Disease relevance of Gnrh1

• GnRH also stimulates cAMP production but at high concentrations has a pertussis toxin-sensitive inhibitory effect, indicative of receptor coupling to G(i) [1].
• We examined changes in GnRH and NMDA-R1 gene expression by RNase protection assay of preoptic area-anterior hypothalamic (POA-AH) dissections of female rats undergoing normal puberty or in which precocious puberty was induced by treatment with the glutamate agonist NMA [2].
• This suggests that hyperprolactinemia inhibits GnRH-R responses to GnRH in females by a direct action on the pituitary gonadotroph [3].
• After these GnRH injections, all rats received 6.6 micrograms GnRH, sc, 1 h before decapitation to determine acute LH and FSH responses [3].
• Gonadotropin-releasing hormone (GnRH) receptor mutants from patients with hypogonadotropic hypogonadism are frequently misrouted proteins that exert a dominant-negative (DN) effect on human (h) wild-type (WT) receptor, due to oligomerization and retention in the endoplasmic reticulum [4].

Psychiatry related information on Gnrh1

• Modulation of gonadotropin secretion at the pituitary level by testosterone in gonadotropin-releasing hormone-treated male rats during food deprivation [5].
• The lack of experimental psychopharmacological data prompted us to investigate the effects of GnRH on the 'learned helplessness' behavioral model of depression in rats [6].
• Gonadotropin-releasing hormone agonist therapy decreased PA and MMP activities and also increased PAI and MMPI activities [7].
• Fos-like IR was found within a significant number of GnRH-positive neurons in the anterior preoptic area caudal to the organum vasculosum following copulation with intromission or vaginocervical stimulation as compared with no stimulation [8].
• Neuropeptide Y (NPY) displays diverse modes of action in the CNS including the modulation of feeding behavior, gonadotropin releasing hormone release, and stress responses [9].

High impact information on Gnrh1

• Immunocytochemical localization in rat brain of a prolactin release-inhibiting sequence of gonadotropin-releasing hormone prohormone [10].
• The cloned complementary DNA sequence encoding the human gonadotropin-releasing hormone (GnRH) precursor protein was used to construct an expression vector for the bacterial synthesis of the 56-amino acid GnRH-associated peptide (GAP) [11].
• We report here that a substance recognized by this antibody is present in GnRH-containing neurones of the rat brain and appears to coexist with GnRH in secretory granules of nerve terminals in the median eminence [10].
• Inhibition of dopamine biosynthesis by gonadotropin-releasing hormone in rat [12].
• The data indicate that GnRH stimulates redistribution of calmodulin from the cytosol to the plasma membrane and suggest that the molecule may have a role in the mechanism of stimulus-secretion coupling [13].

Chemical compound and disease context of Gnrh1

• Pituitary gonadotropin-releasing hormone (GnRH) receptor responses to GnRH in hypothalamus-lesioned rats: inhibition of responses by hyperprolactinemia and evidence that testosterone and estradiol modulate gonadotropin secretion at postreceptor sites [3].
• The regression of experimental and clinical pancreatic cancers by treatment with gonadotropin-releasing hormone (GnRH) agonists or antagonists has been repeatedly reported and is usually presumed to result from the creation of a sex steroid deficiency [14].
• To verify puberty-inhibiting effects of GnRH analogues, we used 26-d-old female rats with androgen-induced precocious puberty after injecting subcutaneously single 300 microg danazol on postnatal d 5 [15].
• In this patient, the occurrence of precocious puberty was thought to result from excessive stimulation by glycine of the NMDA receptors linked to the GnRH neurons [16].
• The repression of GnRH mRNA levels appears to occur at the transcriptional level, as simian virus 40 T antigen mRNA expression, which is under the control of 2.3 kb of the rat GnRH 5'-regulatory region, mimics the down-regulation of GnRH after treatment with estradiol [17].

Biological context of Gnrh1

• A mechanism for the differential regulation of gonadotropin subunit gene expression by gonadotropin-releasing hormone [18].
• These cells, when cotransfected with regulatory regions of the common alpha, LH beta, or FSH beta subunit gene fused to a luciferase reporter gene, respond to GnRH with an increase in luciferase activity [18].
• Restricted expression of the rat GnRH gene is driven by a multicomponent enhancer and an evolutionarily conserved promoter [19].
• Furthermore, we have shown that DNA sequences at -490/-352 confer GnRH responsiveness to the rat LHbeta gene [20].
• Gonadotropin-releasing hormone neurons, NMDA receptors, and their regulation by steroid hormones across the reproductive life cycle [21].

Anatomical context of Gnrh1

• Previous studies have been limited by lack of available cell lines that express the LH and FSH subunit genes and respond to GnRH [18].
• This increase is attributable, at least in part, to activation of the GnRH neurosecretory system by inputs from neurotransmitters, such as glutamate, acting via NMDA receptors [2].
• Expression of the GnRH gene is confined to a rare population of neurons scattered throughout the hypothalamus [19].
• Regulation of progestin biosynthetic enzymes in cultured rat granulosa cells: effects of prolactin, beta 2-adrenergic agonist, human chorionic gonadotropin and gonadotropin releasing hormone [22].
• The amounts of GnRH and GnRHR mRNA were measured in the preoptic area (POA) and posterior mediobasal hypothalamus (pMBH) micropunch samples from individual rat brain slices by respective competitive reverse transcription-polymerase chain reactions [23].

Associations of Gnrh1 with chemical compounds

• The hypothalamic hormone gonadotropin-releasing hormone (GnRH) is released in a pulsatile fashion, with its frequency varying throughout the reproductive cycle [18].
• This autocrine mechanism could serve as a timer to determine the frequency of pulsatile GnRH release by regulating Ca(2+)- and cAMP-dependent signaling and GnRH neuronal firing [1].
• Messenger RNA and protein levels of GnRH and NMDAR subunits were measured in neuroendocrine brain regions in response to estrogen treatment, or across the reproductive cycle [21].
• In addition to their regulation by sex steroids, GnRH neurons are affected by inputs from neurotransmitters such as glutamate, acting via the NMDA receptor (NMDAR) [21].
• Castrate male rats received testosterone implants (cast + T) to inhibit endogenous GnRH secretion [24].

Physical interactions of Gnrh1

• Pituitary GnRH-receptor content was assessed by the evaluation of saturation binding of a GnRH analog, [125I]-D-Ala6-des-Gly10-GnRH, to pituitary membrane preparations [25].
• In the in vivo study gonadotropin-releasing hormone binding sites and rat luteinizing hormone beta-messenger ribonucleic acid in the pituitary decreased during gonadotropin-releasing hormone agonist treatment, but serum levels of rat luteinizing hormone did not decrease [26].
• Neither GnRH nor GnRH-A affected the binding affinity (Kd) of ovarian LH receptor [27].
• A growing body of evidence suggests a role for guanyl nucleotide binding proteins (G proteins) in GnRH action [28].

Regulatory relationships of Gnrh1

• In contrast, in 3-day fasted rats leptin was effective in stimulating the secretion of GnRH, alpha-MSH, and LH, regardless of the site of perfusion [29].
• TX reduced basal and stimulated LH secretion, increased PRL secretion and induced a robust GnRH self-priming [30].
• Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y [31].
• In the presence of transcription inhibitor, GnRH-induced augmentation of GnRH-R mRNA levels was completely abolished [32].
• Although it is known that GnRH induces luteinizing hormone beta (LHbeta) gene transcription, the mechanisms by which this occurs remain to be elucidated [20].

Other interactions of Gnrh1

• Coupling of the agonist-activated GnRH-R to both G(s) and G(i) proteins was demonstrated by the ability of nanomolar GnRH concentrations to reduce membrane-associated alpha(s) and alpha(i3) levels and of higher concentrations to diminish alpha(i3) levels [1].
• The percentage of GnRH neurons that double-labeled with NMDA-R1 was 2% in prepubertal rats and 3% in pubertal rats; this increased to 19% in postpubertal rats [2].
• In order to address this question, the present study examined the effects of direct intrahypothalamic perfusions with leptin on the in vivo release of GnRH in ovarian steroid-primed ovariectomized rats utilizing the push-pull perfusion technique [29].
• A slight but significant increase in GnRH pulse amplitude was caused by NPY (10(-7) M) in the female [31].
• However, GnRH pulse amplitude was not affected by a Y5-receptor antagonist (10(-6) M) while the interpulse interval was significantly increased as shown previously in the male [31].

Analytical, diagnostic and therapeutic context of Gnrh1

• Administration of the GnRH agonist readily prevented, for as long as 3 weeks, the stimulatory effects of castration on the GnRH-R mRNA and mRNAs for the beta-subunit of gonadotropins, but not for the alpha mRNA, which remained at a high level [33].
• We studied the expression patterns of GnRH and GnRH receptor (GnRH-R) in the same animals throughout the estrous cycle using real-time PCR [34].
• Production of IPs is an early response of GGH3 cells to a GnRH agonist, measurable at 15-30 min and maximal at 60 min after treatment with Buserelin in [3H]inositol preloaded cells [35].
• GnRH pulses were injected by a pump into a carotid cannula and animals received GnRH (25 ng/pulse) at various frequencies for 48 h [24].
• RNA samples were isolated from micropunches of the preoptic area and mediobasal hypothalamus from individual brain slices and GnRH mRNA levels in the preoptic area and GnRHR mRNA levels in the mediobasal hypothalamus were determined by competitive reverse transcription-polymerase chain reaction (RT-PCR) protocols [36].

References