Human Recombinant Activin-A Modulates the Steroidogenesis of Cultured Bovine Adrenocortical Cells

1992 ◽  
Vol 132 (3) ◽  
pp. R1-R4 ◽  
Author(s):  
Y. Nishi ◽  
M. Haji ◽  
S. Tanaka ◽  
T. Yanase ◽  
R. Takayanagi ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Activin A ◽  
Dependent Manner ◽  
Cortisol Secretion ◽  
Inhibitory Effects ◽  
Aldosterone Secretion ◽  
Adrenocortical Cells ◽  
Adrenal Steroidogenesis ◽  
Direct Inhibitory Effect ◽  
Dose Dependent

ABSTRACT The effect of human recombinant activin-A on adrenal steroidogenesis was studied in cultured bovine adrenocortical cells. Activin-A significantly reduced cortisol output from ACTH (10nmol/l)-stimulated adrenocortical cells incubated for 24 hours in a dose-dependent manner (10, 100 and 500ng activin-A /ml suppressed cortisol secretion by 19, 33 and 40%), although no significant effect was observed in the case of 3 h incubation. Dehydroepiandrosterone (DHEA) secretion from ACTH-stimulated adrenocortical cells incubated for 24 h was also decreased by the addition of activin-A in a dose-dependent manner. (10, 100 and 500ng activin-A /ml suppressed DHEA secretion by 22, 56 and 58%). These inhibitory effects of activin-A (100ng/ml) on cortisol and DHEA secretion were partially blocked by the addition of follistatin / FSH-Suppressing Protein (200ng/ml). In contrast, activin-A treatment resulted in no significant decrease in aldosterone secretion. There were no significant effects of activin-A on basal secretions of cortisol, DHEA or aldosterone from adrenocortical cells. These results suggest that activin-A has a direct inhibitory effect on ACTH-stimulated bovine adrenocortical steroidogenesis.

Self-inhibition of steroid secretion by amphibian adrenocortical cells is not mediated through glucocorticoid receptors

1991 ◽  
Vol 6 (3) ◽  
pp. 249-255 ◽  
Author(s):  
P. Netchitailo ◽  
A. Larcher ◽  
F. Leboulenger ◽  
M. Feuilloley ◽  
D. Philibert ◽  
...  
Keyword(s):  
High Performance ◽  
Glucocorticoid Receptors ◽  
Direct Action ◽  
Inhibitory Effect ◽  
Adrenocortical Cells ◽  
Reverse Phase ◽  
Steroid Secretion ◽  
Adrenal Steroid ◽  
Adrenal Steroidogenesis ◽  
Direct Inhibitory Effect

ABSTRACT To investigate a possible direct action of glucocorticoids on adrenal steroidogenesis, the effect of corticosterone on the conversion of pregnenolone into various metabolites by frog adrenal tissue was examined. Frog interrenal slices were incubated with [3H]pregnenolone (1 mCi/ml) and the various labelled metabolites analysed by reverse-phase high-performance liquid chromatography. With the methanol gradient used, five identified steroids were resolved: progesterone, 11-deoxycorticosterone, corticosterone, 18-hydroxycorticosterone and aldosterone. Corticosterone (10 μg/ml) induced a 45–80% decrease in all steroids synthesized from [3H]pregnenolone. In contrast, the glucocorticoid agonist dexamethasone did not reduce the rate of conversion of pregnenolone into its metabolites. In addition, the inhibitory effect of corticosterone was not reversed by the specific glucocorticoid antagonist RU 43044. These results show that corticosterone exerts a direct inhibitory effect on adrenal steroid secretion. In addition, our data indicate that the ultra-short regulation induced by corticosterone is not mediated through glucocorticoid receptors.

Interleukin-1 inhibits sodium and water transport in rabbit cortical collecting duct

1994 ◽  
Vol 266 (4) ◽  
pp. F674-F680 ◽  
Author(s):  
Y. Sakairi ◽  
Y. Ando ◽  
K. Tabei ◽  
E. Kusano ◽  
Y. Asano
Keyword(s):  
Water Transport ◽  
Collecting Duct ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cortical Collecting Duct ◽  
Direct Inhibitory Effect ◽  
Transepithelial Voltage ◽  
Dose Dependent

Interleukin-1 (IL-1) induces natriuresis and diuresis. In the present study, the effect of basolateral IL-1 on sodium and water transport was examined in the cortical collecting duct (CCD) perfused in vitro. IL-1, 10 pg/ml and 10 ng/ml, inhibited lumen-to-bath sodium flux (JNa, peq.min-1.mm tubule-1), depolarizing transepithelial voltage (Vt) in a time- and dose-dependent manner. The inhibitory effect of 10 ng/ml but not 10 pg/ml IL-1 on Vt and JNa was mitigated by 5 microM indomethacin (IND) in bath. Also, 10 ng/ml IL-1, which did not affect the basal hydraulic conductivity (Lp, x10(-7) cm.atm-1.s-1) by itself, inhibited the hydrosmotic effect of 20 pM basolateral arginine vasopressin, and 5 microM IND abolished this inhibitory effect of 10 ng/ml IL-1. The present study demonstrated direct inhibitory effect of basolateral IL-1 on sodium and water reabsorption in the rabbit CCD. The effect of IL-1 is suggested to be mediated, in part, by a cyclooxygenase metabolite(s).

Inhibitory effects of gossypol on adrenal function

1991 ◽  
Vol 124 (6) ◽  
pp. 672-678 ◽  
Author(s):  
Yan-Wan Wu ◽  
Constance L. Chik ◽  
Barry D. Albertson ◽  
W. Marston Linehan ◽  
Richard A. Knazek
Keyword(s):  
Adrenal Function ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Acth Stimulation ◽  
Adrenal Steroidogenesis ◽  
Cortisol Responses ◽  
Corticosterone Response ◽  
High Doses ◽  
Dose Dependent

Abstract. Gossypol, an antifertility agent, has inhibitory actions on many membrane-associated enzymes, suggesting that this agent might have a generalized effect on cell membranes. This hypothesis was examined in the present study using membranes and dispersed cells prepared from human and rat adrenal glands. Four parameters were determined: microviscosity as measured by fluorescence polarization of human adrenal microsomal- and mitochondrial-enriched membranes, adrenal steroidogenic enzymes; and cAMP and cortisol responses to ACTH. It was found that gossypol increased the polarization constants of microsomes and mitochondria in a dose-dependent manner. Of the three adrenal enzymes tested, both 3β-hydroxysteroid dehydrogenase Δ5-Δ4 isomerase and 11-hydroxylase were inhibited by gossypol, but not 21-hydroxylase. Using intact human adrenocortical cells, high doses of gossypol also inhibited the ACTH-stimulated cAMP and cortisol levels. The in vivo corticosterone response to ACTH in rats subjected to chronic gossypol treatment was also found to be reduced. These findings suggest that gossypol has multiple effects on adrenal function. Its effects on membrane microviscosity, adrenal steroidogenesis, cAMP and corticosterone responses to ACTH stimulation probably occur through a generalized membrane effect.

scholarly journals Effect of activin on production and secretion of prolactin and growth hormone in cultured rat GH3 cells

2000 ◽  
pp. 506-511 ◽  
Author(s):  
N Tamura ◽  
M Irahara ◽  
A Kuwahara ◽  
K Ushigoe ◽  
H Sugino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Activin A ◽  
Gh3 Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Gh Secretion ◽  
Gh Gene ◽  
Dose Dependent ◽  
Cells Cultured

OBJECTIVE: To evaluate the effect of the growth factor activin A on the secretion of prolactin (PRL) and GH in cultured GH3 cells. METHODS: The concentrations of PRL and GH secreted from GH3 cells cultured in media with and without activin A were measured by RIA, and the expression of PRL mRNA and GH mRNA were analyzed using the Northern blot method. RESULTS: Activin A significantly inhibited PRL release from GH3 cells cultured for 48h in a dose-dependent manner (activin: 0.3-3nM). The inhibitory effects of 3nM activin A were observed in the culture from 12h to 48h (53.2% of control). Activin A (3nM) also significantly inhibited the expression of PRL mRNA at 24h (33.8% of control). In contrast, activin A significantly stimulated GH release from GH3 cells cultured for 48h in a dose-dependent manner (activin: 0.3-3nM). The stimulatory effect of 3nM activin A was observed in the culture for 48h (157.6% of control). Activin A (3nM) also significantly stimulated the expression of GH mRNA at 24h (183.6% of control). In spite of these significant changes in PRL and GH secretion, pit-1 mRNA levels were not significantly changed by activin A. CONCLUSIONS: These findings indicated that activin A modulates PRL and GH secretion through the regulation of PRL and GH gene transcription in GH3 cells, but that these effects are unrelated to pit-1 gene expression.

Surfactant-associated protein inhibits phospholipid secretion from type II cells

1987 ◽  
Vol 63 (2) ◽  
pp. 692-698 ◽  
Author(s):  
W. R. Rice ◽  
G. F. Ross ◽  
F. M. Singleton ◽  
S. Dingle ◽  
J. A. Whitsett
Keyword(s):  
Pulmonary Surfactant ◽  
Lung Surfactant ◽  
Inhibitory Effect ◽  
Heat Denaturation ◽  
Type Ii Cells ◽  
Dependent Manner ◽  
Type Ii ◽  
Inhibitory Effects ◽  
Dose Dependent

Secretion of [3H]phosphatidylcholine ([3H]PC) from isolated rat pulmonary type II epithelial cells was inhibited by the surfactant-associated protein of Mr = 35,000 (SAP-35) purified from canine lung surfactant. SAP-35 inhibited [3H]PC secretion in a dose-dependent manner and significantly inhibited basal, phorbol ester, beta-adrenergic, and P2-purinergic agonist-induced [3H]PC secretion. SAP-35 significantly inhibited [3H]PC secretion from 1 to 3 h after treatment. The IC50 for inhibition of [3H]PC secretion by canine SAP-35 was 1–5 X 10(-6) g/ml and was similar for inhibition of both basal and secretagogue-stimulated release. Heat denaturation of SAP-35, addition of monoclonal anti-SAP-35 antibody, reduction and alkylation of SAP-35, or association of SAP-35 with phospholipid vesicles reversed the inhibitory effect on secretagogue-induced secretion. Inhibitory effects of SAP-35 were observed 3 h after cells were washed with buffer that did not contain SAP-35. Although SAP-35 enhanced reassociation of surfactant phospholipid with isolated type II cells, its inhibitory effect on secretion of [3H]PC did not result from stimulation of reuptake of secreted [3H]PC by type II cells. The inhibition of phospholipid secretion by SAP-35 was also not due to inhibition of PC or disaturated PC synthesis by SAP-35. SAP-35, the major phospholipid-associated protein in pulmonary surfactant, is a potent inhibitor of surfactant secretion from type II cells in vitro and may play an important role in homeostasis of surfactant in the alveolar space.

scholarly journals Inhibitory Effects of Bryophyllum pinnatum Leaf Extract on Inflammatory Biomarkers

2021 ◽  
pp. 7-13
Author(s):  
Adebayo Afees Oladejo ◽  
Onwubuya Emmanuel Ikechuckwu ◽  
Ogbunugafor Henrietta Aritetsoma ◽  
Okafor Chike Samuel ◽  
Ogbodo Chibuzor Uche
Keyword(s):  
Leaf Extract ◽  
Inhibitory Effect ◽  
Inflammatory Biomarkers ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Dose Dependent ◽  
Rich Content ◽  
Traditional Medical Practice ◽  
India And China ◽  
Bryophyllum Pinnatum

Bryophyllum pinnatum Lam. (Crassulaceae) called ‘Oda-opue’ in Igbo and ‘Abamoda’ in Yoruba are widely used as food and as medicines in traditional medical practice. They are found widely in tropical Africa, America, India and China. This study investigated the inhibitory effect of the hydro-ethanol leaf extract on inflammatory biomarkers. The Cotton Pellet Induced Granuloma method was used in the study. The plant extract significantly inhibited the inflammatory biomarkers, cyclooxygenases 1 and 2, interleukins 1β and 6, and prostaglandin E2, in a dose dependent manner indicating a reduction of inflammation in the rats. The study showed that B. pinnatum leaf extract possess a rich content of bioactive compounds which could be synthesized to produce new plant-based product to fight inflammatory disorders with fewer side effects.

scholarly journals EVALUATION OF THE CYTOCHROME P450 INHIBITORY EFFECT OF THYME OLEORESIN FROM THYMUS VULGARIS L. - AN IN VITRO STUDY

2018 ◽  
Vol 11 (9) ◽  
pp. 149
Author(s):  
Adeline Persia R ◽  
Anitha Roy ◽  
Lakshmi T
Keyword(s):  
Cytochrome P450 ◽  
Potassium Phosphate ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Thymus Vulgaris ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Ic50 Value ◽  
Dose Dependent

Objective: The objective of this study was to evaluate the effect of thyme oleoresin on cytochrome P450 (CYP3A4) enzyme.Materials and Methods: The different concentrations of thyme (5–100 μg/ml) were examined for its inhibitory property toward cytochrome P450 isoform (CYP3A4). Thyme, potassium phosphate buffer, CYP450 reagent, and substrate 7-Benzyloxy-4-trifluoromethylcoumarin were added to a 96-well plate. The mixtures were preincubated for 20 min at room temperature. The fluorescent intensities of the products were measured by PerkinElmer Enspire fluorescence reader using an excitation and emission wavelength of 405 nm and 460 nm, respectively. Values are expressed as mean ± standard error mean (n=3). IC50 was calculated by plotting concentrations of thyme against the corresponding percent inhibition.Results: All the tested concentrations of thyme showed inhibitory effect against CYP3A4 in a dose-dependent manner. At 5 μg/ml, it showed a percentage inhibition of 1.82±0.61, whereas 100 μg/ml showed 66.05±0.16. The IC50 value of thyme for CYP3A4 inhibitory activity was found to be 39.14 μg/ml.Conclusion: This study proves that the inhibitory effect of thyme oleoresin on cytochrome P450. The inhibitory effects of thyme indicate the possibilities of herb-drug interaction if this extract is coadministered with prescribed drugs that are metabolized by CYP3A4.

The inhibitory effects of some adenosine analogues on transmitter release at the mammalian neuromuscular junction

1986 ◽  
Vol 64 (11) ◽  
pp. 1446-1450 ◽  
Author(s):  
Yadhu N. Singh ◽  
William F. Dryden ◽  
Hsinyo Chen
Keyword(s):  
Transmitter Release ◽  
Rank Order ◽  
Electrophysiological Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Adenosine Analogues ◽  
Agonist Action ◽  
Dose Dependent

An electrophysiological study was made of the effects of four adenosine analogues, 2-chloroadenosine (2-CIA), 5′-N-ethylcarboxamidoadenosine (NECA), L-N6-phenylisopropyladenosine (L-PIA), and 2-(p-methoxyphenyl)-adenosine (CV-1674) on neurotransmitter release in the mouse phrenic nerve–hemidiaphragm preparation. All four drugs decreased miniature end-plate potential frequency in a dose-dependent manner. Evoked transmitter release in the cut diaphragm preparation was depressed by 2-CIA and CV-1674 to a similar extent. The ability of theophylline to antagonize the inhibitory effect of CV-1674 on spontaneous transmitter release was also established. On the basis of these results, the rank order of potencies was: L-PIA>NECA>2-CIA>CV-1674. A clear classification of receptor type could not be made, since the ratio of potencies of L-PIA and NEC A was narrow. Different slopes of the concentration–effect curves for 2-CIA and CV-1674 compared with L-PIA and NEC A suggest an additional component to simple agonist action in their overall effects.

Synthesis and Assessment of Novel Anti-chlamydial Benzylidene Acylhydrazides Derivatives

2018 ◽  
Vol 15 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Xiaofeng Bao ◽  
Ying Xue ◽  
Chao Xia ◽  
Yin Lu ◽  
Ningjing Yang ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dependent Manner ◽  
Iron Starvation ◽  
Hydrochloride Salt ◽  
Obligate Intracellular ◽  
Biphasic Life Cycle ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Dose Dependent ◽  
Better Than

Background: Chlamydiae, characterized by a unique biphasic life cycle, are a group of Gram-negative obligate intracellular bacterial pathogens responsible for diseases in a range of hosts including humans. Benzylidene acylhydrazide CF0001 could inhibit chlamydiae independent of iron starvation and T3SS inhibition. This finding promoted us to design and synthesize more benzylidene acylhydrazides to find novel anti-chlamydial agents. Methods: The carboxylic acids 1a-1d were coupled with Boc-hydrazide inpresence of EDCI and DMAP to obtain the intermediate 2a-2d in 60-62% yields. N-Boc deprotections were performed to obtain hydrazide hydrochloride salt 3a-3d. Nextly, the hydrazides were subjected to condensation with aldehydes to obtain benzylidene acylhydrazides 4a-4g in 30-52% yields in two steps. Results: Compound 4d exhibited best inhibitory effect on the formation and growth of chlamydial inclusions. The IC50 value of compound 4d for infectious progenies was 3.55 µM, better than 7.30 µM of CF0001. Conclusion: To find novel anti-chlamydial agents, we have designed and synthesized benzylidene acylhydrazides 4a-4g. Compounds 4a, 4d, 4g showed inhibitory activity on C. muridarum with the IC50 values from 3.55-12 µM. The 3,5-dibromo-4-hydroxyl substitutes on ring B are critical to keep their anti-chlamydial activity. Compound 4d inhibited C. muridarum in a dose-dependent manner without apparent cytotoxicity.

scholarly journals In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Zhang ◽  
Zengqiang Qu ◽  
Yanqing Zhou ◽  
Jin Zhou ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Drug Drug Interaction ◽  
Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

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