scholarly journals Developmental Increase in Kisspeptin-54 Release in Vivo Is Independent of the Pubertal Increase in Estradiol in Female Rhesus Monkeys (Macaca mulatta)

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1887-1897 ◽  
Author(s):  
Kathryn A. Guerriero ◽  
Kim L. Keen ◽  
Ei Terasawa
Keyword(s):  
Rhesus Monkeys ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Release Pattern ◽  
Female Rhesus ◽  
Gnrh Release ◽  
Important Regulator ◽  
Nocturnal Increase

Kisspeptin (KP) signaling has been proposed as an important regulator in the mechanism of puberty. In this study, to determine the role of KP in puberty, we assessed the in vivo release pattern of KP-54 from the basal hypothalamus/stalk-median eminence in prepubertal and pubertal ovarian-intact female rhesus monkeys. We found that there was a developmental increase in mean KP-54 release, pulse frequency, and pulse amplitude, which is parallel to the developmental changes in GnRH release that we previously reported. Moreover, a nocturnal increase in KP-54 release becomes prominent after the onset of puberty. Because the pubertal increase in GnRH release occurs independent of the pubertal increase in circulating gonadal steroids, we further examined whether ovariectomy (OVX) modifies the release pattern of KP-54. Results show that OVX in pubertal monkeys enhanced mean KP-54 release and pulse amplitude but not pulse frequency, whereas OVX did not alter the release pattern of KP-54 in prepubertal monkeys. Estradiol replacement in OVX pubertal monkeys suppressed mean KP-54 release and pulse amplitude but not pulse frequency. Estradiol replacement in OVX prepubertal monkeys did not alter the KP-54 release pattern. Collectively these results suggest that the pubertal increase in KP release occurs independent of the pubertal increase in circulating estradiol. Nevertheless, the pubertal increase in KP release is not likely responsible for the initiation of the pubertal increase in GnRH release. Rather, after puberty onset, the increase in KP release contributes to further increase GnRH release during the progression of puberty.

scholarly journals An increase in in vivo release of LHRH and precocious puberty by posterior hypothalamic lesions in female rhesus monkeys (Macaca mulatta)

2007 ◽  
Vol 292 (4) ◽  
pp. E1000-E1009 ◽  
Author(s):  
Bret M. Windsor-Engnell ◽  
Etsuko Kasuya ◽  
Masaharu Mizuno ◽  
Kim L. Keen ◽  
Ei Terasawa
Keyword(s):  
Precocious Puberty ◽  
Rhesus Monkeys ◽  
Gaba Release ◽  
Good Tool ◽  
Subsequent Increase ◽  
Female Rhesus ◽  
Before And After ◽  
Lhrh Release

We have previously shown that a decrease in γ-aminobutyric acid (GABA) tone and a subsequent increase in glutamatergic tone occur in association with the pubertal increase in luteinizing hormone releasing hormone (LHRH) release in primates. To further determine the causal relationship between developmental changes in GABA and glutamate levels and the pubertal increase in LHRH release, we examined monkeys with precocious puberty induced by lesions in the posterior hypothalamus (PH). Six prepubertal female rhesus monkeys (17.4 ± 0.1 mo of age) received lesions in the PH, three prepubertal females (17.5 ± 0.1 mo) received sham lesions, and two females received no treatments. LHRH, GABA, and glutamate levels in the stalk-median eminence before and after lesions were assessed over two 6-h periods (0600–1200 and 1800–2400) using push-pull perfusion. Monkeys with PH lesions exhibited external signs of precocious puberty, including significantly earlier menarche in PH lesion animals (18.8 ± 0.2 mo) than in sham/controls (25.5 ± 0.9 mo, P < 0.001). Moreover, PH lesion animals had elevated LHRH levels and higher evening glutamate levels after lesions, whereas LHRH changes did not occur in sham/controls until later. Changes in GABA release were not discernible, since evening GABA levels already deceased at 18–20 mo of age in both groups and morning levels remained at the prepubertal levels. The age of first ovulation in both groups did not differ. Collectively, PH lesions may not be a good tool to investigate the mechanism of puberty, and, taking into account the recent findings on the role of kisspeptins, the mechanism of the puberty onset in primates is more complex than we initially anticipated.

scholarly journals Developmental Changes in GnRH Release in Response to Kisspeptin Agonist and Antagonist in Female Rhesus Monkeys (Macaca mulatta): Implication for the Mechanism of Puberty

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 825-836 ◽  
Author(s):  
Kathryn A. Guerriero ◽  
Kim L. Keen ◽  
Robert P. Millar ◽  
Ei Terasawa
Keyword(s):  
Rhesus Monkeys ◽  
Developmental Stages ◽  
Developmental Changes ◽  
Partial Recovery ◽  
Ovarian Steroid ◽  
Medial Basal Hypothalamus ◽  
Female Rhesus ◽  
Gnrh Release ◽  
Agonist And Antagonist

Kisspeptin (KP) and KP-1 receptor (KISS1R) have emerged as important upstream regulators in the control of puberty. However, how developmental changes in KP-KISS1R contribute to the pubertal increase in GnRH release still remains elusive. In this study, we examined the effects of the KP agonist, human KP-10 (hKP-10), and the KP antagonist, peptide 234, on in vivo GnRH release in prepubertal and pubertal ovarian-intact female rhesus monkeys using a microdialysis method. We found that direct infusion of hKP-10 into the medial basal hypothalamus and stalk-median eminence region stimulated GnRH release in a dose-responsive manner, whereas infusion of peptide 234 suppressed GnRH release in both developmental stages. Because ovarian steroid feedback on GnRH release becomes prominent after the initiation of puberty in primates, we further examined whether ovarian steroids modify the GnRH response to hKP-10. Results demonstrate that the hKP-10-induced stimulation of GnRH release was eliminated by ovariectomy in pubertal, but not prepubertal, monkeys. Furthermore, replacement of estradiol into ovariectomized pubertal monkeys resulted in a partial recovery of the hKP-10-induced GnRH release. Collectively, these results suggest that a KISS1R-mediated mechanism, in addition to the pubertal increase in KP-54 release we previously reported, contributes to the pubertal increase in GnRH release and that there is a switch from an ovarian steroid-independent to -dependent mechanism in the response of GnRH to KP.

scholarly journals An Increase in Kisspeptin-54 Release Occurs with the Pubertal Increase in Luteinizing Hormone-Releasing Hormone-1 Release in the Stalk-Median Eminence of Female Rhesus Monkeys in Vivo

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4151-4157 ◽  
Author(s):  
Kim L. Keen ◽  
Frederick H. Wegner ◽  
Stephen R. Bloom ◽  
Mohammad A. Ghatei ◽  
Ei Terasawa
Keyword(s):  
Median Eminence ◽  
Rhesus Monkeys ◽  
Dependent Manner ◽  
Microdialysis Probe ◽  
Female Rhesus ◽  
Nocturnal Increase ◽  
Pooled Samples ◽  
G Protein Coupled ◽  
Dose Dependent

The G-protein coupled receptor GPR54 and its ligand, KiSS-1-derived peptide kisspeptin-54, appear to play an important role in the mechanism of puberty. This study measures the release of kisspeptin-54 in the stalk-median eminence (S-ME) during puberty and examines its potential role in the pubertal increase in LHRH-1 release in female rhesus monkeys. First, developmental changes in release of kisspeptin-54 and LHRH-1 were assessed in push-pull perfusate samples obtained from the S-ME of prepubertal, early pubertal, and midpubertal female rhesus monkeys. Whereas LHRH-1 levels in 10-min intervals had been measured previously for other experiments, kisspeptin-54 levels in 40-min pooled samples were newly measured by RIA. The results indicate that a significant increase in kisspeptin-54 release occurred in association with the pubertal increase in LHRH-1 release and that a nocturnal increase in kisspeptin-54 release was already observed in prepubertal monkeys and continued through the pubertal period. Second, we measured kisspeptin-54 release in the S-ME of midpubertal monkeys at 10-min intervals using a microdialysis method. Kisspeptin-54 release in the S-ME was clearly pulsatile with an interpulse interval of about 60 min, and approximately 75% of kisspeptin-54 pulses were correlated with LHRH-1 pulses. Finally, the effect of kisspeptin-10 on LHRH-1 release was examined with the microdialysis method. Kisspeptin-10 infusion through a microdialysis probe significantly stimulated LHRH-1 release in a dose-dependent manner. Collectively, the results are consistent with the hypothesis that kisspeptin plays a role in puberty.

scholarly journals Activin A regulates activation of mouse neutrophils by Smad3 signalling

Open Biology ◽  
2017 ◽  
Vol 7 (5) ◽  
pp. 160342 ◽  
Author(s):  
Yan Qi ◽  
Jingyan Ge ◽  
Chunhui Ma ◽  
Na Wu ◽  
Xueling Cui ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Activin A ◽  
Target Cells ◽  
Inflammatory Factor ◽  
Important Regulator ◽  
Growth Factor Beta ◽  
Species Production

Activin A, a member of the transforming growth factor beta superfamily, acts as a pro-inflammatory factor in acute phase response, and influences the pathological progress of neutrophil-mediated disease. However, whether activin A can exert an effect on the activities of neutrophils remains unclear. In this study, we found that the release of activin A was enhanced from neutrophils of mouse when stimulated with lipopolysaccharide. Furthermore, neutrophils were not only the source of activin A but also the target cells in response to activin A, in which canonical activin signalling components existed, and levels of ACTRIIA, SMAD3 and p-SMAD3 proteins were elevated in activin A-treated neutrophils. Next, the role of activin A was determined in regulation of neutrophils activities. Our data revealed that activin A induced O 2 − release and reactive oxygen species production, promoted IL-6 release, and enhanced phagocytosis, but failed to attract neutrophils migrating across the trans-well membrane. Moreover, we found that effect of activin A on IL-6 release from the peritoneal neutrophils of mouse was significantly attenuated by in vivo Smad3 knockdown. In summary, these data demonstrate that activin A can exert an effect on neutrophils activation in an autocrine/paracrine manner through Smad3 signalling, suggesting that activin A is an important regulator of neutrophils.

scholarly journals Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4993-5001 ◽  
Author(s):  
Chad D. Foradori ◽  
Marcel Amstalden ◽  
Lique M. Coolen ◽  
Sushma R. Singh ◽  
Christine J. McManus ◽  
...  
Keyword(s):  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Brain Regions ◽  
Orphanin Fq ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
External Zone ◽  
Gnrh Secretion

Orphanin FQ (OFQ), also known as nociceptin, is a member of the endogenous opioid peptide family that has been functionally implicated in the control of pain, anxiety, circadian rhythms, and neuroendocrine function. In the reproductive system, endogenous opioid peptides are involved in the steroid feedback control of GnRH pulses and the induction of the GnRH surge. The distribution of OFQ in the preoptic area and hypothalamus overlaps with GnRH, and in vitro evidence suggests that OFQ can inhibit GnRH secretion from hypothalamic fragments. Using the sheep as a model, we examined the potential anatomical colocalization between OFQ and GnRH using dual-label immunocytochemistry. Confocal microscopy revealed that approximately 93% of GnRH neurons, evenly distributed across brain regions, were also immunoreactive for OFQ. In addition, almost all GnRH fibers and terminals in the external zone of the median eminence, the site of neurosecretory release of GnRH, also colocalized OFQ. This high degree of colocalization suggested that OFQ might be functionally important in controlling reproductive endocrine events. We tested this possibility by examining the effects of intracerebroventricular administration of [Arg14, Lys15] OFQ, an agonist to the OFQ receptor, on pulsatile LH secretion. The agonist inhibited LH pulse frequency in both luteal phase and ovariectomized ewes and suppressed pulse amplitude in the latter. The results provide in vivo evidence supporting a role for OFQ in the control of GnRH secretion and raise the possibility that it acts as part of an ultrashort, autocrine feedback loop controlling GnRH pulses.

scholarly journals Effect of Continuous Intravenous Administration of Human Metastin 45–54 on the Neuroendocrine Activity of the Hypothalamic-Pituitary-Testicular Axis in the Adult Male Rhesus Monkey (Macaca mulatta)

Endocrinology ◽  
2007 ◽  
Vol 148 (7) ◽  
pp. 3364-3370 ◽  
Author(s):  
Suresh Ramaswamy ◽  
Stephanie B. Seminara ◽  
Clifford R. Pohl ◽  
Meloni J. DiPietro ◽  
William F. Crowley ◽  
...  
Keyword(s):  
Adult Male ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
High Dose ◽  
Continuous Exposure ◽  
Continuous Administration ◽  
Marked Rise ◽  
Lh Release ◽  
G Protein Coupled

In agonadal juvenile male monkeys, continuous administration of human metastin 45–54 (hu metastin 45–54) leads to desensitization of its receptor, G protein-coupled receptor 54 (GPR54), and decreased LH. The present study extended this observation to the adult male monkey, a more preclinically relevant model in which robust activity in the hypothalamic-pituitary-testicular axis is present. Continuous iv infusion of hu metastin 45–54 at either 200 or 400 μg/h elicited a marked rise in circulating LH that peaked 2–3 h after initiation of treatment. Thereafter, levels declined, and by 24 h, LH in metastin 45–54-infused animals was similar to control. LH release in response to an iv bolus of hu metastin 45–54 (10–30 μg) during the final 3 h of continuous infusion was truncated or abolished (low and high peptide dose, respectively). GPR54 desensitization by the high-dose metastin 45–54 infusion was associated with compromised pituitary response to a bolus GnRH injection (0.3 μg). LH pulse amplitude and pulse frequency were markedly suppressed during high-dose metastin 45–54 treatment. Surprisingly, the fidelity of the relationship between circulating testosterone (T) and LH was distorted during the high-dose peptide infusion. Thus, for a given concentration of LH, T levels were invariably higher during the high-dose metastin 45–54 infusion than during vehicle, suggesting that the peptide may exert direct actions on the testis to amplify T production. These findings support the notion that GPR54 is desensitized by continuous exposure to ligand, and they raise the possibility of an intratesticular role of GPR54.

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