Gonadotropin-releasing Hormone Analogue Injection Research Articles

A Randomized Trial of the Effect of a GnRH Analogue Injection on Ghrelin Levels in Girls

Introduction: Ghrelin concentrations decline during puberty by an unclear mechanism. Acylated ghrelin (AG) is unstable in sampling tubes, but no standardized sampling protocol exists. We hypothesized that ghrelin levels decrease as a consequence of increased gonadotropin-releasing hormone (GnRH) signalling and that the addition of a protease inhibitor to sampling tubes preserves the AG levels. Methods: In this randomized, placebo-controlled, cross-over study, 13 girls with suspected central precocious puberty were included. They performed an adjusted GnRH stimulation test twice and were given Relefact LHRH^® (100 μg/m²) or saline in a randomized order. Blood was sampled repeatedly for 150 min for the analysis of hormone concentrations. Oestradiol levels were only measured at baseline. The protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) was added to the sampling tubes. Specific ELISA kits were used for the analysis of AG and desacylated ghrelin (DAG) levels. Results: Neither AG nor DAG levels changed after GnRH analogue injection in comparison to saline. The addition of AEBSF preserved AG levels (650.1 ± 257.1 vs. 247.6 ± 123.4 pg/mL, p < 0.001) and decreased DAG levels (51.9 [12.5–115.7] vs. 143.5 [71.4–285.7] pg/mL, p < 0.001). Both AG and DAG levels were inversely associated with insulin levels (r = −0.73, p = 0.005, and r = −0.78, p = 0.002, respectively). AG levels were inversely associated with oestradiol levels (rho = −0.57, p = 0.041). Conclusion: Ghrelin levels do not decrease following a pharmacological dose of a GnRH analogue in the short term in girls. Addition of a protease inhibitor to the sampling tubes decreases AG degradation, resulting in preserved AG and decreased DAG levels.

Effects of GnRH-a on the ovarian maturation of blue tang fish (Paracanthurus hepatus Linnaeus, 1776)

The effects of gonadotropin-releasing hormone – analogue (GnRH-a) injection on the ovarian maturation and steroid hormone level of blue tang (Paracanthurus hepatus) females were investigated. Pre-matured blue tang females were injected with GnRH-a at dosages of 150, 200 and 250 μg/kg body weight and were then observed for fluctuation of steroid hormone levels, including testosterone (T), estradiol (E2) and 17α,20β-dihydroxy-4-pregnen-3-one (DHP) in plasma and ovary after 2 and 7 days. Plasma T level was not significantly different among the treated groups at sampling times. However, the ovarian T levels in the fish injected with 200 and 250 μg/kg GnRH-a were higher than that of the non-administered GnRH-a and fish injected with 150 μg/kg after two days (P < 0.05). After seven days of the administration, the ovarian T level was lowest in the fish without GnRH-a injection and highest in the fish injected with 250 μg/kg (P < 0.05). The plasma and ovarian E2 levels were higher (P < 0.05) in the fish injected with 200 and 250 μg/kg of GnRH-a than in the control fish after 2 and 7 days of injection. Both the plasma and ovarian DHP levels in GnRH-a injected fish were significantly (P < 0.05) increased after day 2 and was highest in the fish injected with 250 μg/kg (P < 0.05). After 7 days of injection, the plasma and ovarian DHP levels remained higher in the GnRH-a injected fish than in the controlled group (P < 0.05). There was no difference in DHP levels among the GnRH-a-treated groups. The results indicate that the dosage of 200 µg/kg of GnRH-a is appropriate for inducing maturation of the blue tang fish.

Condition of Sex Glands in the Young of the Current Year of Rainbow Trout Subjected to Surfagon Injections

Condition of sex glands and thyroid and steroid hormone levels in the blood are assessed in the young of the current year of rainbow trout cultivated in the high-mountain area of South Vietnam and subjected to injections of surfagon (synthetic analogue of gonadotropin-releasing hormone). In the conditions of the trout hatchery (Vietnam), gonads of the young of the current year are characterized by substantial anomalies, including an appearance (in addition to females and males) of hermaphrodite and sterile individuals. A single injection of surfagon 1 month after hatching leads to stabilization of the development of sex glands and decrease of the proportion of sterile individuals (from 41 to 22%). This study is the first attempt of the assessment of the effect of the injection of gonadotropin-releasing hormone analogue on the development of sex glands in the early ontogeny of fishes.

Effects of Aroclor 1254 on LH and 17,20β-P secretion in female Prussian carp (Carassius gibelio Bloch) in the spawning season

The effects of Aroclor 1254 on the secretion of luteinizing hormone (LH) and 17,20&amp;beta;-dihydroxy-4-pregnen-3-one (17,20&amp;beta;-P) in female Prussian carp (Carassius gibelio Bloch) at the time of their natural spawning were determined. Aroclor 1254 at doses of 0.01, 0.1, and 1 mg/kg body weight was dissolved in 500 ml of oil and was administered three times intraperitoneally or rectally to female Prussian carp every 24 h for three days. Blood samples were collected after 3 days of Aroclor 1254 administration to determine the LH and 17,20&amp;beta;-P concentrations using ELISA. At 6, 12, and 24 h after injection of gonadotropin-releasing hormone analogue (GnRH-A) blood samples were collected for stimulated LH secretion determination. Aroclor 1254 administered intraperitoneally (0.1 and 1 mg/kg)and rectally (0.01 and 1 mg/kg) significantly increased spontaneous LH secretion. In the case of GnRH-A-stimulated LH release, Aroclor 1254 (administered intraperitoneally only) at concentrations of 0.1 and 1 mg/kg significantly decreased gonadotropin release. The intraperitoneal injections of the lowest tested concentration of Aroclor 1254 also significantly decreased 17,20&amp;beta;-P secretion. The results show that Aroclor 1254 can affect the reproductive system of Prussian carp by changing the secretion of two very important hormones, LH and 17,20&amp;beta;-P, at the time of natural spawning. &amp;nbsp;

Menstrual History is Important for Diagnosing Catamenial Pneumothorax and Hemoptysis

Endometriosis is a chronic inflammatory gynecologic disease. Problems associated with endometriosis include dysmenorrhea, dyspareunia, and infertility. We managed two patients between March 2001 and December 2011 with extrauterine endometriosis. The first was a 37-year-old unmarried woman who was admitted for recurrent pneumothorax that was consistent with her menstrual cycle. She had received a gonadotropin-releasing hormone (GnRH) analogue injection and tibolone to prevent menopausal symptoms such as hot flashes for the past 2 years and had no recurrent pneumothorax. A 22-year-old woman arrived at the hospital with hemoptysis during menstruation, which had been occurring for the past 5 months, and chronic iron deficiency anemia. After one GnRH analogue injection per month, the hemoptysis and anemia resolved. Catamenial pneumothorax is a rare occurrence with ectopic endometriosis. Diagnosis and management are extremely crucial and difficult for the gynecologist. Our data provide an aid for managing patients with catamenial pneumothorax. doi: http://dx.doi.org/10.4021/jmc979w

Effect of Follicular Aspiration at the Onset of Progesterone-based Timed Artificial Insemination on the Follicular Dynamics and Fertility of Early Postpartum Japanese Black Cows

The effect of gonadotropin-releasing hormone analogue (GnRH-A) or follicular aspiration at the onset of progesterone-based timed artificial insemination (TAI) on subsequent follicular growth and synchronization of ovulation was examined in early postpartum Japanese Black cows. A total of 40 (22 in Exp. 1 and 18 in Exp. 2) Japanese Black cows at 20-30 days postpartum were fitted with a progesterone releasing internal device (PRID) for 7 days, injected with a prostaglandin F2α analogue upon removal of the PRID and GnRH-A 48 h later, and inseminated 18 h after GnRH-A injection. In Exp. 1, the animals were divided into three groups (untreated control, GnRH-A injection or follicular aspiration) of different treatments on the first day of PRID insertion (day 0), and the synchronized ovulation rate in the follicular aspiration group (100%; 8/8) tended to be higher (P = 0.077) than that in the control group (42.9%; 3/7). In Exp. 2, follicular growth in the GnRH (n = 9) and follicular aspiration (n = 9) groups was monitored by ultrasonography. Four out of the nine animals in the GnRH group had a corpus luteum on either day 4 or day 7 (OV group), and the other five animals had no induced ovulation (NOV group). The diameter of the ovulatory follicle on day 9 in the OV group (1.44 ± 0.11 cm) tended to be greater (P = 0.078) than that in the NOV group (1.13 ± 0.07 cm). Follicular aspiration at the onset of PRID-based TAI of early postpartum Japanese Black cows, regardless of the resumption of ovarian cyclicity, tended to result in a higher rate of synchronization of ovulation than that of the untreated controls.

Changes in Plasma Testosterone Level and Semen Quality after Frequent Injections of GnRH Analogue in a Beagle Dog with Azoospermia

A Beagle with a low plasma testosterone (T) level and azoospermia was given 10 subcutaneous injections of 1 microg gonadotropin-releasing hormone analogue (GnRH-A) per head at intervals of 3 days (Experiment 1), and 6 months after the final injection was given, 15 subcutaneous injections of 2 microg GnRH-A were given at intervals of 2 days (Experiment 2). The plasma T level increased and peaked at 8 weeks after the first injection of GnRH-A in both Experiment 1 and Experiment 2. Motile sperm were detected in the semen collected 8 weeks and 7 weeks after the first injection in Experiment 1 and Experiment 2, respectively. The total number of sperm peaked 9 weeks after the first injection in both Experiment 1 (4.5 x 10(6)) and Experiment 2 (72.8 x 10(6)).

Induction of ovulation and spawning in the Mediterranean red porgy, by controlled delivery and acute injection of GnRHa

Gonadotropin-releasing hormone analogue (GnRHa) in the form of saline injections or sus- tained-release microspheres was used to induce oocyte maturation, ovulation, and spawning in captive red porgy (Pagrus pagrus). Individually tagged vitellogenic females (n = 9 or 10) were treated at the beginning of the spawning season (March) with 20 μg/kg body weight (bw) GnRHa-loaded microspheres, a single injection of 20 μg/kg bw dissolved in saline, or physio- logical saline (control). Females were placed in tanks (one tank per treatment) connected to overflow egg collectors and monitored for 11 days. In addition to the eggs collected from the tank overflow, eggs were stripped from the fish on a daily basis. Only one spawn was obtained from the control fish, probably from a single female, given the small relative fecundity (700 eggs/kg bw). On the contrary, treatment with a GnRHa injection produced two spawns (9 and 11 days after treatment) and 50% of the fish ovulated. Treatment with GnRHa microspheres induced seven spawns (3 and 6-11 days after treatment) and 100% of the females ovulated. Females did not spawn all the eggs ovulated on a particular day, evident from the significant number of eggs obtained by manual stripping. Egg quality did not significantly differ among treatments, whereas number of spawned eggs and total relative fecundity were significantly higher in fish treated with GnRHa microspheres (ANOVA, p&lt;0.05). The results demonstrate the potential of GnRHa- loaded microspheres to induce spawning in red porgy, as a method of overcoming spawning fail- ures in commercial hatcheries.

Prevention by 17β-estradiol and progesterone of calcitonin gene-related peptide-induced elevation of skin temperature in castrated male rats

ObjectivesTo clarify the relationship between calcitonin gene-related peptide (CGRP) and ovarian hormones (17β-estradiol and progesterone) in hot flashes in men who undergo androgen deprivation therapy for prostate cancer, we studied the effects of ovarian hormones on CGRP-induced elevation of skin temperature in castrated male rats. The results were compared with those from rats treated with testosterone replacement. MethodsAdult male rats were castrated by either a single injection of gonadotropin-releasing hormone analogue (Leuplin, 1.0 mg/kg, subcutaneously) or bilateral orchiectomy. The castrated animals were subcutaneously injected daily for 14 days with ovarian hormones, testosterone, or olive oil as the vehicle. On the day after the final administration of the drug, the changes in skin temperature induced by exogenous CGRP (10 μg/kg intravenously), serum testosterone concentration, and prostate weight were measured. ResultsThe CGRP-induced elevation of skin temperature was significantly greater in the castrated rats than in the sham-treated rats. This potentiation was significantly inhibited by treatment with ovarian hormones, as well as by testosterone replacement. The testosterone replacement restored decreases in both the serum testosterone level and the prostate weight due to castration; the treatment with ovarian hormones did not affect them. Conclusions17β-Estradiol and progesterone, which do not confer testosterone activity on serum, may be useful for the treatment of hot flashes in patients for whom testosterone replacement therapy is contraindicated, such as those with prostate carcinoma. In addition, we suggest that CGRP is closely involved in the amelioration of hot flashes by ovarian hormones in men who undergo androgen deprivation therapy.

Effect of gonadotropin-releasing hormone analogue (GnRHa) and pimozide on plasma levels of sex steroids and ovarian development in sea bass ( Dicentrarchus labrax L.)

To synchronise and advance spawning, European sea bass females in late vitellogenesis were treated with two i.p. injections of GnRH analogue alone (5 and 20 μg/kg BW) given 12 h apart, or combined with pimozide (PIM) (10 mg/kg BW) either in the first or second injection. Saline-injected and untreated females were used as controls. Administration of GnRHa alone or combined with PIM accelerated the final oocyte maturation (FOM) and induced spawning. However, 48 h after the second injection the size of oocytes and the percentage of oocytes in GVBD stage were lower in the PIM-treated females. The number of eggs spawned was highest in the group that received GnRHa alone and lowest in the group that received PIM in the second injection. Plasma levels of 17β-oestradiol (E2) increased sharply at 12 h after the first injection of GnRHa alone or combined with PIM, decreasing after a second injection of GnRHa alone. However, the plasma E2 decreases was much slower in females that received the PIM in the first injection. Females that received PIM in the second injection still showed elevated plasma E2 during a longer period. Plasma testosterone (T) increase was parallel to the plasma E2 decrease and peaked earlier in the group that received GnRHa alone in both injections. Low and nonsignificant changes of 17α,20β-dihydroxy-4-pregen-3-one (17,20β-P) were observed in plasma during the time that the animals were sampled. The results demonstrate that the use of PIM does not improve the GnRHa treatment and the use of GnRHa alone during the last stages of vitellogenesis is enough to induce FOM in the European sea bass.

Gonadotropin-I and -II subunit gene expression of male striped bass (Morone saxatilis) after gonadotropin-releasing hormone analogue injection: quantitation using an optimized ribonuclease protection assay.

In fish, both gonadotropin (GtH)-I and -II are involved in the spermatogenic process, but the differential regulation of these hormones by GnRH is still poorly understood. To gain further insight into the GnRH regulation of GtH-I and -II gene expression in the male striped bass, we have developed and optimized a ribonuclease protection assay for the simultaneous measurement of all GtH subunit mRNAs in a single pituitary gland. The RNA extraction protocol enables the determination of GtH protein content in the same sample, thus enhancing the power of the method. Maturing striped bass males were injected intramuscularly with [D-Ala6,Pro9Net]-LHRH (GnRHa) and sampled at 6 and 24 h postinjection. The mRNA levels of the alpha subunit and GtH-IIbeta increased after 6 h (4- and 6-fold, respectively), while the GtH-Ibeta mRNA levels increased only 2-fold after 24 h. Interestingly, GnRHa stimulation caused a significant increase in beta-actin mRNA levels. GnRHa treatment also resulted in a 2-fold decrease in pituitary GtH-II content, associated with a dramatic increase of plasma GtH-II levels from undetectable levels (< 0.2 ng/ml) to 13+/-2 ng/ml after 6 h. These results demonstrate that both GtH-Ibeta and -Ilbeta are expressed during striped bass spermatogenesis and that the two genes are subjected to differential regulation by GnRHa.

Management of Recurrent Priapism With Epinephrine Self-Injection and Gonadotropin-Releasing Hormone Analogue

A case of recurrent priapism in a young black man without sickle cell anemia is reported. Due to almost daily episodes of prolonged painful erections, the patient was instructed in intracorporeal injection using an epinephrine self-injection kit, which provided complete detumescence on 31 occasions. The patient refused surgical intervention and was treated with monthly intra-muscular gonadotropin-releasing hormone analogue. Priapism episodes completely abated by the second and final monthly gonadotropin-releasing hormone analogue injection without recurrence during 4 months of followup. Normal erectile function was maintained during and after gonadotropin-releasing hormone analogue therapy. Epinephrine self-injection and gonadotropin-releasing priapism.

Thyroid hormones in trout reproduction: Enhancement of gonadotropin‐releasing hormone analogue and partially purified salmon gonadotropin‐induced ovarian maturation in vivo and in vitro

AbstractMaturing female rainbow trout were injected two times with gonadotropin‐releasing hormone analogue (GnRHa) or once with triiodothyronine (T3) alone or in combination. GnRHa treatment caused ovulation within 10 days after the second injection. T3 treatment caused a severalfold increase in blood plasma T3 concentrations and increased the ovulatory response to GnRHa. Ninety percent of the fish injected with both T3 and GnRHa ovulated within 3 days after the second GnRHa injection, as opposed to 50% of the fish injected only with GnRHa, or 25% of the controls. In all groups total androgen (TA) and 17α‐20β‐dihydroxy‐4‐pregnen‐3‐one (DHP) levels increased and estradiol (E2) levels decreased between the time of the first injection and the time of spawning. GnRHa decreased TA levels and increased thyroxine and T3 levels, but did not affect either E2 or DHP concentration in the blood plasma of the fish at the time of spawning. To investigate the mechanism of action of T3 on trout maturation, oocytes within intact follicles were cultured in the presence of various concentrations (0.1 to 1,000 ng/ml) of partially purified salmon gonadotropin (SG‐G100) with or without various concentrations (0.5 to 500 ng/ml) of T3. The lower concentrations of T3 (0.5 to 50 ng/ml) potentiated oocyte maturation (germinal vesicle breakdown [GVBD]) in response to SG‐G100. The highest concentration of T3 inhibited GVBD. T3 was effective in increasing GVBD only at the lowest concentration of SG‐G100 (10 ng/ml) that was effective in stimulating GVBD. The percentage of oocytes that had undergone GVBD was positively correlated with the concentration of DHP in the culture medium. These results suggest that thyroid hormones may influence final maturation of trout by potentiating the steroidogenic responses of the ovary to gonadotropin.