Non-genomic action of vitamin D3 on N-methyl-D-aspartate and kainate receptor-mediated actions in juvenile gonadotrophin-releasing hormone neurons

2017 ◽  
Vol 29 (6) ◽  
pp. 1231 ◽  
Author(s):  
Pravin Bhattarai ◽  
Janardhan P. Bhattarai ◽  
Min Sun Kim ◽  
Seong Kyu Han
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Critical Role ◽  
Kainate Receptor ◽  
Inward Current ◽  
Releasing Hormone ◽  
Postsynaptic Currents ◽  
Gnrh Neurons ◽  
Gonadotrophin Releasing Hormone ◽  
Spontaneous Postsynaptic Currents

Vitamin D is a versatile signalling molecule that plays a critical role in calcium homeostasis. There are several studies showing the genomic action of vitamin D in the control of reproduction; however, the quick non-genomic action of vitamin D at the hypothalamic level is not well understood. Therefore, to investigate the effect of vitamin D on juvenile gonadotrophin-releasing hormone (GnRH) neurons, excitatory neurotransmitter receptor agonists N-methyl-D-aspartate (NMDA, 30 μM) and kainate (10 μM) were applied in the absence or in the presence of vitamin D3 (VitaD3, 10 nM). The NMDA-mediated responses were decreased by VitaD3 in the absence and in the presence of tetrodotoxin (TTX), a sodium-channel blocker, with the mean relative inward current being 0.56 ± 0.07 and 0.66 ± 0.07 (P < 0.05), respectively. In addition, VitaD3 induced a decrease in the frequency of gamma-aminobutyric acid mediated (GABAergic) spontaneous postsynaptic currents and spontaneous postsynaptic currents induced by NMDA application with a mean relative frequency of 0.595 ± 0.07 and 0.56 ± 0.09, respectively. Further, VitaD3 decreased the kainate-induced inward currents in the absence and in the presence of TTX with a relative inward current of 0.64 ± 0.06 and 0.68 ± 0.06, respectively (P < 0.05). These results suggest that VitaD3 has a non-genomic action and partially inhibits the NMDA and kainate receptor-mediated actions of GnRH neurons, suggesting that VitaD3 may regulate the hypothalamic–pituitary–gonadal (HPG) axis at the time of pubertal development.

scholarly journals L-type calcium channels and MAP kinase contribute to thyrotropin-releasing hormone-induced depolarization in thalamic paraventricular nucleus neurons

2016 ◽  
Vol 310 (11) ◽  
pp. R1120-R1127 ◽  
Author(s):  
Miloslav Kolaj ◽  
Li Zhang ◽  
Leo P. Renaud
Keyword(s):  
Transient Receptor Potential ◽  
Cannabinoid Receptor ◽  
Ryanodine Receptors ◽  
Critical Role ◽  
Receptor Potential ◽  
Thyrotropin Releasing Hormone ◽  
Induced Response ◽  
Inward Current ◽  
Releasing Hormone ◽  
Intracellular Ca

In rat paraventricular thalamic nucleus (PVT) neurons, activation of thyrotropin-releasing hormone (TRH) receptors enhances neuronal excitability via concurrent decrease in a G protein-coupled inwardly rectifying K (GIRK)-like conductance and opening of a cannabinoid receptor-sensitive transient receptor potential canonical (TRPC)-like conductance. Here, we investigated the calcium (Ca2+) contribution to the components of this TRH-induced response. TRH-induced membrane depolarization was reduced in the presence of intracellular BAPTA, also in media containing nominally zero [Ca2+]o, suggesting a critical role for both intracellular Ca2+ release and Ca2+ influx. TRH-induced inward current was unchanged by T-type Ca2+ channel blockade, but was decreased by blockade of high-voltage-activated Ca2+ channels (HVACCs). Both the pharmacologically isolated GIRK-like and the TRPC-like components of the TRH-induced response were decreased by nifedipine and increased by BayK8644, implying Ca2+ influx via L-type Ca2+ channels. Only the TRPC-like conductance was reduced by either thapsigargin or dantrolene, suggesting a role for ryanodine receptors and Ca2+-induced Ca2+ release in this component of the TRH-induced response. In pituitary and other cell lines, TRH stimulates MAPK. In PVT neurons, only the GIRK-like component of the TRH-induced current was selectively decreased in the presence of PD98059, a MAPK inhibitor. Collectively, the data imply that TRH-induced depolarization and inward current in PVT neurons involve both a dependency on extracellular Ca2+ influx via opening of L-type Ca2+ channels, a sensitivity of a TRPC-like component to intracellular Ca2+ release via ryanodine channels, and a modulation by MAPK of a GIRK-like conductance component.

scholarly journals Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice

2020 ◽  
Vol 21 (17) ◽  
pp. 5991
Author(s):  
Santosh Rijal ◽  
Dong Hyu Cho ◽  
Seon-Ah Park ◽  
Seon Hui Jang ◽  
István M. Ábrahám ◽  
...  
Keyword(s):  
Pertussis Toxin ◽  
Gonadotropin Releasing Hormone ◽  
Kainate Receptors ◽  
Kainate Receptor ◽  
Induced Response ◽  
Na Channel ◽  
Releasing Hormone ◽  
Plasma Melatonin ◽  
Gnrh Neurons ◽  
Physiologic Regulation

Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic–pituitary–gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na+ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors.

scholarly journals Study of association between hypovitminosis D and fibroid uterus

2021 ◽  
Vol 10 (6) ◽  
pp. 2432
Author(s):  
Sangeeta Chowdhary ◽  
Mala Shukla ◽  
Ruchi Joshi
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Financial Burden ◽  
Critical Role ◽  
Serum Vitamin ◽  
P Value ◽  
Vitamin D Receptors ◽  
Fibroid Uterus ◽  
Vitamin D Levels ◽  
Prospective Longitudinal

Background: Fibroid uterus or leiomyoma is a benign tumour composed mainly of unicellular smooth muscle cells with varying amounts of fibrous connective tissue. UF are associated with significant morbidity as it presents in form of abnormal uterine bleeding, anaemia, pelvic pain, subfertility, and obstetric complications and causes financial burden on the patient. Recent studies have shown the critical role that vitamin D plays in fibroid formation, with individual fibroids expressing lower levels of vitamin D receptors than adjacent healthy tissue, making vitamin D deficiency a crucial, yet preventable risk factor.Methods: This was cross-sectional observational study. It was conducted on 140 female patients aged (18 to 50 years) presenting to the OPD of department of obstetrics and gynecology at NDMC & Hindu Rao Hospital during July 2019 to June 2020. 70 women had uterine fibroids on ultrasound and treated as cases and rest healthy women without fibroids served as controls. All women were subjected to ultrasound examination of uterus followed by serum vitamin D3 levels.Results: The mean value of vitamin D levels in cases was 12.81±8.56 ng/ml and in controls it was 19.83±9.21 ng/ml with p value<0.0001. Thus, it was statistically significant lower in cases of fibroid uterus as compared to controls. Secondary incidental outcomes were found between vitamin D3 level and BMI as fibroids occur statistically significantly more often in patient having of BMI ≥25 kg/m2. Also, menorrhagia and dysmenorrhea were the major complaints in 62.5% of cases followed by lowers abdominal pain and dyspareunia.Conclusions: Our study reached significance in the inverse correlation between fibroids and vitamin D levels at the primary outcome level. Larger prospective longitudinal studies drawing on more number and eliminating confounding variables are needed.

Neurophysiological control of the secretion of gonadotrophin-releasing hormone and luteinizing hormone in the sheep--a review

1991 ◽  
Vol 3 (2) ◽  
pp. 137 ◽  
Author(s):  
JC Thiery ◽  
GB Martin
Keyword(s):  
Luteinizing Hormone ◽  
Steroid Receptors ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Neural Pathways ◽  
Releasing Hormone ◽  
Diagonal Band ◽  
Gonadotrophin Secretion ◽  
Gnrh Neurons ◽  
Gonadotrophin Releasing Hormone

The anterior pituitary gland secretes pulses of luteinizing hormone (LH) in response to pulses of gonadotrophin-releasing hormone (GnRH) released into the hypophysial portal blood by the hypothalamus. The pulsatile nature of the secretions is very important because the frequency of the pulses is directly related to the activity of the GnRH neurons. We can therefore take advantage of this phenomenon to develop mechanistic interpretations of responses to experimental treatments designed to unravel the neural pathways that influence what is, arguably, the most important individual signal controlling the activity of the reproductive system. We might also resolve the disagreements in the literature covering the neuropharmacology of gonadotrophin secretion. In this review, we describe work towards this end in the sheep. Most (95%) of the 2500 GnRH cell bodies in the sheep brain are located in a region covering the anterior hypothalamus, the medial preoptic area, the diagonal band of Broca, and the septum. The axons of up to 50% of these cells terminate in the organum vasculosum of the lamina terminalis. The remainder terminate in the median eminence and form the final common pathway for the many factors that affect gonadotrophin secretion. Among the factors known to affect the frequency of the pulses (or the activity of the GnRH neurons) are nutrition, pheromones, photoperiod and gonadal steroids (negative and positive feedback). Factors that affect GnRH pulse amplitude are more difficult to determine because variations in pituitary responsiveness prevent the use of LH patterns as a 'bioassay'. Techniques developed recently have allowed the direct measurement of GnRH pulse amplitude and revealed inhibitory effects of oestradiol, but we do not know whether this effect is due to a reduction in the amount of GnRH released by each neurone or a reduction in the number of neurones releasing a pulse. It is unlikely that the factors that alter pulse frequency do so by directly affecting the GnRH cells. For example, it is obvious that other cells, with specific receptors for pheromonal or nutritional stimuli, formulate a signal that is transferred to the GnRH cells via interneurones. Similarly, it is likely that a hypothalamic clock intervenes between photoperiodic inputs and GnRH output. Opioidergic neurons have been proposed as a link in this system, but the complexity of their action makes it unlikely that they directly affect the GnRH neurons. The responses to steroids are simple and rapid, but steroid receptors have not been found in GnRH cells, so at least one other set of interneurones is involved.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Vitamins D2 and D3 have overlapping but different effects on human gene expression revealed through analysis of blood transcriptomes in a randomised double-blind placebo-controlled food-fortification trial

2021 ◽  
Author(s):  
Louise Durrant ◽  
Giselda Bucca ◽  
Andrew Hesketh ◽  
Carla Moller-Levet ◽  
Laura Tripkovic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Human Physiology ◽  
Vitamin D3 ◽  
Biological Effects ◽  
Controlled Trial ◽  
Critical Role ◽  
Vitamin D2 ◽  
Double Blind

Abstract For the first time we report the relative influences of vitamin D2 and vitamin D3 on genome-wide gene expression in whole blood from healthy women, representing two ethnic groups, white European and South Asian. In this randomised placebo-controlled trial, participants were given daily physiological doses (15 µg) of either vitamin D2 or D3 for 12 weeks and changes in the transcriptome were compared relative to the transcriptome at baseline. While there was some overlap in the repertoire of differentially expressed genes after supplementation with each vitamin D source, most changes were specific to either vitamin D3 or vitamin D2, suggesting that each form of the vitamin may have different effects on human physiology. Notably, following vitamin D3 supplementation, the majority of changes in gene expression reflected a down-regulation in the activity of genes, many encoding components of the innate and adaptive immune systems. These are consistent with the emerging concept that vitamin D orchestrates a shift in the immune system towards a more tolerogenic status. Moreover, gene expression associated with type 1 and type 2 interferon activity differed following supplementation with either vitamin D2 or vitamin D3, with only vitamin D3 having a stimulatory effect. Interferons play a critical role in the innate response to infection and aberrant type 1 interferon signalling has recently been implicated in severe Covid-19 disease. The observed differences in gene expression after supplementation with vitamin D2 compared with vitamin D3 warrant a more intensive investigation of the biological effects of the two forms of vitamin D on human physiology.

Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial

2020 ◽  
pp. 1-10
Author(s):  
Giuseppe Derosa ◽  
Angela D’Angelo ◽  
Chiara Martinotti ◽  
Maria Chiara Valentino ◽  
Sergio Di Matteo ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Metabolic Control ◽  
Vitamin D3 ◽  
Therapy Group ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Abstract. Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p < 0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p = 0.037, p = 0.048, and p = 0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p = 0.031, p = 0.037, and p = 0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.

Vitamin-D-Effekte auf Komponenten des kardiovaskulären Risikos

2011 ◽  
Vol 20 (04) ◽  
pp. 314-319
Author(s):  
H. Sourij ◽  
H. Dobnig
Keyword(s):  
Vitamin D ◽  
Vitamin D3

ZusammenfassungGroße Beobachtungsstudien legen einen Zusammenhang zwischen Vitamin-D-Mangel und kardiovaskulärem Risiko bis hin zur Mortalität nahe. Manche Beobachtungen werden auch durch präklinische Studienergebnisse unterstützt. Für praktisch alle wichtigen kardiovaskulären Endpunkte fehlen heute jedoch Ergebnisse randomisierter und ausreichend langer durchgeführter Studien. Der Vitamin-D-Mangel ist ebenso wie andere Risikofaktoren für Herzkreislauf-Erkrankung äußerst prävalent, so dass auch kleinere Effekte theoretisch große Bedeutung für die Volksgesundheit haben könnten. Die DVO-Leitlinien empfehlen eine Vitamin-D-Gabe von 800–2000 IE Vitamin D3 täglich. Damit können nachteilige muskuloskelettale Effekte erwiesenermaßen vermieden und gleichzeitig auch mögliche kardiovaskuläre Vorteile erzielt werden.

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