scholarly journals Effects of KiSS-1 Peptide, the Natural Ligand of GPR54, on Follicle-Stimulating Hormone Secretion in the Rat

Endocrinology ◽  
2005 ◽  
Vol 146 (4) ◽  
pp. 1689-1697 ◽  
Author(s):  
V. M. Navarro ◽  
J. M. Castellano ◽  
R. Fernández-Fernández ◽  
S. Tovar ◽  
J. Roa ◽  
...  
Keyword(s):  
Excitatory Amino Acid ◽  
Hormone Secretion ◽  
Metastasis Suppressor ◽  
Experimental Conditions ◽  
Adult Rats ◽  
Gonadotropin Secretion ◽  
Neuroendocrine Control

Abstract KiSS-1 was originally identified as a metastasis suppressor gene encoding an array of structurally related peptides, namely kisspeptins, which acting through the G protein-coupled receptor GPR54 are able to inhibit tumor progression. Unexpectedly, a reproductive facet of this newly discovered system has recently arisen, and characterization of the role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion has been initiated. However, such studies have been so far mostly restricted to LH, and very little is known about the actual contribution of this system in the regulation of FSH release. To address this issue, the effects of KiSS-1 peptide on FSH secretion were monitored in vivo and in vitro under different experimental conditions. Intracerebroventricular administration of KiSS-1 peptide significantly stimulated FSH secretion in prepubertal and adult rats. Yet, dose-response analyses in vivo demonstrated an ED50 value for the FSH-releasing effects of KiSS-1 of 400 pmol, i.e. approximately 100-fold higher than that of LH. In addition, systemic (ip and iv) injection of KiSS-1 significantly stimulated FSH secretion in vivo. However, KiSS-1 failed to elicit basal FSH release directly at the pituitary level, although it moderately enhanced GnRH-stimulated FSH secretion in vitro. Finally, mechanistic studies revealed that the ability of KiSS-1 to elicit FSH secretion was abolished by the blockade of endogenous GnRH actions, but it was persistently observed in different models of leptin insufficiency and after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e. relevant signals in the neuroendocrine control of gonadotropin secretion. In summary, our results extend previous recent observations on the role of KiSS-1 in the control of LH secretion and provide solid evidence for a stimulatory effect of KiSS-1 on FSH release, acting at central level. Overall, it is proposed that the KiSS-1/GPR54 system is a novel, pivotal downstream element in the neuroendocrine network governing gonadotropin secretion.

scholarly journals Characterization of the Potent Luteinizing Hormone-Releasing Activity of KiSS-1 Peptide, the Natural Ligand of GPR54

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 156-163 ◽  
Author(s):  
V. M. Navarro ◽  
J. M. Castellano ◽  
R. Fernández-Fernández ◽  
S. Tovar ◽  
J. Roa ◽  
...  
Keyword(s):  
Excitatory Amino Acid ◽  
Hypogonadotropic Hypogonadism ◽  
Mrna Levels ◽  
Central Administration ◽  
Experimental Conditions ◽  
Gonadotropin Secretion ◽  
Neuroendocrine Control ◽  
Lh Secretion

Loss-of-function mutations of the gene encoding GPR54, the putative receptor for the KiSS-1-derived peptide metastin, have been recently associated with hypogonadotropic hypogonadism, in both rodents and humans. Yet the actual role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion remains largely unexplored. To initiate such analysis, the effects of KiSS-1 peptide on LH secretion were monitored using in vivo and in vitro settings under different experimental conditions. Central intracerebroventricular administration of KiSS-1 peptide potently elicited LH secretion in vivo over a range of doses from 10 pmol to 1 nmol. The effect of centrally injected KiSS-1 appeared to be mediated via the hypothalamic LHRH. However, no effect of central administration of KiSS-1 was detected on relative LHRH mRNA levels. Likewise, systemic (ip and iv) injection of KiSS-1 markedly stimulated LH secretion. This effect was similar in terms of maximum response to that of central administration of KiSS-1 and might be partially attributed to its ability to stimulate LH secretion directly at the pituitary. Finally, the LH-releasing activity of KiSS-1 was persistently observed after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e. relevant neurotransmitters in the neuroendocrine control of LH secretion. In summary, our results provide solid evidence for a potent stimulatory effect of KiSS-1 on LH release, acting at central levels (likely the hypothalamus) and eventually at the pituitary, and further document a novel role of the KiSS-1/GPR54 system as a relevant downstream element in the neuroendocrine network governing LH secretion.

Factors affecting in vitro and in vivo antioxidant effects. Experimental conditions and nature of oxidants determine antioxidant efficacy

2021 ◽  
pp. 1-9
Author(s):  
Etsuo Niki
Keyword(s):  
Biological Molecules ◽  
Experimental Conditions ◽  
Factors Affecting ◽  
Beneficial Effects ◽  
Multiple Oxidants ◽  
Antioxidant Effects

Reactive oxygen and nitrogen species have been implicated in the onset and progression of various diseases and the role of antioxidants in the maintenance of health and prevention of diseases has received much attention. The action and effect of antioxidants have been studied extensively under different reaction conditions in multiple media. The antioxidant effects are determined by many factors. This review aims to discuss several important issues that should be considered for determination of experimental conditions and interpretation of experimental results in order to understand the beneficial effects and limit of antioxidants against detrimental oxidation of biological molecules. Emphasis was laid on cell culture experiments and effects of diversity of multiple oxidants on antioxidant efficacy.

Effects of hypophysectomy and subsequent FSH and testosterone treatment on inhibin production by adult rat testes

1985 ◽  
Vol 105 (1) ◽  
pp. 1-6 ◽  
Author(s):  
C. L. Au ◽  
D. M. Robertson ◽  
D. M. de Kretser
Keyword(s):  
Seminiferous Tubule ◽  
Hormonal Control ◽  
Human Chorionic Gonadotrophin ◽  
Experimental Conditions ◽  
Adult Rats ◽  
Adult Rat ◽  
Fluid Production ◽  
Tubule Fluid

ABSTRACT The hormonal control of inhibin production by adult rat testes was investigated using an in-vitro inhibin bioassay validated for the measurement of inhibin activity in charcoal-treated rat testicular extracts. The effect of hypophysectomy examined at 16 h, 3, 7 and 42 days after surgery showed a decrease in testicular inhibin content and seminiferous tubule fluid production by 7 days and a decrease in inhibin production by 42 days. Serum FSH and LH were suppressed 3 days after surgery. In 30-day chronically hypophysectomized adult rats treated for 3 days with twice daily s.c. injections of (a) human FSH (hFSH, 22 i.u./rat per day), (b) testosterone (5 mg/rat per day), (c) hFSH + testosterone (same doses as a and b), or (d) human chorionic gonadotrophin (hCG, 12 i.u./rat per day), hFSH or hFSH and testosterone stimulated an increase in testicular inhibin content but not in inhibin production or tubule fluid production. Testosterone and hCG had no effect on these parameters. It is concluded that in vivo, FSH alone stimulates an increase in testicular inhibin content. The failure to observe an increase in inhibin production in vivo is attributed to the suppression of seminiferous tubule fluid production under the same experimental conditions. J. Endocr. (1985) 105, 1–6

scholarly journals Intranasal Borna Disease Virus (BoDV-1) Infection: Insights into Initial Steps and Potential Contagiosity

2019 ◽  
Vol 20 (6) ◽  
pp. 1318 ◽  
Author(s):  
Alexandra Kupke ◽  
Sabrina Becker ◽  
Konstantin Wewetzer ◽  
Barbara Ahlemeyer ◽  
Markus Eickmann ◽  
...  
Keyword(s):  
Viral Infections ◽  
Cell Types ◽  
Nerve Fibers ◽  
Olfactory Pathway ◽  
Adult Rats ◽  
The Central Nervous System ◽  
Receptor Neurons

Mammalian Bornavirus (BoDV-1) typically causes a fatal neurologic disorder in horses and sheep, and was recently shown to cause fatal encephalitis in humans with and without transplant reception. It has been suggested that BoDV-1 enters the central nervous system (CNS) via the olfactory pathway. However, (I) susceptible cell types that replicate the virus for successful spread, and (II) the role of olfactory ensheathing cells (OECs), remained unclear. To address this, we studied the intranasal infection of adult rats with BoDV-1 in vivo and in vitro, using olfactory mucosal (OM) cell cultures and the cultures of purified OECs. Strikingly, in vitro and in vivo, viral antigen and mRNA were present from four days post infection (dpi) onwards in the olfactory receptor neurons (ORNs), but also in all other cell types of the OM, and constantly in the OECs. In contrast, in vivo, BoDV-1 genomic RNA was only detectable in adult and juvenile ORNs, nerve fibers, and in OECs from 7 dpi on. In vitro, the rate of infection of OECs was significantly higher than that of the OM cells, pointing to a crucial role of OECs for infection via the olfactory pathway. Thus, this study provides important insights into the transmission of neurotropic viral infections with a zoonotic potential.

Anionic and cationic exchange mechanisms in the skin of anurans, with special reference to Leptodactylidae in vivo

1971 ◽  
Vol 262 (842) ◽  
pp. 163-174 ◽  
Keyword(s):  
Transport Mechanism ◽  
Selective Inhibition ◽  
The Other ◽  
Sodium Absorption ◽  
Experimental Conditions ◽  
Net Flux ◽  
Cationic Exchange

In several species of anurans, the in vivo skin has been shown to absorb Na + and Cl - independently from dilute external solutions. That the mechanism for sodium absorption is different from that of chloride absroption is born out by the following: (1) Either of these ions is absorbed without an accompanying ion when this latter is impermeant. (2) From NaCl solutions there can be an unequal absorption of sodium and chloride. (3) A selective inhibition of the absorption of one of the ions can be produced experimentally, while the net flux of the other remains unchanged. In all these situations, the absorbed ion has to be exchanged against an endogenous ion of the same charge. In Calyptocephalella gayi , H + and HCO - 3 are exchanged against sodium and chloride respectively. A comparison of the relationships between H + excretion and Na + absorption in vivo skins and shortcircuited in vitro skins shows that in the latter no H + excretion occurs, only the Na + transport being maintained under these experimental conditions. From this, one must conclude that the active Na + transport is the motive factor of the transport mechanism. H + excretion by the in vivo skin plays the role of physiologically short-circuiting the Na + transport.

scholarly journals The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies

2002 ◽  
Vol 174 (1) ◽  
pp. 121-125 ◽  
Author(s):  
TM Ortiga-Carvalho ◽  
KJ Oliveira ◽  
BA Soares ◽  
CC Pazos-Moura
Keyword(s):  
Fold Increase ◽  
Adult Rats ◽  
Fed State ◽  
Rat Pituitary ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Thyroid Axis

Leptin has been shown to stimulate the hypothalamus-pituitary-thyroid axis in fasting rodents; however, its role in thyroid axis regulation under physiological conditions is still under investigation. Here it was investigated in freely fed rats whether leptin modulates thyrotroph function in vivo and whether leptin has direct pituitary effects on TSH release. Since leptin is produced in the pituitary, the possibility was also investigated that leptin may be a local regulator of TSH release. TSH was measured by specific RIA. Freely fed adult rats 2 h after being injected with a single s.c. injection of 8 microg leptin/100 g body weight showed a 2-fold increase in serum TSH (P<0.05). Hemi-pituitary explants incubated with 10(-9) and 10(-7) M leptin for 2 h showed a reduced TSH release of 40 and 50% respectively (P<0.05). Conversely, incubation of hemi-pituitary explants with antiserum against leptin, aiming to block the action of locally produced leptin, resulted in higher TSH release (45%, P<0.05). In conclusion, also in the fed state, leptin has an acute stimulatory effect on TSH release in vivo, acting probably at the hypothalamus. However, the direct pituitary effect of leptin is inhibitory and data also provide evidence that in the rat pituitary leptin may act as an autocrine/paracrine inhibitor of TSH release.

scholarly journals SMAD1/5 Signaling in the Early Equine Placenta Regulates Trophoblast Differentiation and Chorionic Gonadotropin Secretion

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 3054-3064 ◽  
Author(s):  
Victoria Cabrera-Sharp ◽  
Jordan E. Read ◽  
Stephanie Richardson ◽  
Alycia A. Kowalski ◽  
Douglas F. Antczak ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Trophoblast Cells ◽  
Rt Pcr ◽  
Trophoblast Differentiation ◽  
Gonadotropin Secretion ◽  
Morphogenetic Protein ◽  
Dose Dependent

TGFβ superfamily proteins, acting via SMAD (Sma- and Mad-related protein)2/3 pathways, regulate placental function; however, the role of SMAD1/5/8 pathway in the placenta is unknown. This study investigated the functional role of bone morphogenetic protein (BMP)4 signaling through SMAD1/5 in terminal differentiation of primary chorionic gonadotropin (CG)-secreting trophoblast. Primary equine trophoblast cells or placental tissues were isolated from day 27–34 equine conceptuses. Detected by microarray, RT-PCR, and quantitative RT-PCR, equine chorionic girdle trophoblast showed increased gene expression of receptors that bind BMP4. BMP4 mRNA expression was 20- to 60-fold higher in placental tissues adjacent to the chorionic girdle compared with chorionic girdle itself, suggesting BMP4 acts primarily in a paracrine manner on the chorionic girdle. Stimulation of chorionic girdle-trophoblast cells with BMP4 resulted in a dose-dependent and developmental stage-dependent increase in total number and proportion of terminally differentiated binucleate cells. Furthermore, BMP4 treatment induced non-CG-secreting day 31 chorionic girdle trophoblast cells to secrete CG, confirming a specific functional response to BMP4 stimulation. Inhibition of SMAD2/3 signaling combined with BMP4 treatment further enhanced differentiation of trophoblast cells. Phospho-SMAD1/5, but not phospho-SMAD2, expression as determined by Western blotting was tightly regulated during chorionic girdle trophoblast differentiation in vivo, with peak expression of phospho-SMAD1/5 in vivo noted at day 31 corresponding to maximal differentiation response of trophoblast in vitro. Collectively, these experiments demonstrate the involvement of BMP4-dependent pathways in the regulation of equine trophoblast differentiation in vivo and primary trophoblast differentiation in vitro via activation of SMAD1/5 pathway, a previously unreported mechanism of TGFβ signaling in the mammalian placenta.

scholarly journals Direct stimulatory effect of ghrelin on pituitary release of LH through a nitric oxide-dependent mechanism that is modulated by estrogen

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1223-1232 ◽  
Author(s):  
Rafael Fernández-Fernández ◽  
Manuel Tena-Sempere ◽  
Juan Roa ◽  
Juan Manuel Castellano ◽  
Víctor M Navarro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reproductive Function ◽  
Female Rats ◽  
Experimental Conditions ◽  
Gonadotropin Secretion ◽  
Minimal Effective Dose ◽  
Gh Secretion ◽  
Lh Secretion

Ghrelin, a gut peptide with key actions on food intake and GH secretion, has been recently recognized as potential regulator of reproductive function. Thus, in adult female rats, ghrelin has been proven to modulate GnRH/LH secretion, with predominant inhibitory effectsin vivo. We analyze herein potential direct pituitary effects of ghrelin on basal and GnRH-stimulated gonadotropin secretion in prepubertal female rats, and its interplay with ovarian inputs, nitric oxide (NO), and hypothalamic differentiation. In the experimental setting, pituitaries from intact and ovariectomized prepubertal female rats were challenged with ghrelinin vitroand LH secretion was monitored. Our results demonstrate that 1) ghrelin consistently stimulatedin vitropituitary LH secretion under different experimental conditions; 2) the sensitivity to ghrelin, expressed either as the minimal effective dose or the amplitude of the LH response, was modulated by ovarian inputs; 3) the blockade of estrogen action significantly augmented the stimulatory effect of ghrelin; 4) the stimulatory effect of ghrelin on LH secretion required proper NO synthesis; and 5) the ability of ghrelin to elicit LH secretionin vitrowas preserved after alteration (masculinization) of brain sexual differentiation. Overall, our present data reinforce the concept that ghrelin participates in the control of LH secretion, with potential stimulatory actions at the pituitary level that require the presence of NO and are modulated by ovarian signals.

Interaction of Measles Virus Vectors with Auger Electron Emitting Radioisotopes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5525-5525
Author(s):  
David Dingli ◽  
Kah-Whye Peng ◽  
Mary E. Harvey ◽  
Sompong Vongpunsawad ◽  
Elizabeth R. Bergert ◽  
...  
Keyword(s):  
Measles Virus ◽  
Auger Electron ◽  
Viral Vectors ◽  
Soluble Form ◽  
Sodium Iodide Symporter ◽  
Experimental Conditions ◽  
Oncolytic Activity

Abstract Background: Viral vectors based on the Edmonston strain of measles virus (MV-Edm) selectively destroy all tumor cell lines tested in vitro. The oncolytic activity of the virus is enhanced by expression of the thyroidal sodium iodide symporter (MV-NIS) that allows selective 131I uptake by infected tumor cells and eliminates myeloma tumor xenografts that are resistant to the parent virus. MV-NIS is being considered for therapy of patients with relapsed or refractory multiple myeloma. Advanced myeloma is associated with significant immunosuppression with the potential risk of uncontrolled virus proliferation. The number of agents with activity against MV is limited. Low energy (Auger) electrons have a short path length and selectively damage cells in which the isotope decays. Thus, we hypothesized that the Auger electron emitting isotope 125I, selectively taken up by cells expressing NIS, can be used to control viral proliferation. Methods: A replication competent MV that expressed both a soluble form of carcinoembryonic antigen (CEA) and NIS (MV-NICE) was rescued and characterized. Cells were infected with MV-NICE or control vectors and exposed to 125I with appropriate controls. CEA expression and viral titers were determined at different time points. The role of free radical generation on virus replication was explored. In vivo control of MV-NICE replication with 125I was attempted. Results: MV-NICE replication in vitro is inhibited by the selective uptake of 125I by cells expressing NIS. Extracellular decay of the isotope has no effect on virus proliferation. Auger electron damage is in part mediated by free radicals and abrogated by glutathione. In myeloma xenografts, control of MV-NICE with 125I was not possible under the conditions of the experiment. Conclusion: MV-NICE does not replicate faster in the presence of radiation under our experimental conditions. Auger electron emitting isotopes effectively stop propagation of MV vectors expressing NIS in vitro. Additional work is necessary to translate these observations in vivo.

scholarly journals SUN-266 Protein Induced Pancreatic Hormone Secretion Is Modulated by Vagal CaSR

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Mariana Norton ◽  
Simon C Cork ◽  
Aldara Martin Alonso ◽  
Anna G Roberts ◽  
Yateen S Patel ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hormone Secretion ◽  
Sensory Information ◽  
Glucagon Secretion ◽  
Vagal Afferents ◽  
Acid Uptake

Abstract The existence of a vago-vagal entero-pancreatic pathway, where sensory information from the gut can signal via vagal afferents to the brain to mediate changes in pancreatic function, has been recognised for over a century, and investigated extensively with regards to pancreatic exocrine secretions. However, the role of such pathways in pancreatic endocrine secretions has received less attention. The secretion of insulin and glucagon in response to protein and amino acids is conserved across species. This effect is thought to promote amino acid uptake into tissues without concomitant hypoglycaemia. We found that the essential amino acid L-Phenylalanine potently stimulates glucagon secretion, even when administered directly into the gut at small doses unlikely to significantly raise systematic levels. Administration of L-Phenylalanine also increased neuronal activation in the rat and mouse dorsal vagal complex, the central nervous system region directly innervated by vagal afferents. L-Phenylalanine modulates the activity of the calcium sensing receptor (CaSR), a nutrient sensor more commonly known for its role in calcium homeostasis, but which is thought to also act as a sensor of aromatic amino acids. Interestingly, the CaSR is one of the few nutrient sensors expressed in vagal afferents and in vitro calcium imaging revealed CaSR synthetic agonists activate subpopulations of vagal afferents. The role of CaSR in vivo was investigated further by selectively knocking down the CaSR in vagal afferents. Briefly, CaSR floxed mice were bilaterally injected directly into the nodose ganglion, where the cell bodies of vagal afferents are located, with a cre expressing adeno-associated virus. CaSR knockdown did not interfere with normal food intake, nor the vagal-dependent anorectic effects of cholecystokinin, or of L-Phenylalanine. However, it did blunt protein-induced glucagon secretion, suggesting involvement of the CaSR in the vagus nerve in protein sensing and glucose homeostasis. Future studies are required to determine the importance of vagal CaSR in protein induced pancreatic endocrine secretions, and the possibility of exploiting this circuit to develop new anti-diabetic therapies.

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