Transcriptomic evidence of luteinizing hormone-releasing hormone agonist (LHRH-A) regulation on lipid metabolism in grass carp (Ctenopharyngodon idella).

In this study, RNA sequencing was used to identify the hepatic gene expression profile in grass carp associated with luteinizing hormone-releasing hormone agonist (LHRH-A) treatment. A total of 93,912,172 reads were generated by HiSeq 4000 sequencing platform. After filtering, 83,450,860 clean reads were mapped to the reference genome. By calculating the FPKM of genes, 1475 differentially expressed genes were identified. PPAR signaling pathway was enriched with upregulated genes in LHRH-A injection group showing the regulation of the lipid metabolism by LHRH-A. The expression of eight key genes in PPAR signaling pathway was confirmed by qPCR and the results suggested that ACSL4A, ACSL4B, ANGPTL4, LPL, RXRBA and SLC27A1B were significantly stimulated by LHRH-A injection. This investigation provides the evidence that LHRH-A could play a role in lipid metabolism.

Transcriptome analysis of common carp (Cyprinus carpio) provides insights into the ovarian maturation related genes and pathways in response to LHRH-A and dopamine inhibitors induction.

Luteinizing hormone-releasing hormone analog (LHRH-A) and dopamine inhibitors have been widely used to induce oocyte maturation and ovulation in domesticated fishes. Although this approach represents a reliable method for regulating fish reproduction, the underlying molecular mechanisms mediating LH action are largely unexplored. The objective of this study was to determine the transcriptional profile of gene programming in hormone-treated common carp. In the present study, female common carp were intraperitoneally injected with LHRH-A together with dopamine inhibitors, and control fish were injected with saline. Ovarian morphological changes were analysed by both light microscopy and scanning electron microscopy. Furthermore, gene expression profiling of the brain and ovarian tissues was performed by Illumina sequencing. Compared to the control carp, hormone treatment resulted in morphological changes including disappearance of nuclear membrane, breakdown of germinal vesicle (GVBD), and fusion of yolk globules, reflecting that hormones significantly promoted oocyte maturation. In comparison to control, we have identified 867 and 9,053 differentially expressed genes in the hormone-treated female brain and ovary, respectively. In the brain, most of the identified genes were significantly enriched in 18 KEGG pathways. In the ovarian tissue, the identified genes were significantly involved in 9 pathways. In the hormone-treated carp, genes were involved in calcium signalling pathway, cAMP signalling pathway, insulin secretion, and oxidative phosphorylation pathway, which showed obvious associations with ovarian maturation. The present study provides transcriptomic information for hormone-treated carp, which might be useful for studying the endocrine regulation and mechanisms of ovarian maturation in domesticated fishes.

Neuromodulatory effects of GnRH on the caudal neurosecretory Dahlgren cells in female olive flounder.

Gonadotropin-releasing hormone (GnRH) is considered a key player in reproduction. The caudal neurosecretory system (CNSS) is a unique neurosecretory structure of fish that may be involved in osmoregulation, nutrition, reproduction, and stress-related responses. However, a direct effect of GnRH on Dahlgren cells remains underexplored. Here, we examined the electrophysiological response of Dahlgren cell population of the CNSS to GnRH analog LHRH-A2 and the transcription of related key genes of CNSS. We found that GnRH increased overall firing frequency and may be changed the firing pattern from silent to burst or phasic firing in a subpopulation of Dahlgren cells. The effect of GnRH on a subpopulation of Dahlgren cells firing activity was blocked by the GnRH receptor (GnRH-R) antagonist cetrorelix. A positive correlation was observed between the UII and GnRH-R mRNA levels in CNSS or gonadosomatic index (GSI) during the breeding season. These findings are the first demonstration of the ability of GnRH acts as a modulator within the CNSS and add to our understanding of the physiological role of the CNSS in reproduction and seasonal adaptation.

A review of clinical evidence to assess differences in efficacy and safety of luteinizing hormone-releasing hormone (LHRH) agonist (goserelin) and LHRH antagonist (degarelix).

Luteinizing hormone-releasing hormone agonist (LHRH-A), goserelin, and antagonist, degarelix, are both indicated for the treatment of advanced prostate cancer (PCa); however, large comparative trials evaluating their efficacy and safety are lacking. In this review, we assessed the available evidence for both the drugs. Although degarelix achieves an early rapid decline in testosterone (T) and prostate-specific antigen (PSA) levels, median T and PSA levels, in addition to prostate volume and International Prostate Symptom Scores, become comparable with goserelin over the remaining treatment period. Degarelix causes no initial flare, therefore it is recommended in patients with spinal metastases or ureteric obstruction. Goserelin achieves lower PSA, improved time to progression, and better survival outcomes when administered adjunctively to radiotherapy compared with radiotherapy alone, with significant results even over long-term follow-up. The evidence supporting adjuvant degarelix use is limited. Goserelin has better injection site safety, single-step delivery, and an efficient administration schedule compared with degarelix, which has significantly higher injection site reactions and less efficient administration mechanism. There is conflicting evidence about the risk of cardiovascular disease (CVD), and caution is required when using LHRH-A in patients with preexisting CVD. There is considerable long-term evidence for goserelin in patients with advanced PCa, with degarelix being a more recent option. The available comparative evidence of goserelin versus degarelix has several inherent limitations related to study design, sample size, conduct, and statistical analyses, and hence warrants robust prospective trials and long-term follow-up.

Comparison of the effects of Origanum vulgare with LHRH-A2 and 17ß-estradiol on the ultrastructure of gonadotroph cells and ovarian oogenesis in immature Trichogaster trichopterus.

Origanum vulgare is a plant of the mint family that contains phytoestrogens. This study compared the effects of O. vulgare, LHRH-A2, and 17ß-estradiol on the ultrastructure of gonadotroph cells and ovarian oogenesis in immature Trichogaster trichopterus. Fish (5.1±0.032cm and 2.1±0.043g, n=150) were randomly divided into four treatment groups (three hormonal treatments and control) and treated intramuscularly at four levels with 17ß-estradiol or O. vulgare at 10, 20, 30 and 50mg/kg body weight and with LHRH-A2 at 0.001, 0.002, 0.003, and 0.005mg/kg body weight. There were three control treatments: saline, ethanol and placebo. Fish were kept in 15 tanks, with 10 fish per tank, injected a total of seven doses over 13 days. Gonadosomatic index (GSI) and oocyte diameter were lower (P≤0.05) in the control than in the three hormonal treatments. The highest GSI and oocyte diameter responses were observed in fish treated with 17ß-estradiol (2.76±0.23%, 149.8±15.43mm) followed by O. vulgare (1.86±0.18%, 104.3±11.5mm) and LHRH-A2 (1.52±0.12%, 91.75±9.02mm) (P≤0.05). Moreover, there was a significant effect of dose level within all the hormonal treatments (P≤0.05). The effect of treatment on the length and weight was likely GSI. Ovarian tissue results showed faster oogenesis of oocytes in fish treated with O. vulgare, after 17ß-estradiol. Ultrastructure of gonadotroph cells demonstrated less stimulation by O. vulgare than by 17ß-estradiol and LHRH-A2. This study suggests that compared with the two hormonal treatments, O. vulgare dose-dependently affects ovarian oogenesis and gonadotroph cells.

THE MORPHOMETRIC ANALYSIS OF PITUITARY GONADOTROPIC CELLS IN THE PREGNANT RATS AFTER BEING INJECTED BY A HIGH DOSE OF LUTEINIZING HORMONE RELEA-SING HORMONE ANALOGUE (LHRH-A) / 解剖学报

The specific anti-rat LH in the peroxidase anti-peroxidase (PAP) immunohistochemical method was used to demonstrate the pituitary gonadotropic cells in the pregnant rats, and then the morphometric analysis method was used to study the change of the number, size and nucleo-cytoplasmic ratio parameters of the gonadotropic cells in pregnant rats after being injected by a high dose of LHRH-A.It was observed that on 24h after injection the number of gonadotropic cells decreased, their size became smaller and their nucleo-cytoplasmic ratio larger: the cell number per mm~3 pituitary tissue was from (4.25?0.21)?10~4 to (2.49?0.14)?10~4; the cell size from 1295?35?m~3 to 895?31?m~3; the nucleo-cytoplasmic ratio from 0.144?0.005 to 0.229?0.010. On 48h after injection these changes were in the process of recovery. On 168h after injection all parameters were recovered.Our observations suggest that after being injected by a high dose of LHRH-A the change of gonadotropic cells in pregnant rats results from the exogenous high dose of LHRH-A which has stimulated gonadotropic cells to release a great amount of LH. It is believed, however, that the changes of gonadotropic cells caused by a high dose of LHRH-A can still return to normal.

LHRH-A for treating prostatic cancer with the occurrence of metastasis after castration (report of 9 cases) / 中华泌尿外科杂志

Objective To evaluate the use of LHRH A for treating prostatic cancer with the occurrence of metastasis or recurrence after castration. Methods LHRH A has been instituted to 9 cases of pathologically verified prostatic cancer with the occurrence of metastasis or recurrence after castration.The therapeutic results were studied. Results Ideal improvement was noted in 4 with all the parameters turned normal.These 4 patients have survived well for 7,3,2 and 1 year respectively.Marked improvement occurred in 2 with part of the parameters turned normal or markedly improved shortly after the treatment.The condition of 1 patient became stable with drop of blood PSA and shrinkage of the prostatic mass.In 3 patients,the metastatic lesion became stable.with the use of LHRH A,the penis became markedly atrophic. Conclusions LHRH A is markedly effective in most cases of prostatic cancer with the occurrence of metastasis or recurrence after castration.The therapeutic efficacy depends on the sensitivity of the prostate cancer cells to the drug.Drug resistance may issue as time goes by.