Biomedical subjects

J M Fayard

Publications and source records attributed to J M Fayard.

At least 37 records · Page 2Linked to original sources

PubMed1991

Dissociated effects of tamoxifen on growth and on progesterone receptor induction in quail oviduct.

The estrogen agonist and antagonist activities of tamoxifen on growth and progesterone receptor induction were studied in the immature quail oviduct. Tamoxifen alone, when administered for 3 days at doses ranging from 0.01-10 mg/kg, had no effect on oviducal weight, DNA, and protein content, but significantly increased progesterone receptor concentration. When combined with estradiol benzoate (0.1 mg/kg daily for 3 days), tamoxifen completely inhibited the trophic action of estradiol while it only reduced the progesterone receptor concentration in the oviduct by 50%. This latter effect reflected more a reduction in the progesterone-responsive cell population of the tissue rather than a true estrogen antagonist effect on this specific protein induction. These results and previous data from this laboratory support the conclusions that in this model system: (1) the mechanisms involved in the induction of estrogen-sensitive cell proliferation and progesterone receptor synthesis are independent, and (2) the estrogen-antagonist activity of tamoxifen on cell proliferation is mediated through an estrogen receptor-independent pathway. Thus, the immature quail oviduct model system is particularly relevant to more detailed studies on the molecular modes of action of synthetic antiestrogens.

Animals↗

PubMed1991

Growth inhibition and the regulation of cyclic AMP by the triphenylethylene anti-estrogen tamoxifen in the quail oviduct.

The aim of the present study was to investigate the regulation of cAMP by tamoxifen in quail oviduct. A single injection of tamoxifen to immature female quails induced a transient activation of adenylate cyclase. Enzyme activity began to increase 3 h after the injection, peaked at 6 h and then dropped to control level at 12 h. The same time-response curves were observed following the injection of estradiol benzoate or estradiol benzoate + tamoxifen. Moreover, adenylcyclase exhibited the same sensitivity to exogenous activators (guanylylimidodiphosphate and forskolin) in the different treated groups. Phosphodiesterase activity was left unchanged during the prereplicative period and cAMP concentration was significantly increased at 6 h (+ 44.3%). Then, cAMP concentration continued to increase (+ 73.8% at 24 h) while cAMP phosphodiesterase and adenylcyclase activities remained at control levels. Injected concurrently with estradiol benzoate, tamoxifen completely inhibited the growth promoting effect of estradiol. Tamoxifen also inhibited the activation of adenylcyclase and cAMP phosphodiesterase induced by the hormone alone during the proliferative phase of the tissue. Moreover, the combined treatment led to a sustained elevation of cAMP in the oviduct, whereas estradiol benzoate alone decreased the level of cAMP. These results and those of our previous studies showing a significant correlation between the growth inhibitory potency of triphenylethylene derivatives in vivo and their efficiency to inhibit calmodulin-dependent cAMP phosphodiesterase in vitro, strongly suggest that the differential regulation of cAMP levels by estradiol and tamoxifen is essential for the growth promoting or growth inhibiting activities of these molecules.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1989

Effects of tamoxifen, tamoxifen metabolites, and nafoxidine on adenosine 3',5'-monophosphate phosphodiesterase: correlations with growth inhibitory activities but not estrogen receptor affinities.

Triphenylethylenes [Tamoxifen (TAM), TAM metabolites, and nafoxidine] were found to inhibit Ca2+-calmodulin (CaM)-dependent cAMP phosphodiesterase (PDE) activity of the quail oviduct, whereas 17 beta-estradiol was inactive. The Ca2+-CaM-independent PDE activity was not affected by triphenylethylenes, suggesting that they do not interact directly with the active site of the enzyme. Kinetic analysis indicated that these drugs competitively inhibited the activation of PDE by CaM with the following potencies: N-desmethyltamoxifen, Ki = 3 microM; metabolite Z, trans-4-hydroxytamoxifen, and TAM Ki = 5 microM; nafoxidine, Ki = 8.5 microM; and metabolite Y and cis-4-hydroxytamoxifen, Ki = 50 microM. Injected alone into immature quails, none of these drugs significantly affected oviduct weight. When administrated together with estradiol benzoate, these drugs reduced the trophic effect of estradiol in a dose-dependent relationship, with ID50 values ranging from 0.07 mg/kg for N-desmethyltamoxifen to 2.02 mg/kg for cis-4-hydroxytamoxifen. The order of growth inhibitory potency was not correlated with estrogen receptor affinities, but was the same as that reported for PDE inhibition. This correlation suggests that interaction of antiestrogen with Ca2+-CaM dependent PDE may be one of the mechanisms responsible for the estrogen antagonist activity of these drugs.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1976

[Long-term fate of mitral valve prostheses].

The long term fate of mitral valve replacements (over 2 years) has been studied by the collection of information from many French cardiology centres. The Starr valve with a plastic ball-valve is by far the most commonly used prosthesis. The late complications are dominated by thrombo-embolic sequelae. The functional result seems to be proportionally better the earlier the stage at which the operation is carried out.

Adolescent↗

PubMed1975

[Unruptured aneurysms of Valsalva sinus of septal origin].

Aneurysms of Valvsalva sinus unruptured into a cavity, but developing into the membranous and even muscular interventricular septum are exceptional. Two cases illustrating this fact are reported. In one of them, a massive mitral incompetence by elongated chordae tendinae related to the presence of a voluminous intra-septal pouch. Atrio-ventricular and intraventricular conduction disturbances were present in both patients. The interest of supra-valvar angiography which makes it possible to advise operation before the eventual rupture is underlined.

Adult↗

PubMed1974