Injection Of Luteinizing Hormone-releasing Hormone Research Articles

The Effect of Copper–Cadmium Co-Exposure and Hormone Remediation on the Ovarian Transcriptome of Nile Tilapia (Oreochromis niloticus)

The escalating problem of copper (Cu) and cadmium (Cd) pollution in aquatic environments poses a significant threat to the ovarian tissue and reproductive capacity of fish, hindering the development of the aquaculture industry. However, the combined effects of Cu and Cd on fish gonadal development remain unclear. In this study, the fish species Nile tilapia was stressed with rearing water containing 300 μg/L Cu2+ and 100 μg/L Cd2+ for 30 days, followed by an intraperitoneal injection of luteinizing hormone-releasing hormone (LHRH-α) and human chorionic gonadotropin (HCG) at various concentrations. We investigated the ovarian transcriptome profiles before and after injection. Prior to injection, combined treatment with Cu and Cd resulted in reproductive dysfunction and metal ion imbalance in tilapia. Transcriptomic profiling revealed differential gene annotation concentrated in the MAPK signaling pathway and regulation of GTPase activity. Post-injection, all concentrations of LHRH-α and HCG groups showed an upregulated gonadosomatic index (G.S.I) and higher levels of vitellogenin (VTG), gonadotropin-releasing hormone (GnRH), gonadotropin (GTH), and estrogen (E2) in serum compared to the negative control group. Transcriptomic analysis revealed alterations in various ovarian signaling pathways, preliminarily revealing the in vivo molecular mechanisms and differences in LHRH-α and HCG. The findings from this study could help us better understand how to counteract the effects of combined Cu and Cd exposure on tilapia ovarian development, which has significant implications for the Nile tilapia aquaculture industry.

Influence of thyroxine on spawning performance and larval development of Sterlet sturgeon Acipenser ruthenus

This study set out to examine the effects of thyroxine (T4) on reproductive success of female Sterlet sturgeon broodstock and subsequent growth and development of the larval offspring. Fish received four intraperitoneal injections of coconut oil (controls), 1 mg T4/kg body weight (BW) in coconut oil (T1) or 10 mg T4/kg BW in coconut oil (T10) over a 170-day treatment period. Ovulation was induced by intramuscular injection of luteinizing hormone-releasing hormone (LHRHa2). Fish in the control group ovulated quicker and had higher fecundity than the fish in experimental groups. Oocyte diameter was highest in the T10 group. Hatching rate in the control group was lowest among the groups. Larval survival at 3 days post hatch in T10 group was 92.2% and was highest among the treatments. Larval survival and the specific growth rate were greater in T10 than in the other treated groups. The T4 concentrations in unfertilized eggs, pre-larvae and post-larvae were higher in the T10 group than the others. These results showed the maternal injection of T4 has stimulatory effects on larval hatching rates, survival, and growth which make it a valuable treatment in sturgeon aquaculture.

The Relationship between Hot Flashes and Testosterone Recovery after 12 Months of Androgen Suppression for Men with Localised Prostate Cancer in the ASCENDE-RT Trial

AimsThis study describes the proportion of men who experienced hot flashes (flashes), and the testosterone level at onset, peak frequency and cessation of flashes after 12 months of androgen deprivation therapy (ADT) in men undergoing curative-intent external beam radiation therapy (± brachytherapy boost). We also aimed to characterise testosterone recovery in this population. Materials and methodsThis was a pre-specified secondary analysis of the ASCENDE-RT clinical trial. Three hundred and ninety-eight men were randomised. All received 12 months of ADT. The presence and frequency of flashes were patient reported. Cessation of flashes was defined as the first date a patient reported resolution of this symptom. Testosterone recovery was defined as any single serum testosterone above the threshold of 5, 7.5 or 10 nmol/l. ResultsThe median age and follow-up were 68 years and 6.1 years. Flashes were reported in 93% of men. Flashes began and reached peak frequency at a median time of 4.0 months from the first luteinizing hormone-releasing hormone injection when testosterone levels had fallen to castrate. The median time to cessation of flashes was 7.6 months after the cessation of ADT (last injection + 3 months), when the median testosterone had risen to 5.7 nmol/l. A resolution of flashes was reported in 99% of patients. Baseline testosterone was available in 338 patients (85%). The median baseline testosterone was 13.2 nmol/l. The median (95% confidence interval) time of testosterone recovery to thresholds of 5 nmol/l, 7.5 nmol/l and 10 nmol/l were 9 (9–10) months, 13 (10–15) months and 18 (17–19) months from the cessation of ADT. At the time of censor, 96, 94 and 91% of patients had recovered testosterone to thresholds of 5, 7.5 and 10 nmol/l. ConclusionFlashes occur at castrate levels of testosterone, with cessation of hot flashes antedating full recovery of testosterone in most patients. Rates of testosterone recovery after 12 months of ADT exceed 90%, although it can be delayed.

The participation of the muscarinic receptors in the preoptic-anterior hypothalamic areas in the regulation of ovulation depends on the ovary.

BackgroundMuscarinic receptors (mAChRs) of the preoptic and anterior hypothalamus areas (POA-AHA) regulate ovulation in an asymmetric manner during the estrous cycle. The aims of the present study were to analyze the effects of a temporal blockade of mAChRs on either side of the POA-AHA performed in diestrus-2 rats on ovulation, the levels of estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) and the mechanisms involved in changes in ovulation.MethodsCyclic rats on diestrus-2 day were anesthetized and randomly assigned to the following groups: 1) microinjection of 1 μl of saline or atropine solution (62.5 ng) in the left or right POA-AHA; 2) removal (unilateral ovariectomty, ULO) of the left (L-ULO) or right (R-ULO) ovary, and 3) rats microinjected with atropine into the left or right POA-AHA plus L-ULO or R-ULO. The ovulation rate and the number of ova shed were measured during the predicted estrus, as well as the levels of estradiol, FSH and LH during the predicted proestrus and the effects of injecting synthetic LH-releasing hormone (LHRH) or estradiol benzoate (EB).ResultsAtropine in the left POA-AHA decreased both the ovulation rate and estradiol and LH levels on the afternoon of proestrus, also LHRH or EB injection restored ovulation. L- or R-ULO resulted in a lower ovulation rate and smaller number of ova shed, and only injection of LHRH restored ovulation. EB injection at diestrus-2 restored ovulation in animals with L-ULO only. The levels of estradiol, FSH and LH in rats with L-ULO were higher than in animals with unilateral laparotomy. In the group microinjected with atropine in the left POA-AHA, ovulation was similar to that in ULO rats. In contrast, atropine in the right POA-AHA of ULO rats blocked ovulation, an action that was restored by either LHRH or EB injection.ConclusionsThese results indicated that the removal of a single ovary at noon on diestrus-2 day perturbed the neuronal pathways regulating LH secretion, which was mediated by the muscarinic system connecting the right POA-AHA and the ovaries.

ASCENDE-RT*: A multicenter, randomized trial of dose-escalated external beam radiation therapy (EBRT-B) versus low-dose-rate brachytherapy (LDR-B) for men with unfavorable-risk localized prostate cancer.

3 Background: This trial compared the efficacy of DE-EBRT and LDR-B for National Comprehensive Cancer Network (NCCN) high and intermediate-risk disease. Methods: A planned sample size of 400 patients were randomized to one of two treatment arms and stratified by risk group. Both arms received 12 months of androgen deprivation therapy (ADT) with luteinizing hormone releasing hormone (LHRH) agonist plus a non-steroidal anti-androgen for at least 1 month. After 8 months of neo-adjuvant ADT, both arms received whole pelvis EBRT (46Gy/23#). Patients assigned to DE-EBRT (standard arm) then received a conformal EBRT boost (32Gy/16#). Patients assigned to LDR-B (experimental arm) received an Iodine-125 LDR boost prescribed to a minimum peripheral dose of 115Gy. The primary endpoint was relapse free survival (RFS) defined by biochemical criteria using the nadir+2 ng/mL threshold. Time zero was the date of the first LHRH injection. Results: Between Dec 2002 and Sep 2011, 276 high-risk and 122 intermediate-risk patients were accrued at 6 cancer treatment centers. 200 men were assigned to DE-EBRT and 198 to LDR-B. The treatment arms were well balanced in terms of age and known prognostic factors. Median follow up (FU) is 6.5 years; 65 men have >9 years FU. There were 12 major protocol violations in each arm. By intent-to-treat analysis, the 3-, 5-, 7-, and 9-year Kaplan-Meier RFS estimates are 94% vs 94%, 77% vs 89%, 71% vs 86%, and 63% vs 83% for DE-EBRT and LDR-B respectively (hazard ratio = 0.473; 95% CI 0.292 – 0.765; P = 0.0022). Randomization (p<0.001), percent positive cores (p=0.005), initial PSA (p=0.006) and clinical T-stage (p=0.013) were predictive of RFS in a multivariable Cox model. The median PSA at latest FU for non-relapsing patients assigned to LDR-B is 0.02 vs 0.24 ng/mL for DE-EBRT. Conclusions: In a randomized trial, an Iodine-125 LDR boost was much more effective than an EBRT boost in rendering unfavorable-risk prostate cancer patients biochemically disease free. *ASCENDE-RT- Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy is an NCI registered trial (NCT00175396). Clinical trial information: NCT00175396.

Seasonal changes in oocyte maturational competence, ovulatory competence and gonadotropin sensitivity of ovarian follicles in hybrid sturgeon, bester (Huso huso × Acipenser ruthenus )

Oocyte maturation and ovulation in sturgeon species are induced by injection of hormones such as the luteinizing hormone-releasing hormone (LHRH). Appropriate timing for the LHRH injection is determined by monitoring the maturational stage of the ovarian follicles. In the present study, ovarian follicles from a group of female bester sturgeon (Huso huso × Acipenser ruthenus) were sampled continuously from September to May and incubated in 100% L-15 medium (pH 8.2) containing 17α-hydroxyprogesterone or salmon pituitary extract (SPE) for 48 h at 15°C. After incubation, ratios of oocyte maturational competence (OMC; ability of oocytes to undergo final oocyte maturation in response to maturation-inducing steroid, MIS), ovulatory competence (OC; ability of ovarian follicles to ovulate under MIS stimulation), and GTH sensitivity (ability of ovarian follicles to respond to GTH) were examined. Almost all oocytes maintained OMC throughout the sampling period. However, OC was acquired in circa December and May. The ratio of follicles that acquired ovulatory competence showed wide variation among individuals. Most females first acquired a higher degree of ovulatory competence in May, although some only did so around December. SPE-induced oocyte maturation was relatively high throughout the entire experiment, and the ovulation rate showed a tendency similar to that of the ovulatory competence. LHRH-a injections in May successfully induced ovulation in all females. Higher hatching rates resulted in females whose ovarian follicles showed an increasing trend of ovulatory competence and GTH sensitivity for ovulation in May. These results indicate that ovulatory competence and GTH sensitivity can be used as indicators to determine the timing of LHRH injections for sturgeon.

Incomplete testosterone suppression with luteinizing hormone‐releasing hormone agonists: does it happen and does it matter?

What's known on the subject? and What does the study add? Previous reports, with small numbers of patients, have described the problem of incomplete testosterone suppression (>1.1 or 1.7 nmol/L) with LHRH agonists. Various predisposing factors have been suggested: different drug agents and patient factors such as age, pretreatment testosterone levels and weight. Such incomplete testosterone suppression has been shown in one small report to be associated with increased PSA failure rates and in another report in those with metastases, with worse survival. This study used testosterone assays that are more accurate at low levels than those used in most previous reports in a large dataset of 2196 men, and confirmed incomplete testosterone suppression (breakthrough) rates >1.7 nmol/L of 3.4% and >1.1 nmol/L of 6.6%. We showed that younger age was strongly associated with the risk of breakthrough, with a minor effect of increasing body mass index. Repeated breakthroughs were more common (16%) in those who had already had one breakthrough. Interim measures of cancer control (PSA kinetics during LHRH therapy) were inferior in those with a breakthrough, and those with breakthroughs between 1.1 and 1.7 nmol/L had worse long-term biochemical control rates. • To describe breakthrough rates above castrate levels of testosterone, in a population-based series of men undergoing adjuvant luteinizing hormone-releasing hormone (LHRH) agonist therapy with curative radiation therapy. • To explore the predisposing factors for such breakthroughs and their impact on subsequent outcomes. • All men treated for prostate cancer between 1998 and 2007 with curative radiation in the province of British Columbia, Canada were potentially eligible (n= 11752). Of these, 2196 fulfilled the eligibility criteria. • Serial testosterone measurements were obtained during continuous LHRH therapy. • Breakthrough rates >1.1 nmol/L and >1.7 nmol/L were calculated for each LHRH injection and for each patient course. • Predisposing factors were identified, and early surrogates of oncological outcome (neoadjuvant nadir and post-treatment nadir) were determined. • The risk of a breakthrough >1.1 nmol/L was 6.6%, and >1.7 nmol/L was 3.4% per patient course and 5.4% and 2.2% per LHRH injection (inclusive ranges). • Repeated breakthroughs occurred in 16% of patients. • Younger men were more liable to breakthroughs (P < 0.001). • Early PSA kinetic surrogates of cancer control were inferior in those with breakthroughs. • Neither overall biochemical non-evidence of disease (bNED) nor survival were compromised, although subgroup analysis showed inferior 5-year bNED in those with breakthroughs of 1.1-1.7 nmol/L vs those without (58% vs 73%, respectively; P= 0.048). • Breakthroughs with LHRH agonists occur occasionally per injection, but occur commonly per patient course of treatment, and adversely affect early surrogate measures of outcome. • The monitoring of testosterone levels during therapy is therefore advised.

Effect of priming injections of luteinizing hormone-releasing hormone on spermiation and ovulation in Gϋnther's Toadlet, Pseudophryne guentheri

BackgroundIn the majority of vertebrates, gametogenesis and gamete-release depend on the pulsatile secretion of luteinizing hormone-releasing hormone (LHRH) from the hypothalamus. Studies attempting to artificially stimulate ovulation and spermiation may benefit from mimicking the naturally episodic secretion of LHRH by administering priming injections of a synthetic analogue (LHRHa). This study investigated the impact of low-dose priming injections of LHRHa on gamete-release in the Australian toadlet Pseudophryne guentheri.MethodsToadlets were administered a single dose of two micrograms per. gram LHRHa without a priming injection (no priming), or preceded by one (one priming) or two (two priming) injections of 0.4 micrograms per. gram LHRHa. Spermiation responses were evaluated at 3, 7 and 12 hrs post hormone administration (PA), and sperm number and viability were quantified using fluorescent microscopy. Oocyte yields were evaluated by stripping females at 10-11 hrs PA. A sub-sample of twenty eggs per female was then fertilised (with sperm obtained from testis macerates) and fertilisation success determined.ResultsNo priming induced the release of the highest number of spermatozoa, with a step-wise decrease in the number of spermatozoa released in the one and two priming treatments respectively. Peak sperm-release occurred at 12 hrs PA for all priming treatments and there was no significant difference in sperm viability. Females in the control treatment failed to release oocytes, while those administered an ovulatory dose without priming exhibited a poor ovulatory response. The remaining two priming treatments (one and two priming) successfully induced 100% of females to expel an entire clutch. Oocytes obtained from the no, or two priming treatments all failed to fertilise, however oocytes obtained from the one priming treatment displayed an average fertilisation success of 97%.ConclusionSpermiation was most effectively induced in male P. guentheri by administering a single injection of LHRHa without priming. In contrast, female P. guentheri failed to ovulate without priming. A single priming injection induced the release of oocytes of high viability compared to oocytes obtained from females in the two priming treatment which underwent a process of over-ripening.

Significance of measured elevation of skin temperature induced by calcitonin gene-related peptide in anaesthetized rats

To assess whether peripheral changes related to skin temperature rise were induced by ovarian hormone deficiency, we investigated the effects of anaesthesia on calcitonin gene-related peptide (CGRP)- or luteinizing hormone-releasing hormone (LH-RH)-induced elevation of skin temperature in female rats. CGRP was used as an inducer of peripherally-mediated elevation of skin temperature, whereas LH-RH was used as an inducer of centrally-mediated elevation of skin temperature. Intravenous (i.v.) but not intracerebroventricular injection of CGRP (10 microg kg(-1)) or intracerebroventricular but not intravenous injection of LH-RH (10 microg/rat) elevated the skin temperature of unanaesthetized rats restrained in a Ballman's cage. The elevation with LH-RH was completely inhibited by urethane anaesthesia, whereas the elevation with CGRP was not. These results suggested that changes in skin temperature measured under anaesthesia reflected a peripherally rather than a centrally mediated mechanism. The CGRP (1.0-30 microg kg(-1), i.v.)-induced elevation of skin temperature was potentiated in ovariectomized rats and inhibited by pretreatment with a CGRP receptor antagonist CGRP(8-37) (1000 microg kg(-1), i.v.), suggesting that the potentiation may participate in peripheral factors such as a postsynaptic hypersensitivity to CGRP following ovarian hormone deficiency. Thus, measurement of skin temperature in the anaesthetized rat was a useful procedure to seek the peripheral mechanism of potentiation of skin temperature induced by CGRP, thought to be closely related to menopausal hot flashes.

Adverse Effects of Environmental Toxicants, Octylphenol and Bisphenol A, on Male Reproductive Functions in Pubertal Rats

It has been proposed that a global decline in sperm counts, semen quality, and several male reproductive disorders are associated with exposure to environmental chemicals. Thus, the present study examined the effects of two estrogenic chemicals, octylphenol (OP) and bisphenol A (BPA), on epididymal sperm counts and sperm motility, luteinizing hormone (LH)-releasing hormone (LHRH)-stimulated plasma LH and steroid hormones, insulin-like growth factor I (IGF-I), and accessory reproductive organs in pubertal male Wistar rats. Fifty-day-old rats in the OP group (n=11) and BPA group (n=11) received daily sc injections of the respective chemical at a dose of 3 mg/kg bw dissolved in 0.2 mL DMSO. Rats in the control group (DMSO group; n=10) received 0.2 mL DMSO alone. After 2 wk of treatment, a jugular blood sample was taken, and, on the next day, a second blood sample was taken 1 h after an sc injection of LHRH (250 ng). After 5 wk of treatment, rats were deeply anesthetized and heart blood was collected. Epididymal sperm motility and sperm head counts were determined. LHRH increased plasma LH to higher levels in all groups, but the increases were significant (p<0.01) in the BPA and OP groups. However, despite higher LH levels after LHRH injection, the incremental responses of testosterone and pro-gesterone in the OP and BPA groups were small compared to those in the DMSO group, which showed a small LH response. After 5 wk of treatment, plasma testosterone levels were significantly (p<0.01) reduced in the OP and BPA groups and this was accompanied by reduced (p<0.05) epididymal sperm counts. However, the chemical-treated groups had high basal progesterone levels. No significant effects of chemicals on sperm motility parameters were noted. The chemical-induced increases (p<0.05) of the weight of ventral prostate gland were coincided with elevated plasma IGF-I levels in the BPA (p<0.05) and OP (p<0.01) groups. The present results demonstrated that OP and BPA can reduce sperm counts resulting from lowered plasma testosterone in male rats just after puberty. The enlarged ventral prostate gland may possibly be associated with increased plasma IGF-I, raising the possibility of a link between these chemicals and prostate diseases because IGF-I has been implicated in the pathogenesis of human prostate cancers.

Influence of LHRH on sex hormone receptors in the amygdala of the male rat

Autoradiography was used to localize estrogen-accumulating cells in the amygdala (AMY), of male rats. with LHRH hormones of seven adult male rats (86 days old). Seven mail rats were each treated with an injection of luteinizing hormone-releasing hormone (LHRH, 25 μg) at 83 days old and 3 days later with 250 μCi 3H-estradiol (E2). A control group of male rats was also treated with 250 μCi 3H-E2, two hours before sacrifice. Both groups were sacrificed at 86 days old. In the control group of male rats, the nuclei of the AMY with the highest density of estrogen binding (receptors) were nucleus medialis (NM), nucleus corticalis (NCO), nucleus centralis (NCE) and massa intercalata (MI) of pars corticomedialis of AMY. These nuclei belong to the phylogenetically older corticomedial part of the AMY. Light to moderate labeling was present in the phylogenetically younger nucleus basomedialis (NBM) and nucleus basolateralis (NBL). Weak labeling was present in nucleus lateralis anterior (NLA) and nucleus lateralis posterior (NLP) both from the phylogenetically younger basolateral part of the adult male rat AMY. This distribution of estrogen receptors could be related to the biologically more significant influence of estrogen on the regions of response divergence than on regions of sensory convergence of AMY. In the male rats treated with LHRH 3H-E2, we noticed different a distribution of estrogen receptors, in the different types nuclei of neurons (nucleus of AMY). We observed a smaller number of estrogen receptors in the nucleus of pyramidal neurons, while in fusiform and stellate neurons, a similar number of receptors was present as in the control group for NM, NCO, and NCE. In massa intercalata we found a large numberof receptors in the nuclei of neurons, in the older pars AMY. In younger pars AMY, NBL and NLP, we noticed a significant decrease of receptors for estradiol in the nuclei of pyramidal and fusiform neurons.

Hormonal therapy for patients with advanced adenocarcinoma of the prostate: is there a role for discontinuing treatment after prolonged androgen suppression?

Objectives To determine the hormonal (luteinizing hormone [LH], testosterone) and biochemical (prostate-specific antigen [PSA]) response to withdrawal of LH-releasing hormone (LHRH) agonist therapy for patients with prostate cancer with an undetectable PSA who received this treatment for an extended period. Methods Four selected patients older than 70 years of age with advanced adenocarcinoma of the prostate who were treated with a depot injection of LHRH and antiandrogen therapy had their treatment discontinued. During the period of total androgen blockade, each patient obtained and maintained a persistent undetectable PSA level. After cessation of androgen blockade, patients underwent serum measurements of PSA and testosterone at baseline and then every 6 months for 36 months. Serum LH was performed at baseline and then at 6, 18, and 36 months. Results At the time androgen ablative therapy was discontinued, patients had received LHRH agonist/antiandrogen therapy for a mean of 108 months (range 94 to 120). All 4 patients had castrate levels of testosterone (less than 0.5 ng/mL) and undetectable levels of PSA at baseline and with continued monitoring. At 6 and 18 months, all patients except one had LH levels in the normal range. All 4 patients remained clinically asymptomatic throughout the follow-up period with undetectable PSA levels. Conclusions Withdrawing hormonal therapy in asymptomatic patients with advanced prostate cancer after prolonged total androgen blockade was noted to be safe and effective in elderly patients who had achieved an undetectable PSA level. It appears that reduced testosterone levels may be a result of altered and potentially irreversible Leydig cell function rather than continued suppression of the hypothalamic-pituitary-testicular axis.

Differential response of prostate specific antigen to testosterone surge after luteinizing hormone-releasing hormone analogue in prostate cancer and benign prostatic hyperplasia.

To investigate any differences in changes in serum prostate specific antigen (PSA) levels in patients with benign and malignant prostatic disease in response to the testosterone surge after administering a luteinizing hormone-releasing hormone (LHRH) analogue. The study included 54 patients referred to the urology clinic with intermediate PSA levels (4-10 ng/mL) or an abnormal digital rectal examination. Forty-five patients received a single injection of LHRH analogue depot each at one week before prostate biopsy and nine served as a control group. Changes in PSA levels in response to the testosterone surge from the LHRH analogue were recorded after 5 and 7 days, and were correlated with the biopsy results. The PSA changes were compared with basal PSA levels and the free/total PSA ratio(f/tPSA). Of the 45 patients who underwent prostate biopsy, histopathology showed prostate cancer in 11, benign prostatic hyperplasia in 33 and prostatic intraepithelial neoplasia in one. Patients with cancer had a significantly greater increase in serum PSA levels during the first week after LHRH injection than those in the benign and control groups. Receiver operating characteristic curves showed that the percentage change in PSA level on day 5 was more diagnostic than total PSA and f/tPSA. There was a marked difference in the PSA response of patients with benign or malignant disease to the testosterone surge produced by the LHRH analogue. Although a larger study would be needed before LHRH-induced provocation could be proposed as a clinical test, in this small series the response was better than that for total PSA or f/tPSA in differentiating benign and malignant disease.

Vomeronasal, olfactory, hormonal convergence in the brain. Cooperation or coincidence?

This paper briefly reviews three topics: (a) Convergent vomeronasal and olfactory chemosensory input into a common circuit considered important for mating in male golden hamsters; (b) Apparent activation of this circuit by intracerebral luteinizing hormone-releasing hormone (LHRH) and (c) Interaction of the LHRH and the two chemosensory inputs. Mapping of c-fos protein in male hamsters mating with females or exposed to female pheromones indicates intense activation in the central vomeronasal pathways, induced by both olfactory and vomeronasal input. This input appears to activate the medial preoptic area, where chemosensory activation is greater in experienced than in inexperienced animals. Intracerebral injection of LHRH facilitates mating behavior and increases Fos expression in the medial preoptic area of mating males. Despite evidence that the release of LHRH in response to female chemosignals is dependent on vomeronasal input, no activation of LHRH neurons has been demonstrated in males exposed to such chemosignals. Electrical stimulation of the vomeronasal organ can induce Fos expression in chemosensory pathways and in medial preoptic LHRH neurons.

Blockage of gonadotropin-induced first ovulation caused by thyroidectomy and its possible mechanisms in rats.

To determine the role of the thyroid gland on the ovarian functions during the initiation process of puberty, we examined the effects and its mechanisms of hypothyroidism on the first ovulation induced by equine chorionic gonadotropin (eCG) in immature female rats. Animals were thyroidectomized on day 22 and were injected with 5 IU of eCG on day 26 to induce the first ovulation on day 29. The number of antral follicles that secrete inhibin and the ovarian weight were significantly increased in thyroidectomized rats (Tx rats) 48 h after eCG treatment compared with those in non-Tx rats. However, thyroidectomy (Tx) significantly suppressed the rates of ovulating animals on day 29. The blockage of ovulation in Tx rats was recovered by administration of human chorionic gonadotropin or luteinizing hormone (LH)-releasing hormone (LHRH) on day 28. Inhibition of serum LH (not follicle-stimulating hormone) levels induced by Tx was almost restored to control levels by injection of LHRH. A significant increment in prolactin levels in Tx rats was also observed on day 28. The present data indicate that Tx before puberty in female rats causes the blockage of the first ovulation and that the inhibitory effects on ovulation are mainly due to the reduction in the preovulatory LH surge, which is partially mediated through an inhibition of LHRH action on the secretion of LH.

Melatonin inhibits naloxone-induced luteinizing hormone release in ovariectomized estrogen-primed rats.

The present study aimed to examine the effect of melatonin on naloxone-induced luteinizing hormone (LH) secretion in ovariectomized estrogen-primed rats. A single intracerebroventricular (i.c.v.) injection of naloxone (mu opioid receptor blocker, 15 micrograms) or an intravenous (i.v.) injection of LH-releasing hormone (LHRH, 50 ng/kg) elicited a transient and significant increase in the serum LH concentration within 10 min. While an i.c.v. injection of 100 ng melatonin by itself did not change the basal LH release, it almost completely inhibited the naloxone-induced LH release. Melatonin (10 ng) also significantly reduced the effect of naloxone. However, an i.c.v. injection of 100 ng melatonin did not affect the LHRH-induced LH release. In separate experiments, the effect of melatonin on naloxone-induced pulsatile LH secretion was studied in estrogen-treated rats. A continuous i.v. infusion of naloxone (20 mg/kg/h) induced LH pulses in rats treated i.c.v. with saline. An i.c.v. administration of 100 ng melatonin, which by itself did not affect basal LH secretion, significantly reduced the frequency, but not the amplitude, of LH pulses induced by the naloxone infusion. These results show that melatonin has a suprapituitary site of action to inhibit naloxone-induced LH release, and suggest that melatonin has an effect in inhibiting the activity of the hypothalamic LHRH pulse generator, either directly or indirectly, in female rats.

Increase in Plasma Luteinizing Hormone and Estradiol-17.BETA. Concentrations following an injection of Luteinizing Hormone-Releasing Hormone in Incubating and Brooding Gifujidori Hens.

Increase in Plasma Luteinizing Hormone and Estradiol-17.BETA. Concentrations following an injection of Luteinizing Hormone-Releasing Hormone in Incubating and Brooding Gifujidori Hens.

Characteristics of luteinizing hormone (LH) and testosterone secretion, pituitary responses to LH-releasing hormone (LHRH), and reproductive function in young bulls receiving the LHRH agonist deslorelin: effect of castration on LH responses to LHRH.

Young bulls were treated with graded dosages of the LHRH agonist deslorelin to ascertain 1) whether increased testosterone secretion persisted over a wide dose range of agonist; 2) whether elevated testosterone was maintained long-term and, if so, what effects there were on reproductive function; and 3) what pituitary responses to exogenous LHRH occurred in intact and castrated bulls receiving deslorelin. In three experiments, bulls received dosages of agonist ranging from approximately 0.15 to 29.0 micrograms deslorelin/kg live weight/day, by means of either bioimplants or injections. At all dosages, deslorelin induced an acute increase in plasma LH concentrations that declined after 24 h but remained at greater concentrations than in controls, although the differences were relatively small. Profiles of LH in bulls treated with deslorelin were characterized by tonic secretion with no clear evidence of LH pulses. Plasma testosterone concentrations were increased at all dosages of deslorelin and in one experiment remained greater than in controls for over 100 days of treatment. This increase was associated with an increase in the rate of testis growth; however, there were no apparent improvements in semen parameters. Bulls receiving deslorelin did not show a typical postcastration rise in plasma LH concentrations, and neither intact nor castrated bulls receiving deslorelin showed an increase in plasma LH after injection of natural sequence LHRH. The absence of endogenous LH pulses and lack of response to exogenous LHRH suggested that the anterior pituitary in bulls receiving LHRH agonist becomes desensitized. However, LH secretion persisted in a tonic manner and was associated with elevated plasma testosterone concentrations. The failure of both intact and castrated bulls receiving deslorelin to respond to exogenous LHRH suggested direct effects of deslorelin on the pituitary, rather than an interaction with steroid feedback.

Luteinizing hormone-releasing hormone is a putative factor that causes LHRH neurons to fire synchronously in ovariectomized rats.

Pulsatile release of luteinizing hormone (LH) is governed by pulsatile release of LH-releasing hormone (LHRH), and each LHRH pulse is produced by synchronized firing of LHRH neurons. However, the mechanism of this synchronized firing is unknown. An increase (volley) in the multiunit activity (MUA), at 20- to 30-min intervals, accompanied by an LH pulse, is found in the median eminence (ME) of ovariectomized rats, suggesting that the MUA reflects the activity of LHRH neurons directly or indirectly. On the hypothesis that LHRH released from LHRH neurons locally in the hypothalamus was involved in the mechanism responsible for the synchronized firings of LHRH neurons, we examined the effect of exogenously administered LHRH on the MUA showing volleys in association with pulsatile LH release in ovariectomized rats. Intravenous injection of LHRH (50 micrograms/kg) evoked a premature volley (average 5.0 min after the injection). Microinjection of LHRH (1 ng) into the ME also evoked a premature volley (average 4.6 min after the injection), accompanied by an LH pulse. Microinjection of LHRH (1 ng) into the medial preoptic area did not cause these effects. The results suggest that LHRH released from LHRH neurons locally in the hypothalamus somehow activates its own and neighboring LHRH neurons, causing synchronized firings of LHRH neurons, and that this mechanism exists at least in and around the ME.

Vomeronasal system, LHRH, and sex behaviour

Vomeronasal chemosensory input is important for male hamster mating behavior, especially in inexperienced animals. Experiments reviewed here showed that intracerebroventricular injection of luteinizing hormone-releasing hormone (LHRH) substantially restores mating behavior impaired by removal of vomeronasal organs in inexperienced hamsters. An analogue molecule Ac 5–10LHRH, which fails to release luteinizing hormone (LH) from the pituitary, has similar behavioural effects. These findings are consistent with the idea that vomeronasal sensory input may trigger intracerebral release of LHRH which then facilitates mating behaviour. Immunocytochemistry for the immediate-early gene-product Fos, used as an indicator of regional brain activation, indicates a selective activation of central vomeronasal pathways during mating behaviour. Chemosensory and other sensory inputs contribute to activation in medial amygdala and bed-nucleus of stria terminalis, but medial preoptic/anterior hypothalamic area activation appears more closely tied to mating behavior itself. Any of these areas may be sites of interaction between vomeronasal chemosensory input and LHRH-containing cells and fibers.