Effects of Noradrenaline on GnRH-Secreting Immortalized Hypothalamic (GT1-7) Neurons.

Uemura, Tomohiro; Nishimura, Jun-ichi; Yamaguchi, Hideyo; Hiruma, Hiromi; Kimura, Fukuko; Minaguchi, Hiroshi

doi:10.1507/endocrj.44.73

Cited by 17 publications

(6 citation statements)

References 13 publications

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“…This regulation appears to involve α 1 -AR [52,53,54]. GT1-7 cells were previously shown to express some members of the α 1 - [55], α 2 - [56], and β 1 -subfamilies [57,58,59] of adrenoreceptors. Here we show that estradiol upregulates the expression of α 1 -AR, but not α 2 - or β-AR.…”

Section: Discussionmentioning

confidence: 99%

17-Beta-Estradiol Directly Regulates the Expression of Adrenergic Receptors and Kisspeptin/GPR54 System in GT1-7 GnRH Neurons

et al. 2007

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Estradiol plays a critical role in the feedback regulation of reproduction, in part by modulating the neurosecretory activity of gonadotropin-releasing hormone (GnRH) neurons. While indirect effects of estradiol on GnRH neurons have been clearly demonstrated, direct actions are still controversial. In the current study, we examined direct effects of 17β-estradiol upon the expression of receptors for afferent signals at the level of the GnRH neuron, using immortalized GT1-7 cells. Using RT-PCR, we confirmed the expression of mRNA for the adrenergic receptors (AR) α₁A-, α₁B-, α₁D-, α₂A-, α₂C-, and β₁-AR, and showed for the first time that mRNAs for α₂B-, β₂- and β₃-AR, for kisspeptin and its receptor GPR54 and for the novel estrogenic receptor GPR30 are expressed in GT1-7 cells. After treatment with 10 nM 17β-estradiol, α₁B-AR mRNA was significantly increased (14-fold) after 6 h as determined by real-time PCR, while α₁B- and α₁D-AR mRNA were significantly increased (19- and 23-fold, respectively) after 24 h. The expression of KiSS-1 and GPR54 mRNAs were also significantly increased (8- and 6-fold, respectively) after 24 h treatment of GT1-7 cells with estradiol. GPR30 mRNA expression was not affected by estradiol. Our data also showed that kisspeptin-10 (1–10 nM) can significantly stimulate GnRH release and GnRH mRNA expression in GT1-7 cells. These results suggest that the complex physiologic effects of estradiol on the function of the reproductive axis could be mediated partly through direct modulation of the expression of receptors for afferent signals in GnRH neurons.

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Section: Discussionmentioning

confidence: 99%

17-Beta-Estradiol Directly Regulates the Expression of Adrenergic Receptors and Kisspeptin/GPR54 System in GT1-7 GnRH Neurons

et al. 2007

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“…The modulation of GnRH pulse amplitude and frequency by GnRH agonist and antagonist analogs in cultured hypothalamic neurons and GT1-7 cells indicates the potential role of autocrine control of GnRH release. The in vivo operation of the GnRH oscillator is influenced by neuropeptides (30,31), neurotransmitters (32)(33)(34)(35)(36), peripheral hormones (37,38), and feedback actions of gonadal steroids (39 -42).…”

Section: Discussionmentioning

confidence: 99%

Muscarinic Regulation of Intracellular Signaling and Neurosecretion in Gonadotropin-Releasing Hormone Neurons

Krsmanović

1998

Endocrinology

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Agonist activation of cholinergic receptors expressed in perifused hypothalamic and immortalized GnRH-producing (GT1-7) cells induced prominent peaks in GnRH release, each followed by a rapid decrease, a transient plateau, and a decline to below basal levels. The complex profile of GnRH release suggested that acetylcholine (ACh) acts through different cholinergic receptor subtypes to exert stimulatory and inhibitory effects on GnRH release. Whereas activation of nicotinic receptors caused a transient increase in GnRH release, activation of muscarinic receptors inhibited basal GnRH release. Nanomolar concentrations of ACh caused dose-dependent inhibition of cAMP production that was prevented by pertussis toxin (PTX), consistent with the activation of a plasma-membrane G i protein. Micromolar concentrations of ACh also caused an increase in phosphoinositide hydrolysis that was inhibited by the M 1 receptor antagonist, pirenzepine. In ACh-treated cells, immunoblot analysis revealed that membrane-associated G ␣q/11 immunoreactivity was decreased after 5 min but was restored at later times. In contrast, immunoreactive G ␣i3 was decreased for up to 120 min after ACh treatment. The agonistinduced changes in G protein ␣-subunits liberated during activation of muscarinic receptors were correlated with regulation of their respective transduction pathways. These results indicate that ACh modulates GnRH release from hypothalamic neurons through both M 1 and M 2 muscarinic receptors. These receptor subtypes are coupled to G q and G i proteins that respectively influence the activities of PLC and adenylyl cyclase/ion channels, with consequent effects on neurosecretion. (Endocrinology 139: [4037][4038][4039][4040][4041][4042][4043] 1998) T HE DIVERSE actions of acetylcholine (ACh) are mediated by activation of nicotinic (ionotropic) and muscarinic (metabotropic) classes of receptors. Nicotinic receptors (nAChRs) are ligand gated receptor channels that are cation-specific but do not distinguish readily among cations (1). Of the five subtypes (M 1 -M 5 ) of muscarinic receptors (mAChRs), M 1 , M 3 , and M 5 are coupled to G q/11 and mediate activation of phospholipase C (PLC) and InsP 3 /Ca 2ϩ signaling. The M 2 and M 4 subtypes are coupled to G i/o , and mediate inhibition of cAMP production (2). Both classes of cholinergic receptors are expressed throughout the brain and are abundant in the hypothalamus, where monoaminergic neurons that terminate on GnRH and other peptidergic neurons are located (3).The GnRH neurons of the hypothalamus are innervated by noradrenergic neurons located in the hindbrain, and catecholamines have been implicated in the regulation of GnRH release. In contrast, there is less evidence for a role of cholinergic innervation in the control of GnRH secretion. In early studies, a rapid atropine-sensitive cholinergic component was found to be involved in the release of ovulating hormone in rats and rabbits (4, 5). Subsequently, intraventricular administration of atropine was shown to block the rel...

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“…The pubertal increase in GnRH secretion depends on the stimulatory actions of the neurotransmitter kisspeptin via the G protein-coupled receptor 54 (15,16) and presumably occurs by Ca 2+ entry through voltage-gated Ca 2+ channels or by Ca 2+ release from intracellular stores (10)(11)(12)(13)(14)17) after kisspeptin excitation of GnRH neurons. Kisspeptin (15,16), along with other neurotransmitters and hormones (18)(19)(20)(21)(22)(23), may convey information from presynaptic neurons about age, growth, availability of metabolic fuels such as glucose and fats (perhaps through insulin and leptin), circadian rhythm, and other factors.…”

mentioning

confidence: 99%

Calcium and Small-Conductance Calcium-Activated Potassium Channels in Gonadotropin-Releasing Hormone Neurons before, during, and after Puberty

Spergel

2007

Endocrinology

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The pubertal increase in GnRH secretion resulting in sexual maturation and reproductive competence is a complex process involving kisspeptin stimulation of GnRH neurons and requiring Ca(2+) and possibly other intracellular messengers. To determine whether the expression of Ca(2+) channels, or small-conductance Ca(2+)-activated K(+) (SK) channels, whose activity reflects cytoplasmic free Ca(2+) concentration, changes at puberty in GnRH neurons, Ca(2+) and SK currents in GnRH neurons were recorded in brain slices of juvenile [postnatal day (P) 10-21], pubertal (P28-P42), and adult (> or =P56) male GnRH-green fluorescent protein transgenic mice using perforated-patch and whole-cell techniques. Ca(2+) currents were inhibited by the Ca(2+) channel blocker Cd(2+) and showed marked heterogeneity but were on average similar in juvenile, pubertal, and adult GnRH neurons. SK currents, which were inhibited by the SK channel blocker apamin and enhanced by the SK and intermediate-conductance Ca(2+)-activated K(+) channel activator 1-ethyl-2-benzimidazolinone, were also on average similar in juvenile, pubertal, and adult GnRH neurons. These findings suggest that whereas Ca(2+) and SK channels may participate in the pubertal increase in GnRH secretion and there may be changes in Ca(2+) or SK channel subtypes, overall Ca(2+) and SK channel expression in GnRH neurons remains relatively constant across pubertal development. Hence, the expected increase in GnRH neuron cytoplasmic free Ca(2+) concentration required for increased GnRH secretion at puberty appears to be due to mechanisms other than altered Ca(2+) or SK channel expression, e.g. increased membrane depolarization and subsequent activation of preexisting Ca(2+) channels after increased excitatory synaptic input.

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Effects of Noradrenaline on GnRH-Secreting Immortalized Hypothalamic (GT1-7) Neurons.

Cited by 17 publications

References 13 publications

17-Beta-Estradiol Directly Regulates the Expression of Adrenergic Receptors and Kisspeptin/GPR54 System in GT1-7 GnRH Neurons

17-Beta-Estradiol Directly Regulates the Expression of Adrenergic Receptors and Kisspeptin/GPR54 System in GT1-7 GnRH Neurons

Muscarinic Regulation of Intracellular Signaling and Neurosecretion in Gonadotropin-Releasing Hormone Neurons

Calcium and Small-Conductance Calcium-Activated Potassium Channels in Gonadotropin-Releasing Hormone Neurons before, during, and after Puberty

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