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Gonadotrophin-releasing Hormone (gonadotrophin-releasing + hormone)
Selected AbstractsDiscovery and Evolutionary History of Gonadotrophin-Inhibitory Hormone and Kisspeptin: New Key Neuropeptides Controlling ReproductionJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2010K. Tsutsui Gonadotrophin-releasing hormone (GnRH) is the primary hypothalamic factor responsible for the control of gonadotrophin secretion in vertebrates. However, within the last decade, two other hypothalamic neuropeptides have been found to play key roles in the control of reproductive functions: gonadotrophin-inhibitory hormone (GnIH) and kisspeptin. In 2000, we discovered GnIH in the quail hypothalamus. GnIH inhibits gonadotrophin synthesis and release in birds through actions on GnRH neurones and gonadotrophs, mediated via GPR147. Subsequently, GnIH orthologues were identified in other vertebrate species from fish to humans. As in birds, mammalian and fish GnIH orthologues inhibit gonadotrophin release, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal axis across species. Subsequent to the discovery of GnIH, kisspeptin, encoded by the KiSS-1 gene, was discovered in mammals. By contrast to GnIH, kisspeptin has a direct stimulatory effect on GnRH neurones via GPR54. GPR54 is also expressed in pituitary cells, but whether gonadotrophs are targets for kisspeptin remains unresolved. The KiSS-1 gene is also highly conserved and has been identified in mammals, amphibians and fish. We have recently found a second isoform of KiSS-1, designated KiSS-2, in several vertebrates, but not birds, rodents or primates. In this review, we highlight the discovery, mechanisms of action, and functional significance of these two chief regulators of the reproductive axis. [source] Temporal and Spatial Regulation of CRE Recombinase Expression in Gonadotrophin-Releasing Hormone Neurones in the MouseJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2008A. Wolfe Gonadotrophin-releasing hormone (GnRH) neurones located within the brain are the final neuroendocrine output regulating the reproductive hormone axis. Their small number and scattered distribution in the hypothalamus make them particularly difficult to study in vivo. The Cre/loxP system is a valuable tool to delete genes in specific cells and tissues. We report the production of two mouse lines that express the CRE bacteriophage recombinase in a GnRH-specific manner. The first line, the GnRH-CRE mouse, contains a transgene in which CRE is under the control of the murine GnRH promoter and targets CRE expression specifically to GnRH neurones in the hypothalamus. The second line, the GnRH-CRETeR mouse, uses the same murine GnRH promoter to target CRE expression to GnRH neurones, but is modified to be constitutively repressed by a tetracycline repressor (TetR) expressed from a downstream tetracycline repressor gene engineered within the transgene. GnRH neurone-specific CRE expression can therefore be induced by treatment with doxycycline which relieves repression by TetR. These GnRH-CRE and GnRH-CRETeR mice can be used to study the function of genes expressed specifically in GnRH neurones. The GnRH-CRETeR mouse can be used to study genes that may have distinct roles in reproductive physiology during the various developmental stages. [source] Regulation of Expression of Mammalian Gonadotrophin-Releasing Hormone Receptor GenesJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2005J. P. Hapgood Abstract Gonadotrophin-releasing hormone (GnRH), acting via its cognate GnRH receptor (GnRHR), is the primary regulator of mammalian reproductive function, and hence GnRH analogues are extensively used in the treatment of hormone-dependent diseases, as well as for assisted reproductive techniques. In addition to its established endocrine role in gonadotrophin regulation in the pituitary, evidence is rapidly accumulating to support the expression and functional roles for two forms of GnRHR (GnRHR I and GnRHR II) in multiple and diverse extra-pituitary mammalian tissues and cells. These findings, together with findings indicating that mutations of the GnRHR are linked to the disease hypogonadotrophic hypogonadism and that GnRHRs play a direct role in neuronal migration and reproductive cancers, have presented new therapeutic targets and intensified research into the structure, function and mechanisms of regulation of expression of GnRHR genes. The present review focuses on the current knowledge on tissue-specific and hormonal regulation of transcription of mammalian GnRH receptor genes. Emerging insights, such as the discovery of diverse regulatory mechanisms in pituitary and extra-pituitary cell types, nonclassical mechanisms of steroid regulation, the use of composite elements for cell-specific expression, the increasing profile of hormones involved in regulation, the complexity of kinase pathways that target the GnRHR I gene, as well as species-differences, are highlighted. Although further research is necessary to understand the mechanisms of regulation of expression of GnRHR I and GnRHR II genes, the GnRHR is emerging as a potential target gene for facilitating cross-talk between neuroendocrine, immune and stress-response systems in multiple tissues via autocrine, paracrine and endocrine signalling. [source] The hinge region fragment of immunoglobulin G improves immunogenicity of recombinant gonadotrophin-releasing hormone conjugated to the T-helper epitope in designing peptide vaccinesIMMUNOLOGY, Issue 1pt2 2009Jinshu Xu Summary In our previous study, the hinge fragment (225,232/225,,232,) of human immunoglobulin G1 (IgG1) was used as a space peptide linker for synthesizing the GnRH3,hinge,MVP chimeric peptide, whereby three repeated gonadotrophin-releasing hormone (GnRH) units and a T-cell epitope from measles virus fusion protein (MVP) were amide-bond-linked at the N and C terminus, respectively, to the hinge peptide for producing anti-GnRH antibody responses. To investigate whether or not the hinge region fragment can improve the immunogenicity of GnRH, we further synthesized and purified GnRH3,hinge,MVP, GnRH3,hinge and GnRH3,MVP using recombinant DNA technology. Under high pH conditions, GnRH3,hinge,MVP was capable of forming double-chain structures. Immunization of male mice with the immunogens of GnRH3,hinge,MVP resulted in the generation of high-titre antibodies specific for GnRH. The synthetic GnRH3,hinge and GnRH3,MVP induced a lower titre of anti-GnRH antibody than GnRH3,hinge,MVP. This was followed by a decrease in serum testosterone levels, which resulted in a low level of expression of the relaxin-like factor gene in the testis. Our data suggest that peptide and T-cell epitopes oriented at the N-terminus or C-terminus of hinge peptides simplify the antigenic peptide conjugates and may be considered as potential synthetic immunogens. [source] Recent Discoveries on the Control of Gonadotrophin-Releasing Hormone Neurones in Nonhuman PrimatesJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2010E. Terasawa Since Ernst Knobil proposed the concept of the gonadotrophin-releasing hormone (GnRH) pulse-generator in the monkey hypothalamus three decades ago, we have made significant progress in this research area with cellular and molecular approaches. First, an increase in pulsatile GnRH release triggers the onset of puberty. However, the question of what triggers the pubertal increase in GnRH is still unclear. GnRH neurones are already mature before puberty but GnRH release is suppressed by a tonic GABA inhibition. Our recent work indicates that blocking endogenous GABA inhibition with the GABAA receptor blocker, bicuculline, dramatically increases kisspeptin release, which plays an important role in the pubertal increase in GnRH release. Thus, an interplay between the GABA, kisspeptin, and GnRH neuronal systems appears to trigger puberty. Second, cultured GnRH neurones derived from the olfactory placode of monkey embryos exhibit synchronised intracellular calcium, [Ca2+]i, oscillations and release GnRH in pulses at approximately 60-min intervals after 14 days in vitro (div). During the first 14 div, GnRH neurones undergo maturational changes from no [Ca2+]i oscillations and little GnRH release to the fully functional state. Recent work also shows GnRH mRNA expression increases during in vitro maturation. This mRNA increase coincides with significant demethylation of a CpG island in the GnRH 5,-promoter region. This suggests that epigenetic differentiation occurs during GnRH neuronal maturation. Third, oestradiol causes rapid, direct, excitatory action in GnRH neurones and this action of oestradiol appears to be mediated through a membrane receptor, such as G-protein coupled receptor 30. [source] Kisspeptin and the Preovulatory Gonadotrophin-Releasing Hormone/Luteinising Hormone Surge in the Ewe: Basic Aspects and Potential Applications in the Control of OvulationJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2010A. Caraty The identification of the neural mechanisms controlling ovulation in mammals has long been a ,holy grail' over recent decades, although the recent discovery of the kisspeptin systems has totally changed our views on this subject. Kisspeptin cells are the major link between gonadal steroids and gonadotrophin-releasing hormone (GnRH) neurones. In the female rodent, kisspeptin cells of the preoptic area are involved in the positive-feedback action of oestrogen on GnRH secretion, although the picture appears more complicated in the ewe. As in rodents, activation of preoptic kisspeptin neurones accompanies the GnRH surge in the ewe but an active role for arcuate kisspeptin neurones has also been proposed. Experimentally, kisspeptin is able to restore reproductive function when the hypothalamic-hypophyseal ovarian axis is quiescent. For example, i.v. infusion of a low dose of peptide in anoestrous ewes induces an immediate and sustained release of gonadotrophin, which subsides and then provokes a luteinising hormone (LH) surge a few hours later. This pharmacological intervention induces the same hormonal changes normally observed during the follicular phase of the oestrous cycle, including the secretion of oestrogen and its negative- and positive-feedback actions on the secretion of LH and follicle-stimulating hormone. Accordingly, a high percentage of kisspeptin-infused animals ovulated. Although the multiple facets of how the kisspeptin systems modulate GnRH secretion are not totally understood, the demonstration that exogenous kisspeptin administration can induce ovulation in anovulatory animals paves the way for future therapeutic applications aiming to control reproduction. [source] Projections of RFamide-related Peptide-3 Neurones in the Ovine Hypothalamus, with Special Reference to Regions Regulating Energy Balance and ReproductionJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2009Y. Qi RFamide-related peptide-3 (RFRP-3) is a neuropeptide produced in cells of the paraventricular nucleus and dorsomedial nucleus of the ovine hypothalamus. In the present study, we show that these cells project to cells in regions of the hypothalamus involved in energy balance and reproduction. A retrograde tracer (FluoroGold) was injected into either the arcuate nucleus, the lateral hypothalamic area or the ventromedial nucleus. The distribution and number of retrogradely-labelled RFRP-3 neurones was determined. RFRP-3 neurones projected to the lateral hypothalamic area and, to a lesser degree, to the ventromedial nucleus and the arcuate nucleus. Double-label immunohistochemistry was employed to identify cells receiving putative RFRP-3 input to cells in these target regions. RFRP-3 cells were seen to project to neuropeptide Y and pro-opiomelanocortin neurones in the arcuate nucleus, orexin and melanin-concentrating hormone neurones in the lateral hypothalamic area, as well as orexin cells in the dorsomedial nucleus and corticotrophin-releasing hormone and oxytocin cells in the paraventricular nucleus. Neurones expressing gonadotrophin-releasing hormone in the preoptic area were also seen to receive input from RFRP-3 projections. We conclude that RFRP-3 neurones project to hypothalamic regions and cells involved in regulation of energy balance and reproduction in the ovine brain. [source] KiSS-1 and GPR54 Genes are Co-Expressed in Rat Gonadotrophs and Differentially Regulated In Vivo by Oestradiol and Gonadotrophin-Releasing HormoneJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2008N. Richard Kisspeptin, the product derived from KiSS-1, and its cognate receptor, GPR54, both exert a role in the neuroendocrine control of reproduction by regulating gonadotrophin-releasing hormone (GnRH) secretion. In the present study, we demonstrate, using dual immunofluorescence with specific antibodies, that the KiSS-1 and GPR54 genes are both expressed in rat gonadotrophs. All luteinising hormone ,-immunoreactive (LH,-ir) cells were stained by the KiSS-1 antibody but some kisspeptin-ir cells were not LH, positive; thus, we cannot exclude the possibility that kisspeptins are expressed in other pituitary cells. All GPR54-ir are co-localised with LH, cells, but only a subset of LH, cells are stained with the GPR54 antibody. Using the real-time reverse transcription-polymerase chain reaction (RT-PCR), we found that the expression of KiSS-1 and GPR54 is differentially regulated by steroids. In the female, KiSS-1 mRNA levels dramatically decreased following ovariectomy (OVX), and this decrease was prevented by administration of 17,-oestradiol (E2), but not by administration of GnRH antagonist or agonist. Administration of E2 in OVX rats receiving either GnRH antagonist or agonist clearly shows that E2 acts directly on the pituitary to positively control KiSS-1 expression. In OVX rats, administration of the selective oestrogen receptor (ER), ligand propylpyrazoletriol, but not the selective ER, ligand diarylpropionitrile, mimics this effect. By contrast, our study shows that GPR54 expression is positively regulated by GnRH and negatively controlled by chronic exposure to E2. In summary, our data document for the first time that, in the female rat pituitary, KiSS-1 expression is up-regulated by oestradiol, similarly to that seen in the anteroventral periventricular nucleus of the hypothalamus. Conversely, GPR54 is up-regulated by GnRH, which exclusively targets gonadotrophs. [source] Elevated KiSS-1 Expression in the Arcuate Nucleus Prior to the Cyclic Preovulatory Gonadotrophin-Releasing Hormone/Lutenising Hormone Surge in the Ewe Suggests a Stimulatory Role for Kisspeptin in Oestrogen-Positive FeedbackJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2006K. M. Estrada Kisspeptins are encoded by the gene KiSS-1 and regulate gonadotrophin-releasing hormone (GnRH) and gonadotrophin secretion in various species, including humans. Here, we quantify gene expression of KiSS-1 in the arcuate nucleus (ARC) across the ovine oestrous cycle and demonstrate an increase in the caudal division of the ARC during the preovulatory period. These data strongly suggest that kisspeptins are involved in the generation of the preovulatory GnRH and luteinising hormone surge. [source] Reproduction Phase-Related Expression of ,-Endorphin-Like Immunoreactivity in the Nucleus Lateralis Tuberis of the Female Indian Major Carp Cirrhinus mrigala: Correlation with the Luteinising Hormone Cells-Ovary AxisJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2006A. J. Sakharkar Abstract The present study aimed to determine whether ,-endorphin immunoreactivity (bEP-ir) in the neurones of the nucleus lateralis tuberis (NLT) is linked to the seasonal cycle and shows correlation with the number of luteinising hormone (LH) cells in the pituitary gland and ovaries in the teleost, Cirrhinus mrigala. Although LH cells were moderately immunostained during the resting phase (December to January), the morphological profile suggested increased synthetic and secretory activity during the preparatory (February to April) and prespawning (May to June) phases. However, LH immunoreactivity was greatly reduced (P < 0.001) in the spawning (July to August) phase, suggesting massive discharge of the hormone; this pool was partly replenished in the postspawning (September to November) phase. The ovaries grew rapidly in the preparatory and prespawning phases; maximal size was attained during spawning, when ovulation occurred. Thereafter, the ovaries regressed. The NLT of C. mrigala is divisible into the pars lateralis (NLTl) and medialis (NLTm). During the postspawning and resting phases, bEP-ir was readily detectable in the NLTm as well as NLTl neurones. However, a steady reduction in the immunoreactivity was observed in the NLTm neurones during the preparatory through spawning phases (P < 0.001), suggesting a negative correlation with the LH cells-ovary axis. Thus, the inhibitory influence of ,-endorphin on the gonadotrophin-releasing hormone (GnRH)-LH axis appears to be attenuated during the preparatory through spawning phases. This may be necessary for the rapid stimulation of the axis culminating in spawning. Neurones of the NLTl also showed a gradual reduction in bEP-ir during the preparatory and prespawning phases (P < 0.01) and may therefore play a similar role. However, significant augmentation of the immunoreactivity was noticed in these neurones during the spawning phase (P < 0.001), the physiological significance of which is unknown. Although the present study demonstrated a temporal correlation between the ,-endorphin in the NLT, LH cells and the ovary, we suggest that the peptide in the NLTl and NLTm may show functional duality during the spawning phase. [source] Evidence for a Stimulatory Action of Melanin-Concentrating Hormone on Luteinising Hormone Release Involving MCH1 and Melanocortin-5 ReceptorsJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2006J. F. Murray Abstract The present series of studies aimed to further our understanding of the role of melanin-concentrating hormone (MCH) neurones in the central regulation of luteinising hormone (LH) release in the female rat. LH release was stimulated when MCH was injected bilaterally into the rostral preoptic area (rPOA) or medial preoptic area (mPOA), but not when injected into the zona incerta (ZI), of oestrogen-primed ovariectomised rats. In rats that were steroid-primed to generate a surge-like release of LH, MCH administration into the ZI blocked this rise in LH release: no such effect occurred when MCH was injected into the rPOA or mPOA. In vitro, MCH stimulated gonadotrophin-releasing hormone (GnRH) release from hypothalamic explants. Double-label immunohistochemistry showed GnRH-immunoreactive neurones in the vicinity of and intermingled with immunoreactive MCH processes. MCH is the endogenous ligand of the MCH type 1 receptor (MCH1-R). Previously, we have shown a role for melanocortin-5 receptors (MC5-R) in the stimulatory action of MCH, so we next investigated the involvement of both MCH1-R and/or MC5-R in mediating the actions of MCH on GnRH and hence LH release. The stimulatory action of MCH in the rPOA was inhibited by administration of antagonists for either MCH1-R or MC5-R. However, in the mPOA, the action of MCH was blocked only by the MC5-R antagonist. LH release was stimulated by an agonist for MC5-R injected into the rPOA or mPOA; this was blocked by the MC5-R antagonist but not the MCH1-R antagonist. These results indicate that both MCH1-R and MC5-R are involved in the central control of LH release by MCH. [source] Expression of AMPA Receptor Subunits (GluR1,GluR4) in Gonadotrophin-Releasing Hormone Neurones of Young and Middle-Aged Persistently Oestrous Rats During the Steroid-Induced Luteinising Hormone SurgeJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2006J. D. Bailey Abstract Glutamate provides excitatory input to gonadotrophin-releasing hormone (GnRH) neurones and elicits a response indicative of AMPA receptors. To determine if and which AMPA subunits are expressed by GnRH neurones, we conducted triple-label immunohistochemistry and confocal analyses on tissue obtained at 08.00, 12.00, 16.00 and 20.00 h from young and middle-aged, persistently oestrous (MA-PE) rats that were ovariectomised and primed with oestrogen and progesterone to induce a luteinising hormone (LH) surge. Each AMPA subunit was found in GnRH neurones, but in different patterns across the diurnal cycle, which were influenced by age. GluR1 expression increased earlier in young rats and the percentage of Fos-positive GnRH neurones expressing GluR1 rose significantly and was sustained from 12.00,16.00 h. GluR1 expression was delayed in MA-PE rats and the percentage of Fos-positive GnRH neurones expressing GluR1 peaked at 20.00 h. GluR2 expression in GnRH neurones did not change over time and was not affected by age; however, the percentage of Fos-positive GnRH neurones expressing GluR2 increased earlier and was sustained from 08.00,16.00 h in young rats whereas, in MA-PE rats, this percentage peaked at 20.00 h. GluR3 expression also increased earlier in young rats and peaked at 12.00 h but was delayed in MA-PE rats and peaked at 20.00 h. The number of Fos-positive GnRH neurones that coexpressed GluR3 peaked at 12.00 h in young rats but showed little change from 12.00,20.00 h in MA-PE rats. GluR4 expression was maintained at higher levels at 08.00 and 12.00 h in young rats; although the percentage of Fos-positive GnRH neurones expressing GluR4 peaked at 12.00 h in young rats, it showed little change in MA-PE rats. In summary, our data show that a higher proportion of Fos-positive GnRH neurones coexpressed AMPA receptor subunits in young rats and the expression, particularly of GluR1 and GluR2, was increased and sustained throughout the surge, whereas GluR3 and GluR4 expression peaked just before. In MA-PE rats, the rate of expression of GluR subunits and Fos in GnRH neurones was altered in a manner that may explain the delay and attenuation of the LH surge. [source] Effect of Calcitonin Gene-Related Peptide on Gonadotrophin-Releasing Hormone mRNA Expression in GT1-7 CellsJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2005J. S. Kinsey-Jones Abstract Recent evidence has shown calcitonin gene-related peptide (CGRP) to be a key mediator of stress-induced suppression of the gonadotrophin-releasing hormone (GnRH) pulse generator, although little is known about the neural pathways involved. In the present study, we investigated the potential direct action of CGRP on GnRH neurones using GT1-7 cells, an established GnRH cell line. First, we detected expression of the CGRP receptor subunits, calcitonin receptor-like receptor and receptor activity-modifying protein-1 in the GT1-7 cells by reverse transcriptase-polymerase chain reaction. Second, we have shown that CGRP inhibits GnRH mRNA expression in the GT1-7 cells, which was effectively reversed by the CGRP receptor antagonist, CGRP8-37. These results suggest that CGRP down regulates expression of GnRH mRNA, via CGRP receptors in the GT1-7 cell, thus implying that a potential direct action of CGRP may mediate a suppressive effect on the GnRH neural network. [source] Central GABAA but not GABAB Receptors Mediate Suppressive Effects of Caudal Hindbrain Glucoprivation on the Luteinizing Hormone Surge in Steroid-Primed, Ovariectomized Female RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2005S. R. Singh Abstract The neurochemical mechanisms that link caudal hindbrain glucoprivic-,sensitive' neurones with the forebrain gonadotrophin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) axis remain unclear. Available studies indicate that the amino acid neurotransmitter, ,-aminobutyric acid (GABA), inhibits reproductive neuroendocrine function, and that caudal fourth ventricular administration of the glucose antimetabolite, 5-thioglucose (5TG), enhances GABA turnover within discrete septopreoptic structures that regulate LH secretion. The current experiments utilized the selective GABAA and GABAB receptor antagonists, bicuculline and phaclofen, as pharmacological tools to investigate whether one or both receptor subtypes function within neural pathways that suppress GnRH neuronal transcriptional activation and LH release during central glucose deficiency. During the ascending phase of the afternoon LH surge, groups of steroid-primed, ovariectomized female Sprague-Dawley rats were pretreated by lateral ventricular administration of bicuculline, phaclofen, or vehicle only, before fourth ventricular injection of 5TG or vehicle. The data indicate that, 2 h after 5TG treatment, Fos immunoexpression by rostral preoptic GnRH neurones and plasma LH levels were diminished relative to the vehicle-treated controls, and that inhibitory effects of 5TG on these parameters were attenuated by pretreatment with bicuculline, but not phaclofen. These results demonstrate that central GABAA, but not GABAB receptor stimulation during hindbrain glucoprivation, is required for maximal inhibition of reproductive neuroendocrine function by this metabolic challenge. The current studies thus reinforce the view that central GABAergic neurotransmission mediates regulatory effects of central glucoprivic signalling on the GnRH-pituitary LH axis. [source] Characterization of Gonadotrophin-Releasing Hormone Precursor cDNA in the Old World Mole-Rat Cryptomys Hottentotus Pretoriae: High Degree of Identity with the New World Guinea Pig SequenceJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2005T. Kalamatianos Abstract Regulation of pituitary gonadotrophins by the decapeptide gonadotrophin-releasing hormone 1 (GnRH1) is crucial for the development and maintenance of reproductive functions. A common amino acid sequence for this decapeptide, designated as ,mammalian' GnRH, has been identified in all mammals thus far investigated with the exception of the guinea pig, in which there are two amino acid substitutions. Among hystricognath rodents, the members of the family Bathyergidae regulate reproduction in response to diverse cues. Thus, highveld mole-rats (Cryptomys hottentotus pretoriae) are social bathyergids in which breeding is restricted to a particular season in the dominant female, but continuously suppressed in subordinate colony members. Elucidation of reproductive control in these animals will be facilitated by characterization of their GnRH1 gene. A partial sequence of GnRH1 precursor cDNA was isolated and characterized. Comparative analysis revealed the highest degree of identity (86%) to guinea pig GnRH1 precursor mRNA. Nevertheless, the deduced amino acid sequence of the mole-rat decapeptide is identical to the ,mammalian' sequence rather than that of guinea pigs. Successful detection of GnRH1-synthesizing neurones using either a guinea pig GnRH1 riboprobe or an antibody against the ,mammalian' decapeptide is consistent with the guinea pig-like sequence for the precursor and the classic ,mammalian' form for the decapeptide. The high degree of identity in the GnRH1 precursor sequence between this Old World mole-rat and the New World guinea pig is consistent with the theory that caviomorphs and phiomorphs originated from a common ancestral line in the Palaeocene to mid Eocene, some 63,45 million years ago. [source] Rainfall, dispersal and reproductive inhibition in eusocial Damaraland mole-rats (Cryptomys damarensis)JOURNAL OF ZOOLOGY, Issue 4 2002A. J. Molteno Abstract Non-reproductive female Damaraland mole-rats Cryptomys damarensis that were caught before a period of good rainfall (during which 90% of the average annual fell) (Group 1), exhibited a significantly lower pituitary sensitivity to gonadotrophin-releasing hormone compared to non-reproductive females (Group 2) caught in the same area, close to the end of the wet period. Group 2 were also significantly heavier than Group 1. Pituitary sensitivity was not significantly correlated to body mass within either group of females, nor within groups of reproductive males and non-reproductive males from a laboratory held colony. This suggests that rainfall may have resulted in the simultaneous, but unrelated, increase in pituitary sensitivity and body mass. Larger size and reduced sexual inhibition assist dispersal and the probability of successful independent reproduction, during periods when environmental constraints on dispersal are relaxed. These findings support the hypothesis that low rainfall may be an important constraint on dispersal and an important factor promoting the evolution of reproductive inhibition, and consequently eusociality, in this species. [source] Sperm binding to the human zona pellucida and calcium influx in response to GnRH and progesteroneANDROLOGIA, Issue 5 2002P. Morales Summary. In this study the effect of the sequential exposure of spermatozoa to progesterone and gonadotrophin-releasing hormone (GnRH) upon zona binding and the intracellular free Ca2+ concentration was evaluated. Sperm aliquots were treated as follows: (a) 0.7 ,mol 1,1 progesterone or 0.1% DMSO (progesterone solvent) followed by 50 nmol 1,1 of GnRH; (b) 50 nmol 1,1 of GnRH or distilled water (GnRH solvent) followed by 0.7 ,mol 1,1 of progesterone. Additional aliquots were incubated with DMSO or distilled water (controls) and with 0.7 ,mol 1,1 of progesterone or 50 nmol 1,1 of GnRH. All treatments were for 5 min. Motile spermatozoa were incubated in modified Tyrode's medium, at 37 °, 5% CO2, 10times106 spermatozoa ml,1, for 4.5 h. Intracellular Ca2+ concentration and sperm-zona binding was evaluated using fura 2 and the hemizona assay, respectively. GnRH and progesterone increased sperm-zona binding and the Ca2+ concentration. Regarding zona binding, the effect of GnRH was significantly greater when the spermatozoa had been previously treated with progesterone (progesterone , GnRH = 185 ± 116 zona-bound spermatozoa versus DMSO , GnRH = 99 ± 15, P <0.001). On the other hand, previous treatment with GnRH did not modify their subsequent response to progesterone (GnRH , progesterone = 114 ±19 zona-bound spermatozoa versus distilled water , progesterone = 108 ± 22, NS). The results regarding intracellular Ca2+ showed a similar pattern. These findings suggest a priming effect of progesterone upon a GnRH-induced increase in sperm-zona binding and intracellular Ca2+. [source] Oestrogen deficiency causes DNA damage in uterine leiomyoma cells: a possible mechanism for shrinkage of fibroids by GnRH agonistsBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 1 2001Ya-Min Cheng Objective To examine whether gonadotrophin-releasing hormone agonist or oestradiol can directly affect DNA in leiomyoma cells. Design In vitro explant culture of leiomyoma cells. Setting University research group. Sample Leiomyoma cells were cultured from the specimens of four premenopausal women at myomectomy. Methods The presence of gonadotrophin-releasing hormone receptor in leiomyoma cells was determined by reverse transcriptase,olymerase chain reaction. Leiomyoma cells were treated with gonadotrophin-releasing hormone agonist or cultured in different concentrations of oestrogen, progesterone or fetal calf serum for one, four or seven days. Main outcome measures Cell number, expression of proliferating cell nuclear antigen, and DNA damage after one, four or seven days of treatment. Results Gonadotrophin-releasing hormone receptor messenger ribonucleic acid was detected on cultured leiomyoma cells. Leiomyoma cell growth was not affected by the addition of gonadotrophin-releasing hormone agonist or progesterone, but increased with oestrogen or fetal calf serum supplementation. Overexpression of proliferating cell nuclear antigen was prevented in cultures added with oestrogen or fetal calf serum, but not related to gonadotrophin-releasing hormone agonist treatment. Significant decreases in DNA damage as indicated by decreased comet number were found in the leiomyoma cultures treated with oestrogen or fetal calf serum for four and seven days but not with gonadotrophin-releasing hormone agonist or progesterone. Furthermore, 5% fetal calf serum supplementation was more growth supporting and more significantly reduced the comet number than 250 pM 17 , -oestradiol. Conclusion Cell growth, proliferating cell nuclear antigen expression and DNA damage are dependent on oestrogen or fetal calf serum, but independent of gonadotrophin-releasing hormone agonist or progesterone. Our findings suggest that gonadotrophin-releasing hormone agonist-induced leiomyoma shrinkage may be due in part to a mechanism involving DNA damage, and support the hypothesis that gonadotrophin-releasing hormone agonist exerts its action indirectly through oestrogen action on the tumour level. [source] Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancerBJU INTERNATIONAL, Issue 11 2009Roger S. Kirby Hormonal therapy is the main recommended treatment for locally advanced and metastatic prostate cancer. Luteinizing hormone-releasing hormone (LHRH) agonists, such as buserelin, goserelin, leuprorelin and triptorelin, stimulate the pituitary's gonadotrophin-releasing hormone (GnRH) receptor, ultimately leading to its de-sensitization and subsequent reduction of LH and testosterone levels. However, this reduction is accompanied by a well described increase or ,surge' in LH and testosterone levels, necessitating the concomitant administration of an antiandrogen to combat the potential effects of transient acceleration in cancer activity. Two pure GnRH antagonists have been developed, abarelix and degarelix, that are devoid of any agonist effect on the GnRH receptor and consequently do not result in testosterone flare. Abarelix was the first GnRH antagonist to be developed and was approved by the USA Food and Drug Administration in 2004 for the initiation of hormonal castration in advanced or metastasizing hormone-dependent prostate carcinoma, when rapid androgen suppression is necessary. Clinical data on both abarelix and degarelix show that they can produce rapid and sustained decreases in testosterone to castrate levels without the need for co-administration of an antiandrogen, and with a very low complication rate in the short term. [source] Final height after combined growth hormone and GnRH analogue treatment in adopted girls with early pubertyACTA PAEDIATRICA, Issue 11 2004T Tuvemo Background: Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin-releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent. Aim: To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty. Methods: Forty-six girls with early or precocious puberty (age ± 9.5y) adopted from developing countries were randomized for treatment for 2,4 y with GnRH analogue, or with a combination of GH and GnRH analogue. Results: During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue-treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below ,2 standard deviation scores (SDS). Conclusion: The difference between the two groups is statistically significant, and possibly of clinical importance. A future challenge is to identify a subgroup with clinically significant advantage of GH addition to GnRH analogue treatment. Being very short on arrival in Sweden and being short and young at start of treatment are possible indicators. [source] | ||||||||||