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F Homo-Delarche

Publications and source records attributed to F Homo-Delarche.

At least 73 records · Page 4Linked to original sources
PubMed1986

Presence of glucocorticoid receptors in cultured thymic epithelial cells.

We investigated the presence of glucocorticoid receptors (GC) in human thymic epithelial cells grown in primary cultures and in a pure epithelial rat cell line. These GR levels were compared to those determined concomitantly in fresh human thymocytes. The average number of sites were 54,457/cell for males (n = 8) and 58,224/cell for females (n = 8) with mean Kd values of 1.5 and 1.7 X 10(-8) M, respectively, in cultured human epithelial cells. These results are comparable to those obtained for rat thymic epithelial cells. Competition experiments showed that the relative affinities of the steroids tested were in decreasing order: dexamethasone greater than progesterone greater than testosterone and estradiol. This observation is compatible with binding to physiological GR. Moreover, the mean GR value appeared to be approximately 10 times higher for human thymic epithelial cells than for thymocytes. Thus, human epithelial cells as well as thymocytes should be considered as a specific target for glucocorticoid hormones.

Adult↗
PubMed1986

Involvement of prostaglandins in the response of frog adrenocortical cells to muscarinic receptor activation.

The role of prostaglandins (PGs) in the mechanism of action of acetylcholine (ACh) on frog adrenocortical cells has been examined. Administration of a single dose of ACh (5 X 10(-5) M) to perifused frog interrenal fragments, for 20 min, stimulated the production of corticosterone, aldosterone, PGE2 and 6-keto-PGF1 alpha. In contrast ACh did not significantly alter TXB2 production. The effect of ACh could be mimicked by muscarine (10(-5) M). Conversely, nicotine (10(-6) to 10(-4) M) was totally inactive. The increase in PG biosynthesis preceded the peak of corticosteroid release. Repeated 20-min pulses of ACh (5 X 10(-5) M) or muscarine (10(-5) M) given at 130-min intervals induced a desensitization phenomenon. In presence of indomethacin (5 X 10(-6) M), the effect of ACh on PG and steroid secretion was totally abolished. In calcium-free medium, the effect of ACh on PG and corticosteroid production was completely blocked. These results indicate that, in the frog, ACh stimulates corticosteroid secretion through a PG-dependent mechanism.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Pharmacological modulation of prostaglandin production by phagocytic cells of the thymic reticulum in relation to immunoregulation.

We cultured phagocytic cells derived from the thymic reticulum in order to study the regulation of prostaglandin (PG) production by antiinflammatory or immunostimulating agents. The kinetics of PGE2, 6-keto-PGF1 alpha and PGF2 alpha production were measured by specific radioimmunoassays of the supernatants harvested from cells treated with dexamethasone, a steroidal antiinflammatory drug and by two non steroidal inhibitors (indomethacin and sulindac) or by various immunostimulating agents, one of them, RU 41740 is currently being used in humans. Our results revealed that each of these drugs exerts a differential effect on the PG production, with a striking action on PGE2 synthesis, a lesser effect on 6-keto-PGF1 alpha production and almost no effect on PGF2 alpha synthesis. The possible mechanisms responsible for this complex regulation of PG production are discussed.

Adjuvants, Immunologic↗
PubMed1986

Role of prostaglandins in calcium-induced corticosteroid secretion by isolated frog interrenal gland.

The role of prostaglandins (PGs) in calcium-induced corticosteroid secretion by frog adrenal (interrenal) gland has been examined in vitro using a perifusion technique. Increasing concentrations of CaCl2 (4-10 mM) stimulated in a dose-dependent manner aldosterone, PGE2 and 6-keto-PGF1 alpha production, whereas TXB2 was not affected. The kinetics of the adrenal response to CaCl2 indicated that the increase in PG output always preceded that of steroid. Administration of cobalt (4 mM), a calcium-channel inhibitor, blocked the calcium-induced stimulation of PGs and corticosteroids. Infusion of indomethacin (5 X 10(-6) M), a specific cyclooxygenase inhibitor, significantly decreased the basal production of PGs and steroids, and prevented the stimulatory effect of CaCl2 (6 mM). Infusion of the calcium ionophore A 23187 (10(-6) M), for 20 min, induced a marked stimulation of PG and steroid production. Taken together, these data support the notion that biosynthesis of prostaglandins is associated with calcium-induced corticosteroid secretion in frog adrenal cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Role of prostacyclin on steroidogenesis by frog interrenal gland in vitro.

The role of prostacyclin (PGI2) on amphibian adrenal steroidogenesis was studied in vitro in perifused interrenal fragments from adult male frogs. Exogenous PGI2 (3 X 10(-8) M to 3 X 10(-5) M) and, in a lesser extent, 6-keto-PGF1 alpha increased both corticosterone and aldosterone production in a dose-related manner. Short pulses (20 min) of 0.88 microM PGI2 administered at 90 min intervals within the same experiment did not induce any desensitization phenomenon. A prolonged administration (6 h) of PGI2 gave rise to an important increase in steroid production followed by a decline of corticosteroidogenesis. Indomethacin (IDM, 5 microM) induced a marked reduction of the spontaneous secretion of corticosteroid which confirmed the involvement of endogenous PGs in the process of corticosteroid biosynthesis. The IDM-induced blockade of corticosterone and aldosterone secretion was totally reversed by administration of exogenous PGI2 in our model. Angiotensin II (AII) induced a massive release of 6-keto-PGF1 alpha, the stable metabolite of PGI2. The increase of 6-keto-PGF1 alpha preceded the stimulation of corticosterone and aldosterone secretions. In contrast, the administration of ACTH did not modify the release of 6-keto-PGF1 alpha. These results indicate that PGI2 might be an important mediator of adrenal steroidogenesis in frog. They confirm that the corticosteroidogenic actions of ACTH and AII are mediated by different mechanisms.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Regulation of prostaglandin E2 and plasminogen activator by various immunomodulators in human monocytes.

Mononuclear phagocyte populations and monocytes are able to produce, among numerous substances, a neutral protease, i.e. plasminogen activator (PA) and prostaglandins. Since it has been shown that prostaglandins (PGs) and particularly PGE2 could exert an inhibitory effect on PA production by macrophages, we have measured the in vitro production of PA and PGE2 by monocytes isolated from healthy donors. These monocytes were cultured either in the absence or the presence of various immunomodulators: lipopolysaccharide from E. coli, concanavalin A and RU 41740 or Biostim a broad spectrum immunostimulating agent isolated from Klebsiella pneumoniae (Cassenne Laboratories, France). The production of PGE2 was proportional to the number of monocytes per incubation, and at a given cell concentration varied greatly from one subject to another. When considering PGE2 productions, the type of the response to the different immunomodulators varied from subject to subject and ranged from stimulation to no effect, or even inhibition. Moreover, a statistically significant, inverse relationship exists between the spontaneous production of PGE2 and the effect of each immunomodulator. For a given subject, all agents always acted in the same way and there was an inverse relationship between the effects of the immunomodulators on plasminogen activator and PGE2 production.

Adjuvants, Immunologic↗
PubMed1986

Effect of serum on the metabolism of exogenous arachidonic acid by phagocytic cells of the mouse thymic reticulum.

Phagocytic cells derived from the mouse thymic reticulum (P-TR) were used to study the effect of serum on the metabolism of arachidonic acid (AA). After labeling with (14C)-AA in the presence of 10% serum, we failed to detect in the culture medium the presence of significant amounts of radiolabeled prostaglandins. In contrast, when the labeling period was carried out in serum-free medium, we observed the secretion of both cyclooxygenase and lipoxygenase derivatives. In addition, the pattern of arachidonate incorporation into cell lipids was different in the two culture conditions. In the presence of serum, the great majority of the radioactivity was found associated with phospholipids, whereas in serum-free medium, almost 50% of the incorporated fatty acid was associated with triglycerides. Since serum albumin is known to play a major role in the control of fatty acid uptake, we have studied the effect of the addition of 2% BSA to cells prelabeled in the absence of serum. This treatment switches the patterns of metabolite release and lipid labeling towards those of serum-treated cells. In addition, we showed that the effects of glucocorticoids on AA release differ markedly according to the composition of the culture medium.

Animals↗
PubMed1985

Opposite effects of a glucocorticoid and an immunostimulating agent on prostaglandin production by two different cell types.

Studies were performed to investigate the effects of several agents known to modulate wound healing on prostaglandin production by mouse embryo fibroblasts and adult thymic phagocytic cells in culture. Dexamethasone (10(-6)M) induced in both cell types a significant inhibition of the production of PGE2 and 6 keto PGF1 alpha, and a moderate inhibition of PGF2 alpha. Using an antiglucocorticoid compound, RU 38486, we were able to demonstrate that the inhibition of PG secretion represents a classical receptor-mediated effect of the steroid. In contrast, LPS and RU 41740 (5 micrograms/ml) induced a significant stimulation of PGE2 and 6-keto-PGF1 alpha secretion in the two types of cells. These results suggest that agents which modulate in different ways the process of tissue repair have opposite effects on PG production by cells involved in inflammatory and/or immunological reactions.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Prostaglandin production by phagocytic cells of the mouse thymic reticulum in culture and its modulation by indomethacin and corticosteroids.

The production of prostaglandins by phagocytic cells of the thymic reticulum in culture (P-TR) was studied by using high pressure liquid chromatography and radioimmunoassay. Radioimmunologic determinations showed that thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1 alpha (6 keto-PGF1 alpha) were the major compounds released into the culture medium, whereas prostaglandin F2 alpha (PGF2 alpha) was only a minor component. Indomethacin and dexamethasone exerted a similar pattern of differential inhibition of the secretion of prostanoids. PGE2 and 6-keto PGF1 alpha productions were markedly decreased by these anti-inflammatory drugs, whereas those of TXB2 and PGF2 alpha were not or were only slightly affected. Experiments performed with an antiglucocorticoid compound (RU 38486) showed that the steroid-induced inhibition of prostanoid secretion is a classical receptor-mediated action. These results demonstrated that phagocytic cells of the thymic reticulum, which resemble the thymic interdigitating cells, produce several types of prostaglandins. Because it has been described that P-TR regulate thymocyte proliferation in vitro via the secretion of both interleukin 1 and PGE2, these results suggest that anti-inflammatory agents may be able to modulate the thymic microenvironment and, consequently, thymocyte proliferation.

Animals↗
PubMed1984

Effect of antiglucocorticoids on dexamethasone-induced inhibition of uridine incorporation and cell lysis in isolated mouse thymocytes.

We have compared in isolated mouse thymocytes the action of progesterone, cortexolone, DXH (a 17-beta carboxamide derivative of dexamethasone) and RU 38486 (a new antiglucocorticoid molecule), on dexamethasone-induced inhibition of uridine incorporation and cell lysis, with the affinities of these drugs for glucocorticoid receptors. Our results show that progesterone, cortexolone and DXH which possess similar affinities for glucocorticoid receptors may exhibit variable, weak agonist and antagonist activities according to the parameter studied. RU 38486 was a potent competitor of dexamethasone and was able, when present in a 10-fold excess, to counteract almost completely the inhibitory action as well as the lytic action of 5 X 10(-8) M dexamethasone. This compound which exerts almost no agonist activity may therefore represent a useful tool to investigate the mode of action of antiglucocorticoids.

17-Hydroxycorticosteroids↗
PubMed1984

Role of adrenal hormones and prostaglandins in the control of mouse thymocytes lysis.

The cytolytic actions of glucocorticoids and of agents increasing cyclic AMP were studied in vitro in thymocyte suspensions isolated from adrenalectomized or hydrocortisone-treated mice. Although considered as corticoresistant cells, the thymocytes isolated from hydrocortisone-treated mice were lysed to the same extent although more slowly in vitro by dexamethasone than whole thymocyte populations (i.e. corticosensitive cells). Moreover, these two cell populations were shown to contain comparable amounts of glucocorticoid receptors and to be almost equally sensitive to the metabolic effects of glucocorticoids when measured by inhibition of RNA and DNA synthesis. Studies performed with corticosensitive cells showed that prostaglandin E2, isoproterenol and dibutyrilcyclic AMP were also able to induce cell lysis and that, isoproterenol and dexamethasone exerted additive cytolytic action in vitro. In vivo experiments showed also an additive effect of steroids and isoproterenol on thymus atrophy. In contrast, cells isolated from hydrocortisone-treated animals were not sensitive to the cytotoxic action of prostaglandin E2, isoproterenol and dibutyril cyclic AMP. This difference between the two populations was not associated with any difference in the responsiveness of adenylate cyclase as determined following isoproterenol-induced accumulation of cyclic AMP. The cytolytic action of dexamethasone but also that of prostaglandin E2 and isoproterenol, could be blocked in the presence of cycloheximide, an inhibitor of protein synthesis, thus suggesting that glucocorticoids and agents increasing cyclic AMP control the synthesis of some proteins involved in the triggering of cell lysis. Among the hypotheses proposed to explain the differences between in vitro and in vivo sensitivity of lymphoid cell to glucocorticoids, it was suggested that the drug may in vivo indirectly control the viability or the proliferation of thymocytes through the release of other mediators. We have shown that in vivo injection of hydrocortisone induces an accumulation of fatty acids in the whole thymus gland but not in the isolated thymocytes. Since exogenous fatty acids exert cytolytic actions on isolated thymocytes, we suggest that glucocorticoids may exert in vivo an indirect toxic action by promoting the release of fatty acids from adipose tissue or other sources.

Animals↗
PubMed1984

Role of exogenous and endogenous prostaglandins in steroidogenesis by isolated frog interrenal gland: evidence for dissociation in adrenocorticotropin and angiotensin action.

The role of prostaglandins (PGs) in the regulation of glucocorticoid and mineralocorticoid production by the frog interrenal (adrenal) gland was studied in vitro by means of continuous perifusion. No change in corticosteroid production was observed upon perifusion with PGA1 or PGA2 (up to 10(-6) M). Conversely six other primary PGs, and the prostacyclin I2 (PGI2), significantly stimulated corticosteroidogenesis: the order of potency being PGE1 greater than PGI2 greater than PGE2 greater than PGB2 greater than PGB1 greater than PGF2 alpha greater than PGF1 alpha. The ability of the PGs to stimulate corticosterone and aldosterone production indicated that PGs may contribute to corticosteroid biosynthesis and that endogenous PGs could act as mediators for certain corticosteroid-stimulating factors. The essential role of endogenous PGs for spontaneous corticosteroid biosynthesis was demonstrated by the marked inhibition of corticosterone and aldosterone production induced by indomethacin (IDM) and meclofenamic acid, two specific inhibitors of cyclooxygenase which reduced significantly PG formation in the interrenal tissue. Stimulation of steroidogenesis by ACTH or cAMP was not affected by infusion of IDM or meclofenamic acid. In addition, ACTH did not modify the production of PGs by interrenal tissue. In contrast, the stimulatory effect of the angiotensin II analog [Sar1-Val5] AII, was markedly reduced in the presence of these two PG synthetase inhibitors and a direct stimulatory effect of the AII analog on PGE2 release was demonstrated. The effects of a supramaximal dose of [Sar1-Val5] AII could not be enhanced by PGE1 indicating that the corticosteroid response to angiotensin II is dependent upon endogenous PG synthesis, whereas the additivity of the stimulatory effects of PGE1 and a maximal dose of ACTH confirmed that PGs are not involved in the mechanism of action of ACTH. These results show that endogenous and exogenous PGs are implicated in corticosteroidogenesis in the frog. Since, in fish and amphibia the adrenocortical tissue is in close contact with the kidney (a major source of PGEs) these results may suggest a physiological relationship between the kidney and the interrenal gland in lower vertebrates. In addition, our results provide the first evidence that the action of angiotensin II on both corticosterone and aldosterone production may be mediated by PGs, whereas ACTH and cAMP stimulate corticosteroidogenesis through another mechanism. Thus, our data support the concept that ACTH and angiotensin II activate the early steps of corticosteroid biosynthesis via different pathways.

Adrenal Glands↗
PubMed1984

Glucocorticoid receptors and steroid sensitivity in normal and neoplastic human lymphoid tissues: a review.

The determination of estrogen and progesterone receptors in breast cancer has been shown to be useful in predicting the response to endocrine therapy. Given their well-known inhibitory effects on lymphoid tissue, glucocorticoids have been used widely in the treatment of leukemia. Given these facts, over the last 10 years, several investigators have measured the number of glucocorticoid receptors in normal and neoplastic lymphoid tissue to see whether their number correlated with glucocorticoid responsiveness in vitro or in vivo. No clear correlation could be established between the level of glucocorticoid receptor and the in vitro action of steroids in normal and neoplastic lymphoid tissue. In contrast, attempts to correlate glucocorticoid receptor levels in acute lymphocytic leukemia to in vivo steroid responsiveness and immunological type using the whole-cell-binding assay for receptor determination and selecting the patients according to age and immunological criteria have been more successful.

Adult↗