Naloxone Increases the Frequency of the Electrical Activity of Luteinizing Hormone-Releasing Hormone Pulse Generator in Long-Term Ovariectomized Rats

Kimura, Fukuko; Nishihara, Masugi; Hiruma, Hiromi; Funabashi, Toshiya

doi:10.1159/000125704

Cited by 91 publications

(80 citation statements)

References 24 publications

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“…Data analysis: Since secretory profiles of GH, GHRH and SRIF were found to be episodic, and pulse detection was done based on the methods reported previously [11,13,23]. A pulse was defined when CVs of assay values composing both ascending and descending phases of each peak exceeded 2 times the corresponding intraassay CV calculated for the pulse detection in each assay.…”

Section: Icv Injection Of Npy Galanin and Ghrelinmentioning

confidence: 99%

Relationship between Growth Hormone (GH) Pulses in the Peripheral Circulation and GH-Releasing Hormone and Somatostatin Profiles in the Cerebrospinal Fluid of Goats

Mogi

Yonezawa

Chen

et al. 2004

The Journal of Veterinary Medical Science

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ABSTRACT. Growth hormone (GH) is secreted in a pulsatile manner, but the underlying mechanisms of GH pulse generation remain to be resolved. In the present study, we investigated the relationship between GH pulses in the peripheral circulation and GH-releasing hormone (GHRH) and somatostatin (SRIF) profiles in the cerebrospinal fluid (CSF) of male goats. The effects of an intracerebrovent ricular (icv) injection of neuropeptide Y (NPY), galanin and ghrelin were also analyzed. Blood and CSF samples were collected every 15 min for 8 hr from the jugular vein and third ventricle, respectively. GH pulsatility in the goat was found to consist of distinct large pulses of 5 hr periodicity and small pulses of 1 hr periodicity. GHRH and SRIF in the CSF fluctuated in a pulsatile manner with 1 hr periodicity, and most of the descending phase of SRIF pulses were associated with the initiation of GH pulses. Icv injections of NPY, galanin and ghrelin stimulated GHRH release without affecting SRIF release. In addition, NPY suppressed, and galanin and ghrelin induced large GH pulses, although ghrelin was much more effective than galanin. These results suggest that an hourly fall in SRIF is involved in generating intrinsic circhoral rhythm of GH pulsatility. The mechanisms underlying the generation of large GH pulses of 5 hr periodicity remain unknown, while direct action of NPY and/or ghrelin on the pituitary might be involved. KEY WORDS: ghrelin, growth hormone, growth hormone-releasing hormone, NPY, somatostatin.J. Vet. Med. Sci. 66(9): 1071-1078, 2004 Growth hormone (GH) is secreted in a pulsatile manner in all mammalian species studied to date, and this pulsatility plays an important role in the regulation of somatic growth and metabolism [7,10,15,20]. Knowledge of the exact mechanisms underlying the generation of GH pulses is, therefore, of physiological and pathophysiological importance. It is generally accepted that GH pulses are governed by two hypothalamic peptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), which are stimulatory and inhibitory for GH secretion, respectively [15,29,34,41]. Most studies on the neuroendocrine regulation of GH pulsatility have been performed in male rats, in which GH secretion is characterized by a strikingly regular ultradian rhythm with large secretory bursts of every 3-4 hr [15,41]. In the rat, indirect studies such as passive immunizations against GHRH and SRIF suggested that GH pulses depend on GHRH discharge in combination with a decrease in SRIF secretion [29,41]. However, the secretory profiles of GHRH and SRIF under physiological conditions in this species remain to be elucidated because of the technical difficulties involved in collecting pituitary portal blood from unanesthetized animals. On the other hand, direct measurement of GHRH and SRIF in the portal blood from conscious animals has been reported in the sheep [4,12,44]. According to these studies, GH pulsatility in the sheep seemed less regular and the secretory patterns of GHRH and SRIF seemed more complex than ...

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Section: Icv Injection Of Npy Galanin and Ghrelinmentioning

confidence: 99%

Relationship between Growth Hormone (GH) Pulses in the Peripheral Circulation and GH-Releasing Hormone and Somatostatin Profiles in the Cerebrospinal Fluid of Goats

Mogi

Yonezawa

Chen

et al. 2004

The Journal of Veterinary Medical Science

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“…Blood samples (0.3 ml) were taken every 6 min for 2 h through the intra-atrial cannula and an equal volume of heparinized saline containing naloxone (Sigma Chemical Co., St Louis, MO, USA) (0.5 mg/kg per h) or heparinized saline only was replaced after each bleeding (16,17). Rats were divided into three experimental groups: group 1, 3V saline þ i.v.…”

Section: Administration Of 2-b4omentioning

confidence: 99%

“…Funabashi et al (16) reported that, in ovx rats, intermittent administration of naloxone in the same dose as we used resulted in a significant increase in the mean LH concentration. Kimura et al (17) reported that the same intermittent administration of naloxone in ovx rats significantly increased the frequency and the duration of multiunit activity volleys that accompanied the initiation of each LH pulse. In the present study, naloxone did not increase the mean LH concentrations; therefore, the suppressive effect of 2-B4O on the pituitary response to GnRH might not be completely blocked by administration of naloxone.…”

Section: Figurementioning

confidence: 99%

The endogenous feeding suppressant, 2-buten-4-olide, impairs the pulsatile secretion of luteinizing hormone through endogenous opioid peptides

Kaji

Saito

Shitsukawa

et al. 1998

European Journal of Endocrinology

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Objective: To clarify the mechanism of the suppressive effect of 2-buten-4-olide (2-B4O), an endogenous feeding suppressant, on the pulsatile secretion of luteinizing hormone (LH), by studying whether endogenous opioid peptides are involved in this suppressive effect. Methods: Using ovariectomized (ovx) rats, blood samples were taken every 6 min for 2 h after administration of 2-B4O or saline into the third cerebroventricle (3V) and sequential i.v. injection of naloxone (0.5 mg/kg per h) or saline. Rats were divided into three experimental groups: group 1: 3V saline þ i.v. saline (control); group 2: 3V 2-B4O þ i.v. saline; group 3: 3V 2-B4O+i.v. naloxone. Serum LH concentrations were determined by double-antibody RIA. To determine whether 2-B4O affected the biosynthetic activity of the opioidergic neurons within the ovx rat arcuate nucleus, we measured the concentrations of pro-opiomelanocortin (POMC) mRNA, a precursor of b-endorphin, in the rostral arcuate nucleus using non-radioactive in situ hybridization and a computerized image-analysis system. Results: 2-B4O significantly suppressed the pulse frequency of LH (group 2: 1.5 Ϯ 0.33 pulses/2 h, group 1: 2.43 Ϯ 0.2 pulses/2 h; P < 0.05), but naloxone blocked its suppressive effect and restored the pulse frequency (group 3: 3.29 Ϯ 0.36 pulses/2 h, group 2: 1.5 Ϯ 0.33 pulses/2 h; P < 0.01). There were no significant changes in the mean LH concentrations and amplitude. Furthermore, 2-B4O significantly stimulated the expression of POMC mRNA in the rostral arcuate nucleus. Conclusion: These results suggest that 2-B4O may impair the pulsatile secretion of LH by activating the opioid pathway within the hypothalamus.

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“…Within this region, particular attention has been focused on the arcuate nucleus (ARN) (13,14), where studies have also recorded multiunit activity that correlates with pulsatile LH secretion in a variety of mammals (15)(16)(17)(18). Although the identity of the neural elements giving rise to multiunit activity are unknown, it has been suggested that they may represent the activity of kisspeptin neurons within the ARN (19).…”

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confidence: 99%

Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion

Han

McLennan

Czieselsky

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

160

111

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Normal reproductive functioning in mammals depends upon gonadotropin-releasing hormone (GnRH) neurons generating a pulsatile pattern of gonadotropin secretion. The neural mechanism underlying the episodic release of GnRH is not known, although recent studies have suggested that the kisspeptin neurons located in the arcuate nucleus (ARN) may be involved. In the present experiments we expressed channelrhodopsin (ChR2) in the ARN kisspeptin population to test directly whether synchronous activation of these neurons would generate pulsatile luteinizing hormone (LH) secretion in vivo. Characterization studies showed that this strategy targeted ChR2 to 70% of all ARN kisspeptin neurons and that, in vitro, these neurons were activated by 473-nm blue light with high fidelity up to 30 Hz. In vivo, the optogenetic activation of ARN kisspeptin neurons at 10 and 20 Hz evoked high amplitude, pulse-like increments in LH secretion in anesthetized male mice. Stimulation at 10 Hz for 2 min was sufficient to generate repetitive LH pulses. In diestrous female mice, only 20-Hz activation generated significant increments in LH secretion. In ovariectomized mice, 5-, 10-, and 20-Hz activation of ARN kisspeptin neurons were all found to evoke LH pulses. Part of the sex difference, but not the gonadal steroid dependence, resulted from differential pituitary sensitivity to GnRH. Experiments in kisspeptin receptor-null mice, showed that kisspeptin was the critical neuropeptide underlying the ability of ARN kisspeptin neurons to generate LH pulses. Together these data demonstrate that synchronized activation of the ARN kisspeptin neuronal population generates pulses of LH.GnRH | kisspeptin | optogenetics | arcuate nucleus | gonadal steroids

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Naloxone Increases the Frequency of the Electrical Activity of Luteinizing Hormone-Releasing Hormone Pulse Generator in Long-Term Ovariectomized Rats

Cited by 91 publications

References 24 publications

Relationship between Growth Hormone (GH) Pulses in the Peripheral Circulation and GH-Releasing Hormone and Somatostatin Profiles in the Cerebrospinal Fluid of Goats

Relationship between Growth Hormone (GH) Pulses in the Peripheral Circulation and GH-Releasing Hormone and Somatostatin Profiles in the Cerebrospinal Fluid of Goats

The endogenous feeding suppressant, 2-buten-4-olide, impairs the pulsatile secretion of luteinizing hormone through endogenous opioid peptides

Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion

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