FSH-induced aromatase activity in porcine granulosa cells: non-competitive inhibition by non-aromatizable androgens

1986 ◽  
Vol 108 (3) ◽  
pp. 335-341 ◽  
Author(s):  
W. K. Chan ◽  
C. H. Tan
Keyword(s):  
Induction Period ◽  
Granulosa Cells ◽  
Competitive Inhibition ◽  
Inhibitory Effect ◽  
Reciprocal Relationship ◽  
Test Period ◽  
Aromatase Activity ◽  
Porcine Granulosa Cells ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition

ABSTRACT The aim of this study was to examine the inhibitory effect of the non-aromatizable androgens on FSH-stimulated aromatase activity in porcine granulosa cells. The cells were isolated from medium-sized follicles (4–6 mm) of prepubertal pigs, and cultured under chemically defined conditions in the presence of FSH (1 μg/ml, NIADDK-oFSH-S13) with and without the androgens for an initial 48-h induction period. Subsequently, the spent medium was replaced with fresh medium containing only testosterone as substrate and the cells were reincubated for a further 6 h. The conversion of this steroid to oestradiol-17β during this latter 'test' period was taken as a measure of the aromatase activity. The addition of 5α-dihydrotestosterone (DHT) into cultures of FSH-stimulated cells during the induction period resulted in a definite dose-dependent inhibition (30–70%) of the aromatase activity expressed in the test period. This inhibitory action, of the mixed non-competitive type, is characterized by a decrease in the apparent Vmax and an increase in the Km value, suggestive of an androgen inhibition of FSH-stimulated aromatase synthesis. This inhibition was also shown by the other 5α- and 5β-reduced androgens: 5β-androstanedione was the most effective, while DHT was the least. Other steroids such as pregnenolone and progesterone were inhibitory, but testosterone and diethylstilboestrol were stimulatory. These results suggest an important mechanism for the intrafollicular control of oestrogen synthesis, involving a possible reciprocal relationship between aromatase and 5α-reductase activities. J. Endocr. (1986) 108, 335–341

Involvement of estrogens in the regulation of granulosa cell aromatase activity

1983 ◽  
Vol 61 (5) ◽  
pp. 507-511 ◽  
Author(s):  
S. A. J. Daniel ◽  
D. T. Armstrong
Keyword(s):  
Induction Period ◽  
Granulosa Cells ◽  
Follicle Stimulating Hormone ◽  
Test Period ◽  
Aromatase Activity ◽  
High Concentration ◽  
Synthetic Estrogen ◽  
Immature Rats ◽  
Estradiol 17Β ◽  
Positive Effect

Androgens have been shown to enhance follicle-stimulating hormone (FSH) induced aromatase activity in cultured granulosa cells obtained from the ovaries of immature rats, however, aromatizable androgens are more effective than nonaromatizable androgens. The present study was designed to investigate the possibility that aromatization of androgens to estrogens is responsible for the greater effectiveness of aromatizable androgens. Granulosa cells were cultured during a 36-h induction period in the presence of FSH, FSH + testosterone, or FSH + dihydrotestosterone with or without 4-acetoxy-4-androstene-3,17-dione (4-acetoxy-A), an inhibitor of aromatase activity. Treatment with androgens enhanced aromatase activity measured as accumulation of estradiol-17β during a 6-h test period with testosterone added as substrate. The effects of both androgens on FSH-induced aromatase activity were blocked by 4-acetoxy-A. Presence of a high concentration of diethylstilbestrol (DES), a synthetic estrogen, during the induction period had a significant positive effect on FSH-induced estradiol-17β accumulation during the test period. All lower doses were ineffective. Nafoxidine, an antiestrogen known to inhibit binding of estrogens to their intracellular receptors, had no effect on enhancement of FSH-induced aromatase by testosterone. The results of these experiments suggest that estrogens synthesized by granulosa cells in culture are only partially responsible for the greater ability of testosterone to enhance FSH-induced aromatase activity compared with that of dihydrotestosterone (DHT). Other factors such as differential rates of androgen metabolism and receptor affinities are probably the major determinants of androgen potency.

scholarly journals Potential Antidiabetic Effects of Extracts from Four Medicinal Plants Used in Burkina Faso by Inhibition of Alpha-Amylase

Diabetology ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 250-258
Author(s):  
Judith N. Semporé ◽  
Mamounata Diao ◽  
Lassina Ouattara ◽  
Paulin Ouoba ◽  
Windmi Kagambega ◽  
...  
Keyword(s):  
Plant Extracts ◽  
Competitive Inhibition ◽  
Inhibitory Effect ◽  
Rice Starch ◽  
Inhibitory Effects ◽  
Sclerocarya Birrea ◽  
Dependent Inhibition ◽  
Phytochemical Compounds ◽  
Dose Dependent Inhibition ◽  
Liquid Fractionation

Background: The purpose of this study was to evaluate α-amylase inhibitory effects of hydroethanolic extracts of bark from Daniella oliveri, Sclerocarya birrea, Maranthes polyandra, and Pteleopsis suberosa to fight type-II diabetes. Methods: Compound extractions were performed by hydroethanol maceration followed by liquid-liquid fractionation with solvents. TLC profiling was carried out with different fractions. The inhibitory effects of plant extracts on α-amylase activity were determined using rice starch as a substrate. Results: TLC profiling of different fractions showed different phytochemical compounds. The hydroethanolic plant extracts exhibited dose-dependent inhibition of α-amylase. D. oliveri displayed competitive inhibition, M. polyandra and S. birrea showed uncompetitive inhibition and Pteleopsis suberosa exerted mixed-inhibition. M. polyandra extract exerted the highest inhibitory effect (IC50 = 0.5 mg/mL). Conclusions: The barks of M. polyandra exhibit a remarkable α-amylase inhibitory effect which can be a novel source of antidiabetic molecules.

Human kidney 11β-hydroxysteroid dehydrogenase: regulation by adrenocorticotropin?

1996 ◽  
Vol 134 (3) ◽  
pp. 301-307 ◽  
Author(s):  
S Diederich ◽  
M Quinkler ◽  
K Miller ◽  
P Heilmann ◽  
M Schöneshöfer ◽  
...  
Keyword(s):  
Human Kidney ◽  
Kinetic Studies ◽  
Hydroxysteroid Dehydrogenase ◽  
Inhibitory Effect ◽  
Benjamin Franklin ◽  
Dependent Inhibition ◽  
Direct Inhibitory Effect ◽  
Dose Dependent Inhibition ◽  
Endogenous Substrates ◽  
Radioactive Detection

Diederich S, Quinkler M, Miller K, Heilmann P, Schöneshöfer M, Oelkers W. Human kidney 11βhydroxysteroid dehydrogenase: regulation by adrenocorticotropin? Eur J Endocrinol 1996;134:301–7. ISSN 0804–4643 In ectopic adrenocorticotropin (ACTH) syndrome (EAS) with higher ACTH levels than in pituitary Cushing's syndrome and during ACTH infusion, the ratio of cortisol to cortisone in plasma and urine is increased, suggesting inhibition of renal 11β-hydroxysteroid dehydrogenase (11β-HSD) by ACTH or by ACTH-dependent steroids. Measuring the conversion of cortisol to cortisone by human kidney slices under different conditions, we tested the possibility of 11β-HSD regulation by ACTH and corticosteroids. Slices prepared from unaffected parts of kidneys removed because of renal cell carcinoma were incubated with unlabeled or labeled cortisol, and cortisol and cortisone were quantitated after HPLC separation by UV or radioactive detection. The 11β-HSD activity was not influenced by incubation with increasing concentrations (10−12–10−9 mol/l) of ACTH (1–24 or 1–39) for 1 h. Among 12 ACTH-dependent steroids tested (10−9–10−6 mol/l), only corticosterone (IC50 = 2 × 10−7 mol/l), 18-OH-corticosterone and 11βOH-androstenedione showed a significant dose-dependent inhibition of 11β-HSD activity. The percentage conversion rate of cortisol to cortisone was concentration dependent over the whole range of cortisol concentrations tested (10−8–10−5 mol/l). A direct inhibitory effect of ACTH on 11β-HSD is, therefore, unlikely. The only steroids inhibiting the conversion of cortisol to cortisone are natural substrates for 11β-HSD Kinetic studies show a saturation of the enzyme at high cortisol concentrations. Thus, the reduced percentage renal cortisol inactivation in EAS seems to be due mainly to overload of the enzyme with endogenous substrates (cortisol, corticosterone and others) rather than to direct inhibition of 11β-HSD by ACTH or ACTHdependent steroids, not being substrates of 11β-HSD. S Diederich, Department of Endocrinology, Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany

Nickel inhibits endothelin-induced contractions of vascular smooth muscle

1990 ◽  
Vol 258 (6) ◽  
pp. C1025-C1030 ◽  
Author(s):  
K. Blackburn ◽  
R. F. Highsmith
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Porcine Coronary Artery ◽  
Force Development ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Endothelin (ET)-induced contractions of vascular smooth muscle (VSM) are dependent on extracellular Ca2+ yet display only partial sensitivity to L-type Ca2+ antagonists. The purpose of this study was to evaluate the effect of nickel (Ni2+), a Ca2+ channel antagonist with clearly documented differential potency toward L- vs. T-type Ca2+ currents on ET-mediated contractions in VSM. Treatment of rings of left anterior descending porcine coronary artery (LAD) with Ni2+ produced a profound dose-dependent inhibition of isometric force development in response to porcine ET (ET-1). At a concentration of 360 microM, Ni2+ exerted a significant inhibitory effect on contracture in response to doses of ET-1 ranging from 3 to 100 nM. In contrast, the same concentration of Ni2+ failed to significantly affect peak force development in response to KCl depolarization (5-77 mM) or to phenylephrine (0.3-30 mM). In addition, 360 microM Ni2+ significantly inhibited the contractile response of rat aorta to 10 nM ET-1. We conclude that ET-1 activates a Ni2(+)-sensitive process in VSM which may signal an additional Ca2+ influx pathway that appears to be functionally distinct from the L-type Ca2+ channel.

Sodium cromoglycate: evidence of tachykinin antagonist activity in the human skin

1993 ◽  
Vol 75 (1) ◽  
pp. 167-172 ◽  
Author(s):  
D. C. Crossman ◽  
M. R. Dashwood ◽  
G. W. Taylor ◽  
R. Wellings ◽  
R. W. Fuller
Keyword(s):  
Sodium Cromoglycate ◽  
Human Skin ◽  
High Performance ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Intradermal Injection ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

The mechanism of action of the antiasthmatic drug sodium cromoglycate (SCG) is unclear. One possibility is that SCG antagonizes the effects of the tachykinin substance P (SP), an agent known to cause airway edema. However, when SP is inhaled by humans, it has no demonstrable effect on airway function; therefore, the possibility that SCG prevents SP-induced changes in microvascular permeability was examined in human skin in vivo where potent edema-producing effects are seen. SCG (5–500 nmol) caused significant (P < 0.05) dose-dependent inhibition of SP-induced edema (wheal) formation when coadministered by intradermal injection. There was no effect on the nonreceptor-mediated flare response. SCG also significantly (P < 0.05) inhibited the wheal response to the related tachykinin neurokinin B but had no inhibitory effect on the cutaneous responses to histamine and prostaglandin E2. In addition, SCG (0.1–10 mM) caused dose-dependent inhibition of binding of SP labeled with 125I-labeled Bolton-Hunter to a number of tissues known to contain SP binding sites, as assessed by autoradiography. These concentrations were equivalent to the final concentrations of SCG found to inhibit the wheal response in the skin. The possibility that SCG interacted with SP was investigated both by gel filtration and high-performance liquid chromatography. No strong interaction was demonstrated with an 8,000 M excess of SCG under both hydrophobic and hydrophilic conditions. These results raise the possibility that SCG may have tachykinin antagonist properties.

Apolipoprotein AIV: a potent endogenous inhibitor of lipid oxidation

1998 ◽  
Vol 274 (5) ◽  
pp. H1836-H1840 ◽  
Author(s):  
Xiaofa Qin ◽  
Debi K. Swertfeger ◽  
Shuqin Zheng ◽  
David Y. Hui ◽  
Patrick Tso
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Lipoprotein Oxidation ◽  
Atherogenic Lipid Profile ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Endogenous Antioxidant ◽  
Knockout Animals

Overexpression of apolipoprotein (apo) AIV in transgenic mice confers significant protection against atherosclerosis in apoE knockout animals even in the presence of a more severe atherogenic lipid profile. Because lipoprotein oxidation has been recognized to be pivotal in development of atherosclerosis, the antioxidative activity of apoAIV was investigated. Fasting intestinal lymph was used to mimic conditions in the interstitial fluid, the potential site for lipoprotein oxidation in vivo. ApoAIV (10 μg/ml) significantly inhibited copper-mediated oxidation of lymph. This inhibitory effect was further evaluated using purified low-density lipoprotein. Addition of apoAIV (2.5 μg/ml) increased the time of 50% conjugated diene formation by 2.4-fold, whereas apoE or BSA did not show such a protection even at 20 μg/ml. Addition of apoAIV during the propagation phase also resulted in a dose-dependent inhibition. ApoAIV also protected macrophage-induced oxidation of fasting lymph. These results provide the first evidence that apoAIV is a potent endogenous antioxidant.

Inhibition of Tyrosinase by Protocatechuic Aldehyde

2004 ◽  
Vol 32 (01) ◽  
pp. 97-103 ◽  
Author(s):  
Jae Kyung No ◽  
Min Sun Kim ◽  
You Jung Kim ◽  
Song Ja Bae ◽  
Jae Sue Choi ◽  
...  
Keyword(s):  
Competitive Inhibition ◽  
Salvia Miltiorrhiza ◽  
Inhibitory Effect ◽  
Tyrosinase Activity ◽  
Medical Problems ◽  
Melanin Biosynthesis ◽  
Rate Limiting Step ◽  
Protocatechuic Aldehyde ◽  
Dependent Inhibition ◽  
Potent Inhibitory Effect

The purpose of this study was to determine the inhibitory action of protocatechuic aldehyde (PCA) on tyrosinase activity. PCA is one of the compounds found in the root of Salvia miltiorrhiza. Our study documented that PCA has a potent inhibitory effect on tyrosinase, which catalyzes the rate-limiting step of melanin biosynthesis. Although melanin biosynthesis has an essential function normally in human skin for defense against ultraviolet light of the sun, its abnormal activity as seen in pigmentation disorder could lead to serious medical problems. Our data showed that PCA, with concentrations ranging from 1×10-5 M to 8×10-5 M , exhibited dose-dependent inhibition of the enzyme activity with 50% of inhibition at 19.92×10-6 M . A further kinetic analysis on PCA inactivation of tyrosinase activity revealed a competitive inhibition of the enzyme at the L-tyrosine binding site. The findings of our present study merit further research on the applicability of PCA as a potential agent for treatment of pigmentation disorder.

scholarly journals Effects of transferrin on aromatase activity in porcine granulosa cells in vitro.

2009 ◽  
Vol 46 (4) ◽  
Author(s):  
Małgorzata Durlej ◽  
Małgorzata Duda ◽  
Katarzyna Knapczyk ◽  
Maria Słomczyńska
Keyword(s):  
Granulosa Cells ◽  
Aromatase Activity ◽  
Porcine Granulosa Cells

Porcine granulosa cell conditioned media as autocrine regulator of progesterone secretion

1993 ◽  
Vol 5 (1) ◽  
pp. 95
Author(s):  
RT Denkova ◽  
IG Ivanov ◽  
LN Kanchev
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cultured Cells ◽  
Primary Cultures ◽  
Inhibitory Effect ◽  
Conditioned Media ◽  
Progesterone Secretion ◽  
Porcine Granulosa Cells ◽  
Porcine Granulosa Cell

The ability of porcine granulosa cells to release a progesterone inhibiting substance(s) was examined in vitro. Granulosa cells (SGCs, MGCs and LGCs) were harvested from small, medium or large antral follicles respectively. The effect of granulosa cell conditioned media obtained from small follicles (SGCCM) was studied in the culture of LGCs by estimation of progesterone secretion; the conditioned media evoked the inhibition of progesterone secretion by the LGCs. SGCCM produced by various numbers of cultured granulosa cells showed a dose-related inhibition of progesterone production. A maximum inhibitory effect was noted when a 5-fold concentration of SGCCM was used. The addition of SGCCM had no effect on the growth of the cultured cells. The factor(s) inhibiting progesterone secretion appeared to be a nonsteroidal substance of molecular mass greater than 10 kDa and was heat-stable and trypsin-sensitive. The data presented support the suggestion that the conditioned media generated by primary cultures of SGCs contain nonsteroidal regulators capable of inhibiting progesterone secretion by cultured LGCs; this inhibitory activity can play an important autocrine regulatory role in the process of follicular differentiation.

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