scholarly journals Exposure of Xenopus laevis tadpoles to finasteride, an inhibitor of 5-α reductase activity, impairs spermatogenesis and alters hypophyseal feedback mechanisms

2009 ◽  
Vol 43 (5) ◽  
pp. 209-219 ◽  
Author(s):  
R Urbatzka ◽  
B Watermann ◽  
I Lutz ◽  
W Kloas
Keyword(s):  
Xenopus Laevis ◽  
Reductase Activity ◽  
Gonadal Development ◽  
Transient Effects ◽  
Feedback Mechanisms ◽  
Sexual Steroids ◽  
Chain Cleavage ◽  
Female Brain ◽  
Short Term Exposure ◽  
Cleavage Enzyme

Sexual steroids have major regulatory functions in gonadal development, maturation of gametes and sexual differentiation in vertebrates. Previous studies in amphibians provided evidence that dihydrotestosterone and activity of 5-α reductases might play a significant role in androgen-mediated reproductive biology. To test the involvement of 5-α reductases in maturation of gametes in amphibians, Xenopus laevis was exposed to finasteride (FIN), a known inhibitor of 5-α reductase enzyme activity. In a long-term exposure from stage 46 to 66, severe disruption of spermatogenesis was observed in histological analysis of testes as detected by occurrence of empty spermatocysts, while ovaries remained unaffected. Real-time PCR analyses of male and female brain revealed an increase of LHβ mRNA and a decrease of FSHβ mRNA in males, suggesting a signalling on testes that could result in increased steroidogenesis and reduced Sertoli cell proliferation. Accordingly, the mRNA expression of P450 side chain cleavage enzyme and 5-α reductase type 2 was increased in testes, while no effects could be observed on steroidogenic genes in ovaries. A short-term exposure to testosterone, FIN and testosterone+FIN showed that transient effects of FIN targeted males selectively and, in particular, interfered with the hypothalamus–pituitary–gonad axis. Furthermore, a negative feedback of testosterone on LHβ was observed on males and females. This study provides evidence that exposure of X. laevis to FIN, an inhibitor of 5-α reductases, impaired spermatogenesis and involved sex-specific hypophyseal feedback mechanisms.

P450 side-chain cleavage enzyme autoantibodies in canine Addison's disease

2013 ◽  
pp. 1-1
Author(s):  
Alisdair Boag ◽  
Kerry McLaughlin ◽  
Mike Christie ◽  
Peter Graham ◽  
Harriet Syme ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Side Chain ◽  
Addison's Disease ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

Comparison of the immunochemical properties of human placental and bovine adrenal cholesterol side-chain cleavage enzyme complex

1989 ◽  
Vol 998 (2) ◽  
pp. 189-195 ◽  
Author(s):  
Sergei A. Usanov ◽  
Paavo Honkakoski ◽  
Matti A. Lang ◽  
Markku Pasanen ◽  
Olavi Pelkonen ◽  
...  
Keyword(s):  
Side Chain ◽  
Enzyme Complex ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

scholarly journals Status of the down-regulated canine testis using two different GNRH agonist implants in comparison with the juvenile testis

Reproduction ◽  
2013 ◽  
Vol 146 (6) ◽  
pp. 517-526 ◽  
Author(s):  
S Goericke-Pesch ◽  
M Gentil ◽  
A Spang ◽  
M P Kowalewski ◽  
K Failing ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Gnrh Agonist ◽  
Sertoli Cells ◽  
Protein Level ◽  
Limit Of Detection ◽  
Mrna Level ◽  
Cell Nuclei ◽  
Chain Cleavage ◽  
Cleavage Enzyme

Testicular function in the dog was down-regulated using two different GNRH agonist implants, with adult and juvenile testes serving as controls. Treatment resulted in an increased percentage of the interstitial area and decreased area of Leydig cell nuclei. Expression of StAR and the steroidogenic enzymes cytochrome P450 side-chain cleavage enzyme (P450scc, CYP11A1) and cytochrome P450 17α-hydroxylase-17,20-lyase (P450c17, CYP17A1) in Leydig cells was blocked at the mRNA and protein level, showing no differences between the two agonists. Staining for androgen receptor (AR) by immunohistochemistry was positive in Sertoli, Leydig and peritubular cells and some spermatogonia, with in situ hybridization confirming expression in Sertoli cells. At the mRNA level, expression of AR was not affected; however, translation was blocked (reduced percentage of AR-positive Sertoli cells), with the number of nuclei in basal position being decreased. In the juvenile testes, mRNA expression of StAR, CYP11A1 and CYP17A1 was higher compared with the other groups but distinctly lower for the AR. At the protein level, the expression was at the limit of detection for StAR; AR-positive Sertoli cells were not detected. Our observations show that the down-regulated testis is different from the juvenile one rather resembling the testicular status in seasonal breeders out of season.

scholarly journals Resveratrol Stimulates Cortisol Biosynthesis by Activating SIRT-Dependent Deacetylation of P450scc

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3258-3268 ◽  
Author(s):  
Donghui Li ◽  
Eric B. Dammer ◽  
Marion B. Sewer
Keyword(s):  
Protein Expression ◽  
Fold Increase ◽  
Pyridine Nucleotide ◽  
Nucleotide Metabolism ◽  
Side Chain ◽  
Mitochondrial Enzyme ◽  
Adrenocortical Cells ◽  
Protein Levels ◽  
Chain Cleavage ◽  
Cleavage Enzyme

In the human adrenal cortex, cortisol is synthesized from cholesterol by members of the cytochrome P450 superfamily and hydroxysteroid dehydrogenases. Both the first and last steps of cortisol biosynthesis occur in mitochondria. Based on our previous findings that activation of ACTH signaling changes the ratio of nicotinamide adenine dinucleotide (NAD) phosphate to reduced NAD phosphate in adrenocortical cells, we hypothesized that pyridine nucleotide metabolism may regulate the activity of the mitochondrial NAD+-dependent sirtuin (SIRT) deacetylases. We show that resveratrol increases the protein expression and half-life of P450 side chain cleavage enzyme (P450scc). The effects of resveratrol on P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5 expression. Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis. Finally, resveratrol also increases the protein expression of P450 11β, another mitochondrial enzyme required for cortisol biosynthesis. Collectively, this study identifies a role for NAD+-dependent SIRT deacetylase activity in regulating the expression of mitochondrial steroidogenic P450.

scholarly journals Impacts of three glyphosate formulations on gonadal development of Xenopus laevis

2021 ◽  
Vol 5 ◽  
pp. 239784732110314
Author(s):  
Oluwaseun O Babalola ◽  
J Christoff Truter ◽  
Johannes H van Wyk
Keyword(s):  
Xenopus Laevis ◽  
Body Mass ◽  
Reproductive System ◽  
Sex Ratios ◽  
Gonadal Development ◽  
Application Rate ◽  
Amphibian Declines ◽  
The Body ◽  
Pesticide Pollution ◽  
Glyphosate Formulations

The emergence of widespread morphological malformations in the reproductive system of wildlife is generating increasing concerns. This concern is because the observed malformities may be linked to pollution by pesticides and other chemicals. The amphibian declines, for example, have been linked to pesticide pollution among other factors. Using an extended Xenopus Metamorphosis Assay protocol, until the tadpoles metamorphosized, the exposure impacts of three glyphosate formulations, namely, Roundup, Kilo Max and Enviro Glyphosate, were assessed on the reproductive system of Xenopus laevis, vis-a-vis the body mass, sex ratios and morphological malformations as endpoints. The exposure concentrations ranged between 0.2–0.6 mg/L, 0.9–28 mg/L and 90–280 mg/L for Roundup, Enviro Glyphosate, and Kilo Max, respectively. Both Kilo Max and Enviro Glyphosate formulations significantly reduced the body mass of the metamorphs compared to the control. In sex ratios, only Kilo Max altered the percentage sex ratio of the treated frogs at a ratio of 68:32 (F:M) compared to 50:50 ratio in the control. In reproductive malformations, the three formulations showed abnormality index range of 22.3–49%, 17.5–37.5% and 20–30% for the Kilo Max, Enviro Glyphosate and Roundup formulations, respectively, compared to 7.5% in the control. Observed reproductive malformations include mixed sex, translucence, aplasia, segmented hypertrophy and segmented aplasia and translucence. This result indicates that some of the glyphosate formulations have the capacity to cause widespread reproductive malformations in a way that could reduce the reproductive fitness of the amphibian. Care must therefore be taken to reduce the application rate of these formulations, particularly in aquatic environments.

scholarly journals Varied Clinical Presentations of Seven Patients With Mutations inCYP11A1Encoding the Cholesterol Side-Chain Cleavage Enzyme, P450scc

2013 ◽  
Vol 98 (2) ◽  
pp. 713-720 ◽  
Author(s):  
Meng Kian Tee ◽  
Michal Abramsohn ◽  
Neta Loewenthal ◽  
Mark Harris ◽  
Sudeep Siwach ◽  
...  
Keyword(s):  
Side Chain ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Clinical Presentations ◽  
Cleavage Enzyme

Imazapyr herbicideformulation induced multiple abnormalities in gonadal development of Xenopus laevis at environmentally relevant concentrations

2021 ◽  
Author(s):  
Oluwaseun Olusegun Babalola ◽  
Van Johannes Hannes
Keyword(s):  
Xenopus Laevis ◽  
Gonadal Development ◽  
Angular Deformity ◽  
Widespread Occurrence ◽  
Physiological Processes ◽  
Pristine Area ◽  
Abnormality Index ◽  
Reproductive Disruptions ◽  
Degree Of Association ◽  
Multiple Abnormalities

Abstract Mankind is now in the era of environmental contamination and pollution, where the environment has become a warehouse of its several toxicants. In fact, there are no longer any pristine area without these anthropogenic toxicants, with serious consequences on wildlife’s physiological processes including growth and reproduction. The widespread occurrence of pesticides for example, is being linked to numerous reproductive malformations in wildlife organisms, but the degree of association has not been characterised. Using the extended Xenopus Metamorphosis Assay (XEMA) protocol, the exposure impacts of imazapyr herbicide formulation (Arsenal), approved for aquatic environment was assessed on gonadal development of Xenopus laevis at environmentally relevant concentrations of 0.5, 2.0, and 3.5 mg/L. The formulation significantly reduced the mean body mass at premetamorphosis (NF-stage 55) at 3.5 mg/L concentration compared to the control. In sex ratio, the exposure only showed marginal fluctuations at all the exposure concentrations. For gonadal malformations, an abnormality index of 17.5%, 25%, and 35% was derived at 0.5 mg/L, 2.0, and 3.5 mg/L concentrations respectively, with malformations including tissues separation, segmented aplasia, aplasia, mixed sex, narrow hypoplasia, and angular deformity. This study showed that at relevant environmental concentrations, this formulation induced concentration dependent complex gonadal malformations, suggesting its potential capacities to induced serious reproductive disruptions that can negatively impacts fecundity, fertility, and general reproductive fitness of amphibians. In order to protect the wildlife from reproductive impacts, there is a serious need for cautions in application of this herbicide formulation

scholarly journals Loss of PI3K p110αin the Adipose Tissue Results in Infertility and Delayed Puberty Onset in Male Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Victoria L. Boughton Nelson ◽  
Ariel L. Negrón ◽  
Inefta Reid ◽  
Justin A. Thomas ◽  
Leon Yang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Negative Impact ◽  
Liver Steatosis ◽  
Delayed Puberty ◽  
Mrna Levels ◽  
Chain Cleavage ◽  
Testicular Weight ◽  
Cleavage Enzyme ◽  
Normal Body Weight ◽  
Puberty Onset

Deletion of PI3K catalytic subunit p110αin adipose tissue (aP2-Cre/p110αflx/flx,α−/− hereafter) results in increased adiposity, glucose intolerance, and liver steatosis. Because this endocrine organ releases hormones like leptin, which are important in reproductive physiology, we investigated the reproductive phenotype ofα−/− males. Compared to controls,α−/− males displayed delayed onset of puberty accompanied by a reduction in plasma LH levels and testicular weight. At postnatal day 30,α−/− mice exhibited normal body weight but elevated fasted plasma leptin levels. Testicular leptin gene expression was increased, whereas expression of the cholesterol transporter StAR and of P450 cholesterol side chain cleavage enzyme was decreased. Adultα−/− males were infertile and exhibited hyperandrogenemia with normal basal LH, FSH, and estradiol levels. However, neither sperm counts nor sperm motility was different between genotypes. The mRNA levels of leptin and of 17-beta-dehydrogenase 3, and enzyme important for testosterone production, were significantly higher in the testis of adultα−/− males. The mRNA levels of ERα, an important regulator of intratesticular steroidogenesis, were lower in the testis of adult and peripubertalα−/− males. We propose that chronic hyperleptinemia contributes to the negative impact that disrupting PI3K signaling in adipocytes has on puberty onset, steroidogenesis, and fertility in males.

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