomized rats. The amount of LH released on day 2, however, was equivalent to that secreted after 7 days of oestradiol treatment. Moreover, long-term gonadectomized males and females had equivalent LHRH receptor concentrations, which were greater than those of short-term gonadectomized animals. Peak serum LH concentrations observed after preoptic stimulation were equivalent in short- and long-term castrated rats after 2 days of oestrogen exposure. Serum LH concentrations following preoptic stimulation in short-term gonadectomized males and females were significantly greater on day 7 than on day 2 of oestradiol treatment, whereas in long-term gonadectomized animals the stimulated release of LH was equivalent both in magnitude and time of peak release on both days.(ABSTRACT TRUNCATED AT 250 WORDS)

Luteinizing Hormone Response to Pulsatile Luteinizing Hormone-Releasing Hormone in Prepubertal Heifers

The effects of 12 hourly 5-μg injections of luteinizing hormone-releasing hormone on luteinizing hormone release, were examined in 18 prepubertal Holstein heifers at 4, 7, or 10 mo of age. During a 6-h pretreatment period, mean serum luteinizing hormone concentrations and mean number of endogenous luteinizing hormone episodes per hour were not influenced by age. The 12-h treatment regimen induced a pulsatile release of luteinizing hormone in all heifers. The magnitude, pattern, and total amount of luteinizing hormone released were not influenced by age. However, in the 4 and 10-mo-old age groups, magnitude of luteinizing hormone response to the 3rd hourly injection of luteinizing hormone-releasing hormone was greater than the response to the second injection. Magnitudes of luteinizing hormone responses decreased with time after the 4th hourly injection through the 12th injection and patterns of decline appeared similar among the three age groups.The pituitary of the prepubertal dairy heifer is able to respond to an hourly pulsatile administration of luteinizing hormone-releasing hormone and this treatment regimen appears to produce a self-priming effect on luteinizing hormone release.