Nesfatin-1-like peptide suppresses hypothalamo–pituitary–gonadal mRNAs, gonadal steroidogenesis, and oocyte maturation in fish†

2020 ◽  
Vol 103 (4) ◽  
pp. 802-816
Author(s):  
Jithine Jayakumar Rajeswari ◽  
Azadeh Hatef ◽  
Suraj Unniappan
Keyword(s):  
Oocyte Maturation ◽  
Reproductive Hormones ◽  
Reproductive Physiology ◽  
Biologically Active ◽  
Metabolic Effects ◽  
Steroidogenic Enzyme ◽  
Male Fish ◽  
Brain Aromatase ◽  
Circulating Levels ◽  
Receptor Mrnas

Abstract Nucleobindin (Nucb)-1 and Nucb2 are DNA and Ca2+ binding proteins with multiple functions in vertebrates. Prohormone convertase-mediated processing of Nucb2 results in the production of biologically active nesfatin-1. Nesfatin-1 is involved in the regulation of reproduction in many vertebrates, including fish. Our lab originally reported a nesfatin-1-like peptide (Nlp) encoded in Nucb1 that exhibits nesfatin-1-like metabolic effects. We hypothesized that Nlp has a suppressive role in the reproductive physiology of fish. In this research, whether Nlp regulates reproductive hormones and oocyte maturation in fish were determined. Single intraperitoneal (IP) injection of goldfish Nlp (50 ng/g body weight) suppressed salmon and chicken gonadotropin-releasing hormone (sgnrh and cgnrh2), gonadotropin-inhibiting hormone (gnih) and its receptor (gnihr), and kisspeptin and brain aromatase mRNA expression in the hypothalamus of both male and female goldfish. In the pituitary, Nlp decreased mRNAs encoding lhb, fshb and kisspeptin and its receptor, while a significant increase in gnih and gnihr was observed. In the gonads, lh (only in male fish) and fsh receptor mRNAs were also significantly downregulated in Nlp-injected fish. Sex-specific modulation of gnih, gnihr, and kisspeptin system in the gonads was also observed. Nlp decreased sex steroidogenic enzyme encoding mRNAs and circulating levels of testosterone and estradiol. In addition, incubation of zebrafish ovarian follicles with Nlp resulted in a reduction in oocyte maturation. These results provide evidence for a robust role for Nlp in regulating reproductive hormones in goldfish and oocyte maturation in zebrafish, and these effects resemble that of nesfatin-1.

scholarly journals Acute Effects of Glucagon on Reproductive Hormone Secretion in Healthy Men

2020 ◽  
Vol 105 (6) ◽  
pp. 1899-1905
Author(s):  
Chioma Izzi-Engbeaya ◽  
Sophie Jones ◽  
Yoshibye Crustna ◽  
Pratibha C Machenahalli ◽  
Deborah Papadopoulou ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Reproductive Hormones ◽  
Metabolic Effects ◽  
Acute Administration ◽  
Reproductive Hormone ◽  
Glucagon Receptor ◽  
Healthy Men ◽  
Testosterone Levels ◽  
Reproductive Axis ◽  
Lh Pulsatility

Abstract Context Glucagon increases energy expenditure; consequently, glucagon receptor agonists are in development for the treatment of obesity. Obesity negatively affects the reproductive axis, and hypogonadism itself can exacerbate weight gain. Therefore, knowledge of the effects of glucagon receptor agonism on reproductive hormones is important for developing therapeutics for obesity; but reports in the literature about the effects of glucagon receptor agonism on the reproductive axis are conflicting. Objective The objective of this work is to investigate the effect of glucagon administration on reproductive hormone secretion in healthy young men. Design A single-blinded, randomized, placebo-controlled crossover study was conducted. Setting The setting of this study was the Clinical Research Facility, Imperial College Healthcare NHS Trust. Participants Eighteen healthy eugonadal men (mean ± SEM: age 25.1 ± 1.0 years; body mass index 22.5 ± 0.4 kg/m2; testosterone 21.2 ± 1.2 nmol/L) participated in this study. Intervention An 8-hour intravenous infusion of 2 pmol/kg/min glucagon or rate-matched vehicle infusion was administered. Main Outcome Measures Luteinizing hormone (LH) pulsatility; LH, follicle-stimulating hormone (FSH), and testosterone levels were measured. Results Although glucagon administration induced metabolic effects (insulin area under the curve: vehicle 1065 ± 292 min.µU/mL vs glucagon 2098 ± 358 min.µU/mL, P < .001), it did not affect LH pulsatility (number of LH pulses/500 min: vehicle 4.7 ± 0.4, glucagon 4.2 ± 0.4, P = .22). Additionally, there were no significant differences in circulating LH, FSH, or testosterone levels during glucagon administration compared with vehicle administration. Conclusions Acute administration of a metabolically active dose of glucagon does not alter reproductive hormone secretion in healthy men. These data are important for the continued development of glucagon-based treatments for obesity.

scholarly journals Clinical and Metabolic Effects of Alpha-Lipoic Acid Associated with Two Different Doses of Myo-Inositol in Women with Polycystic Ovary Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Franca Fruzzetti ◽  
Elena Benelli ◽  
Tiziana Fidecicchi ◽  
Massimo Tonacchera
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Lipoic Acid ◽  
Polycystic Ovary ◽  
Insulin Response ◽  
Reproductive Hormones ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Ovary Syndrome ◽  
Before And After ◽  
Different Doses

The aim of this retrospective study was to evaluate the effects of a treatment with α-lipoic acid (ALA) associated with two different doses of myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Eighty-eight women received the treatment, and 71 among them had complete clinical charts and were considered eligible for this study. All women were treated with 800 mg of ALA per day: 43 patients received 2000 mg of MI and 28 received 1000 mg of MI per day. Menstrual cyclicity, BMI, FSH, LH, estradiol, testosterone, androstenedione, fasting insulin, HOMA-IR, and insulin response to a 2 h OGTT were evaluated before and after 6 months of treatment. The presence of diabetic relatives (DRs) was investigated. Cycle regularity was improved in 71.2% of women. The improvement of menstrual cyclicity occurred regardless of the state of IR and the presence of DRs of the patients. Women with IR mainly showed a significant improvement of metabolic parameters, while those without IR had significant changes of reproductive hormones. Patients with DRs did not show significant changes after the treatment. 85.7% of women taking 2000 mg of MI reported a higher improvement of menstrual regularity than those taking 1000 mg of MI (50%; p<0.01). In conclusion, ALA + MI positively affects the menstrual regularity of women with PCOS, regardless of their metabolic phenotype, with a more evident effect with a higher dose of MI. This effect seems to be insulin independent. The presence of IR seems to be a predictor of responsivity to the treatment in terms of an improvement of the metabolic profile.

scholarly journals Circulating levels of biologically active parathyroid hormone in rheumatic diseases.

1982 ◽  
Vol 41 (6) ◽  
pp. 569-573 ◽  
Author(s):  
J Dunham ◽  
B E Bourke ◽  
L Bitensky ◽  
J Chayen ◽  
N Loveridge ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Rheumatic Diseases ◽  
Biologically Active ◽  
Circulating Levels

Leptin treatment markedly increased plasma adiponectin but barely decreased plasma resistin of ob/ob mice

2004 ◽  
Vol 287 (3) ◽  
pp. E446-E453 ◽  
Author(s):  
Marie-Laure Delporte ◽  
Samira Ait El Mkadem ◽  
Muriel Quisquater ◽  
Sonia M. Brichard
Keyword(s):  
Gene Expression ◽  
Protein Production ◽  
Subcutaneous Fat ◽  
Metabolic Effects ◽  
Obese Mice ◽  
Direct Stimulation ◽  
Plasma Adiponectin ◽  
Circulating Levels ◽  
Fat Pads ◽  
Stimulation Of

Adiponectin (ApN) and leptin are two adipocytokines that control fuel homeostasis, body weight, and insulin sensitivity. Their interplay is still poorly studied. These hormones are either undetectable or decreased in obese, diabetic ob/ob mice. We examined the effects of leptin treatment on ApN gene expression, protein production, secretion, and circulating levels of ob/ob mice. We also briefly tackled the influence of this treatment on resistin, another adipocytokine involved in obesity-related insulin resistance. Leptin-treated (T) obese mice (continuous sc infusion for 6 days) were compared with untreated lean (L), untreated obese (O), and untreated pair-fed obese (PF) mice. Blood was collected throughout the study. At day 3 or day 6, fat pads were either directly analyzed (mRNA, ApN content) or cultured for up to 24 h (ApN secretion). The direct effect of leptin was also studied in 3T3-F442A adipocytes. Compared with L mice, ApN content of visceral or subcutaneous fat and ApN secretion by adipose explants were blunted in obese mice. Accordingly, plasma ApN levels of O mice were decreased by 50%. Leptin treatment of ob/ob mice increased ApN mRNAs, ApN content, and secretion from the visceral depot by 50–80%. Leptin also directly stimulated ApN mRNAs and secretion from 3T3-F442A adipocytes. After 6 days of treatment, plasma ApN of ob/ob mice increased 2.5-fold, a rise that did not occur in PF mice. Plasma resistin of T mice was barely decreased. Leptin treatment, but not mere calorie restriction, corrects plasma ApN in obese mice by restoring adipose tissue ApN concentrations and secretion, at least in part, via a direct stimulation of ApN gene expression. Such a treatment only minimally affects circulating resistin. ApN restoration could, in concert with leptin, contribute to the metabolic effects classically observed during leptin administration.

scholarly journals Nesfatin-1 suppresses fish reproductive axis and gonadal steroidogenesis

Reproduction ◽  
2020 ◽  
Vol 160 (3) ◽  
pp. 445-454
Author(s):  
Jithine Jayakumar Rajeswari ◽  
Suraj Unniappan
Keyword(s):  
Mrna Expression ◽  
Pituitary Hormones ◽  
Reproductive Hormones ◽  
Male And Female ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
Reproductive Axis ◽  
Brain Aromatase ◽  
Males And Females ◽  
Cytochrome P450 Family

Nesfatin-1 is a naturally occurring orphan ligand in fish and mammals. Research in our lab resulted in the identification of an inhibitory role for nesfatin-1 on pituitary hormones (goldfish) and oocyte maturation (zebrafish). The present study is an extension of these original findings and aimed to determine whether nesfatin-1 has any additional effects on HPG genes in male and female goldfish. We found that a single i.p. injection of synthetic nesfatin-1 (50 ng/g body weight) downregulated the expression of salmon gonadotropin-releasing hormone (sgnrh), chicken gnrh-II (cgnrh-II), kisspeptin receptor (gpr54a) and brain aromatase (cyp19a1b) mRNAs in the hypothalamus of both male and female goldfish at 15 min post-administration. In the pituitary of both males and females, nesfatin-1 reduced luteinizing hormone beta (lhβ) and follicle stimulating hormone beta (fshβ) mRNA expression at 60 min and gpr54a mRNA at 15 min. Similarly, the gonadotropin receptors lhr and fshr were downregulated in the gonads. Meanwhile, gonadotropin inhibiting hormone (gnih), gnih receptor, kisspeptin 1 (kiss1) and gpr54a mRNA expression in the gonads were increased post-nesfatin-1 treatment. Nesfatin-1 negatively influences the star, cytochrome P450 family 11 subfamily A member 1, anti-mullerian hormone and aromatase mRNAs. In agreement with these results, nesfatin-1 reduced plasma estradiol and testosterone in female and male goldfish circulation at 60 min post-injection. The information generated through this research further solidified nesfatin-1 as an inhibitor of reproductive hormones in fish. Targeting nesfatin-1 and related peptides could yield beneficial effects in fish reproduction and aquaculture.

INTERACTION OF DAILY INJECTIONS AND SUBCUTANEOUS RESERVOIRS OF MELATONIN ON THE REPRODUCTIVE PHYSIOLOGY OF FEMALE SYRIAN HAMSTERS

1979 ◽  
Vol 91 (1) ◽  
pp. 59-69 ◽  
Author(s):  
C. Trakulrungsi ◽  
R. J. Reiter ◽  
W. K. Trakulrungsi ◽  
M. K. Vaughan ◽  
P. J. Waring-Ellis
Keyword(s):  
Luteinizing Hormone ◽  
Untreated Control ◽  
Light Period ◽  
Reproductive Physiology ◽  
Pituitary Hormone ◽  
Inhibitory Effects ◽  
Syrian Hamsters ◽  
First Report ◽  
Treatment Procedures ◽  
Circulating Levels

ABSTRACT This study investigated the ability of continuously available melatonin (from sc melatonin-beeswax pellets that were implanted bi-weekly) in overcoming the antigonadotrophic action of single daily melatonin (25 μg) injections given late in the light period to female Syrian hamsters kept in light:dark cycles of 14:10. The melatonin-beeswax pellets contained either 1, 50, 500 μg, 1 or 10 mg melatonin and 25 mg beeswax. Daily melatonin injections into hamsters implanted with beeswax only caused vaginal acyclicity in 60 % of the animals within 6 weeks. After 10 weeks of treatment, uterine weights and pituitary levels of immunoreactive prolactin were still greatly depressed. Beeswax pellets containing either 500 μg, 1 or 10 mg melatonin overcame the inhibitory effects of daily melatonin injections. Thus, the vaginal cycles and pituitary hormone levels of these animals were indistinguishable from those of untreated control animals. Beeswax pellets containing either 1 or 50 μg melatonin were incapable of counteracting the antigonadotrophic effects of daily injections of melatonin. This is the first report that continuously available melatonin can negate the effects of daily injections of melatonin in female hamsters. When measured after 10 weeks, none of the treatment procedures significantly influenced circulating levels of luteinizing hormone or prolactin.

Modern concepts of the adipose tissue effect on bone metabolism regulation

2020 ◽  
Vol 18 (6) ◽  
pp. 69-72
Author(s):  
N. Yu. KRUTIKOVA ◽  
◽  
A. S. EFREMENKOVA ◽  
Keyword(s):  
Adipose Tissue ◽  
Bone Metabolism ◽  
General Circulation ◽  
The Body ◽  
Biologically Active ◽  
Metabolic Effects ◽  
Published Data ◽  
Internal Environment ◽  
Metabolism Regulation ◽  
Active Substances

At present, it has been proved that adipose tissue, in addition to storing energy, is a complex hormonally active organ. Biological active substances secreted by adipose tissue, entering the general circulation, have a variety of metabolic effects, interact with various organs and systems, in particular with bone tissue, and participate in maintaining the constancy of the body internal environment. A number of hormones secreted by adipose tissue are well studied, such as leptin, adiponectin, interleukin-6, etc., others require further research in order to study their effects on various organs and systems. The published data suggest the multidirectional effect of biologically active substances on bone metabolism. The biological activity of hormones can be increased or decreased when interacting with receptors and/or binding proteins. Lack or excess of adipose tissue leads to various metabolic disorders and a shift in the dynamic balance of the constancy of the internal environment of the body.

scholarly journals Proteome adaptations in Ethe1-deficient mice indicate a role in lipid catabolism and cytoskeleton organization via post-translational protein modifications

2013 ◽  
Vol 33 (4) ◽  
Author(s):  
Tatjana M. Hildebrandt ◽  
Ivano Di Meo ◽  
Massimo Zeviani ◽  
Carlo Viscomi ◽  
Hans-Peter Braun
Keyword(s):  
Redox Regulation ◽  
Sulfide Oxidation ◽  
Biologically Active ◽  
Protein Modifications ◽  
Cytoskeleton Organization ◽  
Ethylmalonic Encephalopathy ◽  
Signalling Molecule ◽  
Branched Chain ◽  
Cytoskeleton Dynamics ◽  
Circulating Levels

Hydrogen sulfide is a physiologically relevant signalling molecule. However, circulating levels of this highly biologically active substance have to be maintained within tightly controlled limits in order to avoid toxic side effects. In patients suffering from EE (ethylmalonic encephalopathy), a block in sulfide oxidation at the level of the SDO (sulfur dioxygenase) ETHE1 leads to severe dysfunctions in microcirculation and cellular energy metabolism. We used an Ethe1-deficient mouse model to investigate the effect of increased sulfide and persulfide concentrations on liver, kidney, muscle and brain proteomes. Major disturbances in post-translational protein modifications indicate that the mitochondrial sulfide oxidation pathway could have a crucial function during sulfide signalling most probably via the regulation of cysteine S-modifications. Our results confirm the involvement of sulfide in redox regulation and cytoskeleton dynamics. In addition, they suggest that sulfide signalling specifically regulates mitochondrial catabolism of FAs (fatty acids) and BCAAs (branched-chain amino acids). These findings are particularly relevant in the context of EE since they may explain major symptoms of the disease.

New Medicines: Potency, Selectivity and the Pill

1977 ◽  
Vol 5 (6) ◽  
pp. 141-143
Author(s):  
Michael A Bodin
Keyword(s):  
Oral Contraceptives ◽  
Biologically Active ◽  
Metabolic Effects ◽  
Intrinsic Activity ◽  
Per Se ◽  
Low Incidence ◽  
Synthetic Progestogen

The development of a selective, synthetic progestogen ought to dispel any notion that high intrinsic activity ( potency) per se is disadvantageous. Provided there is excellent cycle control with a low incidence of additional actions, the patient can only benefit long-term from the ingestion of biologically active steroids in lower quantities than were formerly available in oral contraceptives. When intrinsic activities for androgenic, oestrogenic or metabolic effects are diminished, it is difficult to conceive the disadvantages for the patient.

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