Search PubMed⌕ Search

Biomedical subjects

C Benassayag

Publications and source records attributed to C Benassayag.

At least 55 records · Page 3Linked to original sources
PubMed1988

Selective changes in binding and immunological properties of human corticosteroid binding globulin by free fatty acids.

The steroid hormones, progesterone (P4) and cortisol (F), have different biological activities but are both bound to human corticosteroid binding globulin (CBG) with similar affinity. This study examines the effect of physiological concentrations of FFA on the binding of these steroids to purified CBG and to the serum of pregnant women. It also analyzes the influence of the FFA environment on the immunological behavior of CBG. Unsaturated fatty acids (UFA) had a dose-dependent inhibitory effect (P less than 0.001) on steroid binding to CBG which was offset by saturated fatty acid-induced potentiation of binding (P less than 0.01) when both were present with CBG. UFAs inhibited P4 binding more than F binding. Comparable results were obtained with pregnant serum or with pure CBG. UFAs seemed able, depending on their concentration, to promote different molecular states of CBG, some with enhanced F binding and significantly reduced P4 binding, and others in which both P4 and F binding was markedly reduced. Scatchard analysis of steroid binding to purified CBG indicated that the UFAs influenced the association constant (Ka) and the number of binding sites (n) for F and P4 binding differently. Low concentrations (less than 16 microM) of arachidonic acid (C20:4) slightly potentiated F binding, with no change in Ka and a 1.6-fold increase in n; this concentration of C20:4 reduced n for P4 binding by 40% and did not affect Ka. Higher C20:4 concentrations (greater than 32 microM), reduced the Ka for F binding but did not apparently change n; for P4 binding, Ka was sharply reduced and n increased. The apparent equilibrium dissociation constant (Kd) for both F and P4 binding varied nonlinearly and differently with increasing C20:4 concentration. Immunoelectrophoresis and immunoautoradiography showed a reduction, or loss, of CBG immunoreactivity in the presence of UFA. The extent of these changes varied with the concentration and class of the UFA. These results indicate that FFA induce conformational changes in CBG which may modulate its activity and so influence the role of this protein in both the endocrine and immune systems.

Arachidonic Acid↗
PubMed1987

Endotoxin-induced changes in sex steroid hormone levels in male rats.

Intravenous administration of Escherichia coli endotoxin (ENDO) was found to induce profound time and dose dependent changes in the serum steroid hormones, oestrone (E1), oestradiol (E2), corticosterone (B), progesterone (P4), 17 alpha-OH progesterone (17 alpha OHP4), and testosterone (T) of intact male rats. These changes were rapid, with a maximal response at 2 h and a return to close to normal values by 4 h. Non-lethal doses (0.01-2 mg/kg) of ENDO induced large increases in oestrogens (3-9-fold), P4 (4-fold) and B (2-3-fold) and decreased serum T (2-fold). The greatest increase in E2 level was seen with an ENDO dose of 2 mg/kg. Serum E1, E2 and T did not change in response to lethal ENDO doses (4-8 mg/kg); B, P4 and 17 alpha OHP4 levels alone were moderately elevated. Systemic mean arterial pressure was unchanged, except at the highest ENDO dose used. Thus, the hormonal responses are unlikely to be the result of hemodynamic changes. Low doses of ENDO did not produce an increase in serum E1 and E2 in adrenalectomized or orchidectomized rats. These results indicate that oestrogens are largely produced in the testis. The aromatization of the testicular and adrenal androgens can be stimulated by glucocorticoid.

Adrenal Glands↗
PubMed1987

Influence of indomethacin on the endotoxin-induced cardiodepressant effect of serum and steroid hormone changes in male rats.

Escherichia coli endotoxin has been shown to induce a cardiodepressant effect (CDE) and changes in steroid hormone concentrations in the serum of male rats, especially increases in estrogens and a decrease in testosterone. Pretreatment of rats with indomethacin (INDO) abolished these responses to endotoxin. Direct addition of INDO to primary cultures of rat heart cells blocked the cardiodepressant response of these cells to endotoxin-treated rat serum. These data, together with previous results, suggest that relationships between estrogens and CDE are possible, while these two parameters have different time courses and dose dependencies; in any case, the prostanoid system is likely involved since INDO is able to suppress both of them.

Animals↗
PubMed1986

Modifications of the properties of human sex steroid-binding protein by nonesterified fatty acids.

The effect of unsaturated and saturated nonesterified fatty acids (NEFAs) on the electrophoretic, immunological, and steroid-binding properties of human sex hormone-binding protein (SBP) were investigated. Tests were carried out on whole serum from pregnant women and on purified SBP using polyacrylamide gel electrophoresis, crossed immunoelectrophoresis with autoradiography, and equilibrium dialysis. All three methods showed that NEFAs influence the binding of sex steroids to SBP both in whole serum and with the purified protein. Saturated NEFAs caused a 1.5-2-fold increase in binding of dehydrotestosterone, testosterone, and estradiol to SBP, while unsaturated NEFAs, such as oleic (18:1) and docosahexaenoic (22:6) acids inhibited the binding of these steroids to SBP. Thus, unsaturated NEFAs in the concentration range 1-100 microM are more inhibitory for estradiol binding than for testosterone or dehydrotestosterone binding. In addition to these binding changes, polyacrylamide gel electrophoresis and immunoelectrophoretic studies revealed a shift in SBP from the slow-moving active native form to a fast-moving inactive one. There was also a reduction in the apparent SBP concentration by Laurell immunoelectrophoresis in the presence of unsaturated NEFA (5.5 nmol of NEFA/pmol of protein). These studies indicate that unsaturated NEFAs induce conformational changes in human SBP which are reflected in its electrophoretic, immunological, and steroid-binding properties. They suggest that the fatty acid content of the SBP environment may result in lower steroid hormone binding and thus increased free hormone levels.

Dihydrotestosterone↗
PubMed1986

Potentiation of estradiol binding to human tissue proteins by unsaturated nonesterified fatty acids.

Nonesterified fatty acids (NEFAs) have been recently shown in the rat to be involved in steroid hormone expression, having effects on plasma transport and intracellular activity. This study examines the influence of saturated and unsaturated NEFAs on estradiol (E2) binding to cytosol from human uterus, breast, and melanoma. Binding was analyzed after separation with dextran-coated charcoal or hydroxylapatite and by sucrose density gradient centrifugation. Unsaturated NEFAs induced a 2- to 10-fold increase (P less than 0.001) in E2 binding to cytosol from normal, fibromatous, and neoplastic uteri, while saturated NEFAs had a slight inhibitory effect (P less than 0.05). Similar effects were seen with cytosol from metastatic melanoma lymph nodes and neoplastic breast tissues. By contrast, unsaturated NEFAs did not increase E2 binding to serum from these patients. Density gradient centrifugation indicated that the increased binding was associated with the proteins present in the 2- to 4 S region. Analysis of E2 metabolites in the presence of unsaturated NEFAs showed the formation of water-soluble derivatives. Seventy percent of these E2 derivatives were trichloracetic acid precipitable, suggesting a covalent link between the steroid and a protein. The existence of such water-soluble metabolites could be erroneously interpreted as a true binding to soluble cytoplasmic receptors.

Breast↗
PubMed1984

Age-dependent responses of the serum non-esterified fatty acids to adrenalectomy and ovariectomy in developing rats.

We report detailed gas chromatography analyses of the non-esterified fatty acids in the sera of female rats during post-natal maturation. A marked age-dependent decrease of concentration is demonstrated for all classes of compounds. Total levels fall from about 0.8 mM at birth to about 0.25 mM, 60 days later. The decrease is most pronounced for the polyunsaturated acids, which represent 27 +/- 9% of total fatty acids at birth and 13 +/- 3% 60 days later. The effects of ovariectomy and adrenalectomy on the free fatty acid levels as a function of age are strikingly different before and after maturation. When ovariectomy is performed at 5, 9 and 15 days, the fatty acid levels respond by a significant (30-40%) decrease; when adrenalectomy is carried out at the same ages, a dramatic 3-5-fold increase of all classes of fatty acids is observed. By contrast, in older animals, both responses have virtually disappeared. Possible mechanisms underlying the age-dependent patterns and behaviour of the serum free fatty acids are briefly discussed.

Adrenalectomy↗
PubMed1984

Early released lipid-soluble cardiodepressant factor and elevated oestrogenic substances in human septic shock.

A cardiodepressant factor (CDF) able to decrease contractile activity of cultured rat heart cells was determined to be located in the lipid-soluble fraction of sera from men in septic shock. This heat-stable CDF has a molecular weight under 1000. Repeated fractionations of sera gave evidence of an oestrone-like chromatographic behaviour. Oestrone, oestradiol and cortisol were immunologically quantified in two groups (recovery and death) of men in septic shock. All of them were elevated in sera from patients with shock. Highest levels of oestrone 4330 pmol 1(-1), (SEM +/- 851, n = 15), oestradiol 1030 pmol 1(-1), (SEM +/- 220, n = 15) and cortisol 1096 pmol 1(-1), (SEM +/- 94, n = 15), were found in patients who failed to recover from shock. However, oestrone levels were the most striking, especially in the male. This study gives evidence for a polarity relationship between the CDF and oestrone, but natural oestrone does not appear to be a direct CDF. Moreover, this study shows that radioimmunoassay of oestrone could be an important index evaluating the severeness of septic shock.

Adult↗
PubMed1984

[Non-esterified fatty acids and alpha 1-fetoprotein are the modulators of uterine binding of estrogens during development in the rat].

We studied the effects of different classes of non-esterified fatty acids (NEFA) on the binding of natural and synthetic estrogens by uterine cytosolic receptors. The role of alpha 1-fetoprotein (AFP) in this process was also studied. Saturated fatty acids, irrespective of their concentration, slightly increased (120%) E2 binding to the 4S and 8S uterine cytosolic receptors. The effect of unsaturated fatty acids was dependent on their concentration: at 0.5 X 10(-4) M unsaturated NEFA potentiated the E2 binding to the receptor. At a higher concentration (2.0 X 10(-4) M), the NEFAs were highly inhibitory. This inhibition was dependent on the degree of unsaturation of the fatty acids. Tritiated arachidonic acid interacted directly with the 4S and 8S cytosol receptor. Furthermore, we demonstrated a double competition between murine AFP and the 8S receptor for estrogens and unsaturated NEFA. The effect of these hydrophobic ligand exchanges between transport proteins and receptors on the modulation of the action of estrogen is discussed.

Animals↗
PubMed1983

[Inhibition of the uterine binding of estrogens by unsaturated fatty acids in immature female rats].

We demonstrate that the interactions between the uterine cytosol proteins of 24 day old Rats and estradiol-17 beta (E2) are significantly influenced by physiological concentrations of non esterified fatty acids (2. 10(-4)M). We show that the specific binding of the hormone to the 8S uterine receptor, is markedly inhibited (50-80%) by the unsaturated fatty acids. The observed inhibition is a function both of acid dose and acid unsaturation degree. The polyunsaturated arachidonic and docosahexaenoic acids are the strongest inhibitors, whereas the saturated palmitic and stearic acids do not displace the E2 from the 8S receptor.

Animals↗
PubMed1983

The role of nonesterified fatty acids and of alpha 1-fetoprotein in estrogen-dependent endocrine systems.

We discuss the various experimental findings to date that indicate that AFP may be considered as a positive or negative modulator of estrogenic action. Moreover, we show that this protein, even when nonestrogenophilic, is able to bind other hydrophobic ligands, in particular nonesterified fatty acids. These fatty acids inhibit the binding of estrogens to murine AFP as well as to the cytosolic estrogen receptors. Thus, the AFPs of all species--whether or not estrogenophilic--might play an endocrinologic role through the intermediary of the unsaturated fatty acids to which they associate with high affinity.

Animals↗
PubMed1982

Developmental patterns of levels of corticosterone and of corticosterone binding in the serum of female rats: effects of ovariectomy and adrenalectomy.

Corticosterone concentrations and corticosterone binding in the serum were studied in immature female rats, using radioimmunoassay and batchwise gel equilibrium techniques. A parallel developmental pattern was found for corticosterone levels and its serum binding with a neonatal drop, followed by low levels until 12 days of age and a rise between 12 and 28 days of age. Effects of adrenalectomy, of ovariectomy, of the combined operation and of sham-operations, performed at various ages, were also studied. Adrenalectomy performed at 5 days of age did not decrease serum corticosterone concentrations within a 6-day period whereas it did in older rats. Complete disappearance of corticosterone from the blood occurred only in adult rats after combined adrenalectomy/ovariectomy. Ovariectomy and sham-operations in the younger age groups (5-15 days) caused a gradual increase in corticosterone concentration with maximal values 6 days after operation or later. The response of corticosterone secretion to these operations became more moderate and quicker, i.e. more adult-like, at 28 days of age, the age where corticosterone concentrations in intact rats also seemed to reach a plateau at an adult-like level. Corticosterone binding changed only marginally after ovariectomy or sham-operations until 28 days of age, when an increase was induced by these operations. After adrenalectomy or combined adrenalectomy/ovariectomy, however, marked increases in serum binding of corticosterone were always seen. In summary: though a parallel developmental pattern of serum corticosterone levels and corticosterone binding was seen in the maturing rat, interference with the normal condition causes divergent responses in these two parameters. Moreover, the responses vary with maturational age.

Adrenalectomy↗
PubMed1981

Mouse alpha 1-fetoprotein and albumin. A comparison of their binding properties with estrogen and fatty acid ligands.

The binding of estradiol-17 beta (E2), diethylstilbestrol (DES), and polyene fatty acids, in particular arachidonate (C20:4), to alpha 1-fetoprotein (alpha-FP) and albumin purified from mouse embryo sera was studied using equilibrium dialysis and electrophoretic techniques. E2, arachidonate, and DES all bind to alpha-FP, but with decreasing strength. E2 is a high affinity, low capacity ligand (Ka approximately 0.8 X 10(8) M-1 and approximately 0.3 sites/mol of alpha-FP at 25 degrees C); arachidonate is a weaker ligand disposing of more sites (Ka approximately 0.3 X 10(7) M-1 and 4-5 sites/mol of alpha-FP); the binding of DES is of comparatively low affinity and capacity (Ka approximately 0.2 X 10(7) M-1 and n approximately 0.7/mol of alpha-FP). In spite of different structures and equilibrium parameters, E2, DES, and arachidonate are able to compete with each other for binding to the fetoprotein. The C22:4 and C22:6 fatty acids are also efficient concentration-dependent inhibitors of E2 or DES binding. Albumin binds the fatty acids and DES, but equilibrium parameters are different from those of alpha-FP. In particular, arachidonate is a better ligand for albumin, where it interacts with at least two classes of apparent sites (Ka1 approximately 0.3 X 10(8) M-1 and n1 approximately 1; Ka2 approximately 0.2 X 10(7) M-1 and n2 approximately 30). In contrast to alpha-FP, albumin virtually does not bind E2. Also, no competition could be demonstrated between DES and fatty acid ligands for binding to albumin. None of the studied interactions, with either albumin or alpha-FP, was modified even by high doses of bilirubin. The possible functions of the various binding activities present in fetal sera in the process of growth are discussed.

Animals↗
PubMed1981

Evidence for an early lipid soluble cardiodepressant factor in rat serum after a sublethal dose of endotoxin.

The administration of a sublethal dose of E coli endotoxin (2 mg/kg) has been found to induce in the intact rat a slight decrease in mean carotid arterial pressure only 16 hours later. No death occurred whereas the same dose injected in the adrenalectomized rat caused lethality, and so did the higher dose (3 mg/kg) in the intact rat. Sera sampled two, four and 16 hours after administration of endotoxin (2 mg/kg) depressed contractile activity and the chronotropic response of isoproterenol in cultured rat heart cells. Such properties were not noted with sera sampled one or 24 hours after endotoxin administration. These cardiodepressant effects were localized in the lipid soluble fraction of endotoxin serum and absent in the fat-free portion. And yet neither endotoxin nor nonesterified fatty acid (NEFA) serum fraction was involved, since they did not alter cell culture activity. Moreover, though total or individual NEFA levels in endotoxic serum were higher than those of control rat serum four hours after endotoxin injection, they were not significantly different from control 16 hours later. It is concluded that the administration of a sublethal dose of endotoxin to the intact rat induces early and prolonged (up to 14-16 hours) release of one or more humoral lipid soluble cardiodepressant factor(s), even in the absence of systemic hypotension.

Adrenalectomy↗