THE EFFECT OF 2-BROMO-α-ERGOCRYPTINE (CB154) ADMINISTRATION ON THE HORMONE LEVELS, ORGAN WEIGHTS, PROSTATIC MORPHOLOGY AND ZINC CONCENTRATIONS IN THE MALE RAT

1976 ◽  
Vol 83 (1) ◽  
pp. 211-224 ◽  
Author(s):  
M. E. Harper ◽  
V. Danutra ◽  
J. A. Chandler ◽  
K. Griffiths
Keyword(s):  
Prostatic Tissue ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Prolactin ◽  
Cell Organelles ◽  
Adenyl Cyclase Activity ◽  
Zinc Concentrations ◽  
High Concentrations

ABSTRACT 2-Bromo-α-ergocryptine (CB154) administration to male rats produced a significant decrease in plasma prolactin levels without changing the LH and testosterone concentrations. The weights of the accessory sex tissues, testes, adrenals and kidney were unaltered by the treatment. Zinc concentration and distribution in the cell organelles of the prostatic tissue was markedly changed by CB154 treatment. No changes in the uptake of testosterone in vivo occurred in the treated animals. Prolactin did not consistently influence the prostatic adenyl cyclase activity in vitro and only at high concentrations was the testosterone uptake in vitro with cultures of prostatic tissue increased.

Quantification of the Uncertainties in Extrapolating From In Vitro Androgen Receptor Antagonism to In Vivo Hershberger Assay Endpoints and Adverse Reproductive Development in Male Rats

2020 ◽  
Vol 176 (2) ◽  
pp. 297-311
Author(s):  
Leon E Gray ◽  
Johnathan R Furr ◽  
Christy S Lambright ◽  
Nicola Evans ◽  
Phillip C Hartig ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Adverse Outcome ◽  
In Utero ◽  
Male Rats ◽  
Male Rat ◽  
Rat Offspring ◽  
Hershberger Assay ◽  
Key Events

Abstract Multiple molecular initiating events exist that disrupt male sexual differentiation in utero including androgen receptor (AR) antagonism and inhibition of synthesis, and metabolism of fetal testosterone. Disruption of androgen signaling by AR antagonists in utero reduces anogenital distance (AGD) and induces malformations in F1 male rat offspring. We are developing a quantitative network of adverse outcome pathways that includes multiple molecular initiating events and key events linking anti-AR activities to permanent reproductive abnormalities. Here, our objective was to determine how accurately the EC50s for AR antagonism in vitro or ED50s for reduced tissue growth in the Hershberger assay (HA) (key events in the adverse outcome pathway) predict the ED50s for reduced AGD in male rats exposed in utero to AR antagonists. This effort included in-house data and published studies from the last 60 years on AR antagonism in vitro and in vivo effects in the HA and on AGD after in utero exposure. In total, more than 250 studies were selected and included in the analysis with data from about 60 potentially antiandrogenic chemicals. The ability to predict ED50s for key events and adverse developmental effects from the in vitro EC50s displays considerable uncertainty with R2 values for HA and AGD of < 6%. In contrast, there is considerably less uncertainty in extrapolating from the ED50s in the HA to the ED50s for AGD (R2 value of about 85%). In summary, the current results suggest that the key events measured in the HA can be extrapolated with reasonable certainty to predict the ED50s for the adverse in utero effects of antiandrogenic chemicals on male rat offspring.

ATRIAL NATRIURETIC PEPTIDE IS A PHYSIOLOGICAL INHIBITOR OF ACTH RELEASE: EVIDENCE FROM IMMUNONEUTRALIZATION IN VIVO

1991 ◽  
Vol 131 (3) ◽  
pp. R9-R12 ◽  
Author(s):  
G. Fink ◽  
R.C. Dow ◽  
D. Casley ◽  
C.I. Johnston ◽  
A.T. Lim ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Concentrations ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Prolactin ◽  
Acth Secretion ◽  
Acth Release ◽  
Atrial Natriuretic

ABSTRACT The brain is thought to exert a predominantly stimulatory action on ACTH secretion mediated mainly by corticotrophin-releasing factor-41 (CRF-41) and arginine vasopressin (AVP). Several data, however, also point to the existence of an ACTH-inhibiting factor. Atrial natriuretic peptide (ANP), at concentrations found in hypophysial portal blood, inhibits ACTH release in vitro. The aim of the present studies was to use ANP immunoneutralization to determine whether ANP does in fact inhibit ACTH release in vivo. Intracerebroventricular infusion (I μl/min for 30 min) of sheep anti-ANP serum into male rats anaesthetized with sodium pentobarbitone had no significant effect on jugular venous plasma concentrations of ACTH or LH but did decrease significantly the plasma concentrations of prolactin. Intravenous infusion of 0.8 ml sheep anti-ANP serum but not control (non-immune) sheep serum, through an indwelling intra-atrial cannula in conscious male rats resulted in a marked and significant increase in plasma ACTH and corticosterone concentrations. The ACTH and corticosterone response to a 30-s ether stress was not significantly potentiated in the same conscious rats infused with anti-ANP serum. Intra-atrial infusion of anti-ANP did not significantly affect plasma prolactin, LH, glucose or sodium concentrations or plasma osmolality. These results show for the first time that ANP is a potent inhibitor of ACTH secretion in the conscious male rat and that, therefore, ANP is a hypothalamic neurohormone which is likely to play an important inhibitory role in the neural control of ACTH release.

PRODUCTION OF MALE PSEUDOHERMAPHRODITISM IN RATS BY TWO NEW INHIBITORS OF STEROID 17α-HYDROXYLASE AND C 17-20 LYASE

1976 ◽  
Vol 71 (3) ◽  
pp. 289-297 ◽  
Author(s):  
A. S. GOLDMAN ◽  
R. D. EAVEY ◽  
MARY K. BAKER
Keyword(s):  
Enzyme Inhibitors ◽  
Neonatal Rat ◽  
Male Rats ◽  
Male Rat ◽  
Pregnant Rats ◽  
Adult Rat ◽  
Rat Pups ◽  
Potent Inhibition

SUMMARY Two new synthetic steroid analogues, (I) 16β-bromo-3β,17α-dihydroxy-5α-pregnane-11,20-dione and (II) 17β-ureido-1,4-androstadien-3-one have been shown to give kinetic patterns consistent with active-site-directed irreversible inhibition of adult rat testicular microsomal steroid 17α-hydroxylase and C17-20 lyase in vitro. Administration of both analogues to adult male rats for 24 h produced potent inhibition of these testicular enzymes in vivo. Given to pregnant rats during the critical period of male organogenesis they produced hypospadias: a characteristic of the syndrome in man in which these enzymes are defective genetically. Given to male rat pups during the first 9 days of life, inhibitor II produced significantly smaller prostates and seminal vesicles in adulthood, indicating the usefulness of this inhibitor in studies on the role of testosterone in neonatal programming of target organ size in adulthood. Thus, two new enzyme inhibitors have been shown to block testosterone production in the foetal and neonatal rat selectively at the site of the hydroxylase without other apparent hormonal effects or influence on adrenal size.

Glucocorticoid–dependent maintenance of CYP2C11–dependent oxidation in male rat liver in vivo

2000 ◽  
Vol 19 (2) ◽  
pp. 126-131 ◽  
Author(s):  
M Murray
Keyword(s):  
Rat Liver ◽  
Male Rats ◽  
Male Rat ◽  
Hormonal Factors ◽  
Adrenal Hormones ◽  
Male Specific ◽  
Physiological Correlate ◽  
Made In

1 Hormonal factors participate in the regulation of xenobiotic metabolising enzymes in liver. Hepatic xenobiotic oxidation capacity is decreased in adrena-lectomised rats, which directly implicates adrenal hormones in the control of cytochrome P450 (CYP) expression. In addition, recent studies in cultured hepatocytes have demonstrated that low concentra-tions of glucocorticoid upregulate the male-specific CYP2C11, which is a major enzyme that catalyses xenobiotic and steroid hydroxylations in rat liver. The present study evaluated whether glucocorticoid or mineralocorticoid may be the adrenal factor that contributes to the in vivo expression of CYP2C11 in liver. 2 Adrenalectomy of male rats selectively decreased CYP2C11-dependent 2a-/16a-hydroxylation of testos-terone and other steroid substrates to 60-70% of control, whereas activities mediated by other constitu-tive CYPs were unaffected. The decrease in CYP2C11 activity was due to impaired protein expression in liver after adrenalectomy. Administration of dexametha-sone (DEX; 0.2 mg/kg i.p. daily for 6 days) restored CYP2C11 activity and protein, whereas the mineralo-corticoid deoxycorticosterone (DOC) and adrenocorti-cotropic hormone (ACTH) were ineffective. 3 These findings establish that glucocorticoids have a partial role in the maintenance of CYP2C11 expression and associated microsomal oxidation in liver and provide a physiological correlate for similar observa-tions made in vitro in hepatocyte culture.

FURTHER STUDIES ON THE UPTAKE OF ANDROGEN BY SOME ORGANS OF THE MALE RAT

1970 ◽  
Vol 63 (3) ◽  
pp. 489-498 ◽  
Author(s):  
Kjell J. Tveter
Keyword(s):  
Muscle Tissue ◽  
Specific Activity ◽  
Seminal Vesicles ◽  
Radioactive Material ◽  
Male Rats ◽  
Ventral Prostate ◽  
Supernatant Fraction ◽  
Male Rat

ABSTRACT [1,2-3H]Testosterone with a specific activity of 42.3 Ci/mmole was injected intramuscularly to adult castrated male rats. There was a selective uptake of radioactivity by the prostate, where a high and prolonged accumulation of radioactive material was found, in contrast to the much lower uptake by muscle tissue. The influence of castration on the uptake was investigated. In the ventral prostate, the uptake was 205% higher in animals castrated 24 h previously than in non-castrated animals. The corresponding values for the lateral prostate, the coagulating glands and the seminal vesicles were 120%, 165% and 213% respectively. The uptake by the dorsal prostate was only about 23% higher one day after orchidectomy. The uptake by muscle was apparently not influenced by castration. Following homogenization of the coagulating glands and the dorsal and ventral prostate, some of the radioactivity in the 105 000 × g supernatant fraction 1 h after the administration of [1,2-3H] testosterone in vivo was associated with macromolecules. In the lateral prostate an interaction between radioactive material and soluble macromolecules was only found in vitro.

The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S367-S375 ◽  
Author(s):  
Allen W. ROOT ◽  
Dorothy SHULMAN ◽  
Jennifer ROOT ◽  
Frank DIAMOND
Keyword(s):  
Growth Hormone ◽  
Thyroid Hormones ◽  
Secretory Response ◽  
Metabolic Effects ◽  
Male Rats ◽  
Male Rat ◽  
Peripheral Tissues ◽  
Releasing Hormone

ABSTRACT Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

Chemosensitizing Activity of Histone Deacetylases Inhibitory Cyclic Hydroxamic Acids for Combination Chemotherapy of Lymphatic Leukemia

2018 ◽  
Vol 18 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Denis V. Mishchenko ◽  
Margarita E. Neganova ◽  
Elena N. Klimanova ◽  
Tatyana E. Sashenkova ◽  
Sergey G. Klochkov ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Acute Toxicity ◽  
Histone Deacetylases ◽  
Hydroxamic Acids ◽  
Water Soluble ◽  
Male Rat ◽  
Hybrid Male ◽  
Cyclic Hydroxamic Acids

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis. Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents. Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study. Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg. Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.

scholarly journals Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets

2020 ◽  
Vol 318 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Richard A. Jacobson ◽  
Kiedo Wienholts ◽  
Ashley J. Williamson ◽  
Sara Gaines ◽  
Sanjiv Hyoju ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Healing Process ◽  
Abdominal Sepsis ◽  
Infectious Complications ◽  
Fibrinolytic System ◽  
Clinical Safety ◽  
High Concentrations ◽  
Clinically Significant

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

scholarly journals Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review

2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell
Keyword(s):  
Systematic Review ◽  
Tissue Engineering ◽  
Collagen Type I ◽  
The Body ◽  
Pool Data ◽  
Type I ◽  
High Concentrations ◽  
Increased Strength

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

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