Glutamatergic regulation of gonadotropin-releasing hormone neurons

Jennes, Lothar; Lin, Wei Yu; Lakhlani, Shruti

doi:10.1016/s0079-6123(02)41093-x

Cited by 19 publications

(7 citation statements)

References 38 publications

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“…Previous studies have shown that glutamate‐containing presynaptic terminals provide an abundant innervation of GnRH neurones which, together with extensive pharmacological and physiological evidence, supports the view that glutamate is an important transmitter for the control of GnRH neuronal activity (4, 43).…”

Section: Discussionmentioning

confidence: 67%

Expression and Activation of N‐Methyl‐d‐Aspartate Receptor Subunit‐1 Receptor Subunits in Gonadotrophin‐Releasing Hormone Neurones of Young and Middle‐Aged Mice During the Luteinising Hormone Surge

Adjan

Centers

Jennes

2008

J Neuroendocrinology

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Glutamate is an important excitatory neurotransmitter that stimulates the release of gonadotrophin-releasing hormone (GnRH) and participates in the generation of the luteinising hormone (LH) surge. To determine the mechanisms of action of glutamate and possible changes in the glutamatergic input to GnRH neurones during reproductive ageing, we measured the expression and activation of the mandatory N-methyl-D-aspartate receptor subunit-1 (NMDAR1) in GnRH neurones of young and middle-aged mice prior to and during a steroid-induced LH surge. The results show that, in young animals, approximately 55% of all GnRH neurones contain immunoreactive NMDAR1 protein and this percentage does not change during the day of the LH surge. In approximately 10% of the GnRH neurones, NMDA receptor protein is phosphorylated at Ser 890 prior to the surge, whereas, in approximately 55% of the GnRH neurones, NMDAR1 subunits are phosphorylated during the LH surge. Activation of NMDAR1 receptor subunits stimulates the calcium-calmodulin-kinase IV (CaMK IV). pathway, which leads to the translocation of CaMK IV into the nucleus where this enzyme can phosphorylate the cAMP response element-binding protein (CREB) and CREB-binding protein. We show that, in young animals, approximately 20% of the GnRH neurones contain CaMK IV in their nuclei 7 h prior to the LH surge; this percentage increases to 60% at the beginning of the surge and decreases to approximately 40% some 2 h into the LH surge. In middle-aged animals, approximately 25% of the GnRH neurones contain NMDAR1 protein and only 10% of the GnRH neurones contain phosphorylated NMDAR1 protein prior to and during the surge; however 2 h after the peak of the surge, 20% of the GnRH neurones contain phosphorylated NMDAR1 subunits. Similarly, 20% of GnRH neurones contain nuclear CaMK IV and this percentage does not change during the day of the LH surge. The results suggest that, in the young animal, glutamatergic innervation of GnRH neurones during the LH surge causes the activation and phosphorylation of NMDAR1 receptor subunits which results in the translocation of CaMK IV into the nucleus. However, both, the expression and activation of NMDAR1 receptor subunits are greatly reduced in the middle-aged animals, which could result in the absence of LH surges.

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Section: Discussionmentioning

confidence: 67%

Expression and Activation of N‐Methyl‐d‐Aspartate Receptor Subunit‐1 Receptor Subunits in Gonadotrophin‐Releasing Hormone Neurones of Young and Middle‐Aged Mice During the Luteinising Hormone Surge

Adjan

Centers

Jennes

2008

J Neuroendocrinology

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“…There is accumulating evidence that OFQ is able to inhibit the K + -evoked release of glutamate and suppress glutamate transmission in the central nervous system of various species [23][24][25] . There is a general agreement that the glutamatergic pathway is a major excitory element in the regulation of GnRH release [26] . We speculate that hypothalamic glutamate might mediate the inhibitory effects of OFQ on GnRH secretion.…”

Section: Discussionmentioning

confidence: 99%

Involvement of nociceptin/orphanin FQ in release of hypothalamic GnRH mediated by ORL1 receptor in ovariectomized rats

Chen

et al. 2005

Acta Pharmacologica Sinica

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Aim: To investigate effect of the nociceptin/orphanin FQ (OFQ) on hypothalamus gonadotropin‐releasing hormone (GnRH) release in ovariectomized (OVX) rats. Methods: GnRH radioimmunoassay (RIA) was used to study the effect of OFQ on GnRH release in hypothalamus slices in vitro. Push‐pull perfusion and intracerebroventicular (icv) injection were used to examine the effect of OFQ on GnRH release in the hypothalamus medial preoptic area (POA) in vivo. Ovariectomies were performed on female Sprague‐Dawley rats, and their plasma luteinizing hormone (LH) levels were measured after icv injection of OFQ with or without [Nphe1]NC(l‐13)NH2,a competitive antagonist of opioid receptor‐like 1 receptor (ORL1 receptor). Reverse transcription‐polymerase chain reaction (RT‐PCR) was used to investigate the expression of the ORL1 receptor in rat pituitary. Results: GnRH release from hypothalamus slices was inhibited 90 min after the administration of 2 mmol/L and 20 mmol/L OFQ (P<0.05). Accordingly, GnRH release from hypothalamus POA was also significantly reduced by the injection of 0.2 mmol/L and 2 mmol/L OFQ. Plasma LH levels were also decreased significantly 2h after icv injection of 20 nmol OFQ in OVX rats (P<0.05) and this effect could be abolished by pretreatment with 20 nmol [Nphe1]NC(1‐13)NH2, that is, NC13. More interestingly, plasma LH levels in OVX rats increased markedly 2 h after icv injection of 100 nmol and 200 nmol NC13. RT‐PCR analysis further revealed that the ORL1 receptor was not expressed in the pituitary of OVX rats. Conclusion: Central administration of nociceptin/orphanin FQ might inhibit the release of hypothalamic GnRH and decrease the plasma LH levels through ORL1 receptors in OVX rats.

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“…Of these, glutamate is the most abundant in the brain (Brann, 1995; Brann and Mahesh, 1994). Immunohistochemical and in situ hybridization studies examining glutamate receptor localization in the hypothalamus have shown their presence in a variety of hypothalamic nuclei, including medial preoptic nucleus (MPN), median preoptic nucleus, arcuate nucleus (ARC), dorsomedial, and ventromedial hypothalamic nuclei, supraoptic nucleus, suprachiasmatic nucleus, and paraventricular nucleus (Brann, 1995; Jennes et al , 2002). Additionally, immunohistochemical analysis of glutamatergic fibers in the hypothalamus has shown them to be in close proximity with GnRH perikarya in the preoptic area, and GnRH axons in the median eminence (Eyigor and Jennes, 1996; Kawakami et al , 1998b).…”

Section: Glutamate and The Hpg Axismentioning

confidence: 99%

Chapter 2 Hypothalamic Neural Systems Controlling the Female Reproductive Life Cycle

Maffucci

Gore

2009

International Review of Cell and Molecular Biology

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The hypothalamic-pituitary-gonadal (HPG) axis undergoes a number of changes throughout the reproductive life cycle that are responsible for the development, puberty, adulthood, and senescence of reproductive systems. This natural progression is dictated by the neural network controlling the hypothalamus including the cells that synthesize and release gonadotropin-releasing hormone (GnRH) and their regulatory neurotransmitters. Glutamate and GABA are the primary excitatory and inhibitory neurotransmitters in the central nervous system, and as such contribute a great deal to modulating this axis throughout the lifetime via their actions on receptors in the hypothalamus, both directly on GnRH neurons as well as indirectly though other hypothalamic neural networks. Interactions among GnRH neurons, glutamate, and GABA, including the regulation of GnRH gene and protein expression, hormone release, and modulation by estrogen, are critical to age-appropriate changes in reproductive function. Here, we present evidence for the modulation of GnRH neurosecretory cells by the balance of glutamate and GABA in the hypothalamus, and the functional consequences of these interactions on reproductive physiology across the life cycle.

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Glutamatergic regulation of gonadotropin-releasing hormone neurons

Cited by 19 publications

References 38 publications

Expression and Activation of N‐Methyl‐d‐Aspartate Receptor Subunit‐1 Receptor Subunits in Gonadotrophin‐Releasing Hormone Neurones of Young and Middle‐Aged Mice During the Luteinising Hormone Surge

Expression and Activation of N‐Methyl‐d‐Aspartate Receptor Subunit‐1 Receptor Subunits in Gonadotrophin‐Releasing Hormone Neurones of Young and Middle‐Aged Mice During the Luteinising Hormone Surge

Involvement of nociceptin/orphanin FQ in release of hypothalamic GnRH mediated by ORL1 receptor in ovariectomized rats

Chapter 2 Hypothalamic Neural Systems Controlling the Female Reproductive Life Cycle

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