The effects of pregnenolone sulfate and ethylestrenol on retention of a passive avoidance task.

Two experiments using male rats evaluated the effects of a range of doses of the neurosteroid, pregnenolone sulfate (PS), or of the synthetic neurosteroid, ethylestrenol (E), on the retention of a passive avoidance task. The steroids either were given immediately after the training trial or 1 h before the first retention test. Retention tests were given both 24 h and 48 h after acquisition. In both experiments, separate groups of animals were trained under low or moderate footshock conditions. At all doses tested both PS and E improved retention under the low footshock conditions. In groups trained with the higher footshock, the steroid-treated groups performed no better than the vehicle controls. Indeed, there were suggestions that some doses impaired retention. These results seem best understood as an induction of bimodality or 'turbulence' in behavior as used in Chaos theory rather than a shift in an inverted U-shaped retention function. In the second experiment in which the steroids were given before retention testing, they were generally without effect.

Effects of steroids with different endocrine profiles on the development, morphology and function of the bursa of Fabricius in chickens.

This paper describes the effect of various steroids on the anlage of the bursa of Fabricius in chickens. The steroids were administered by dipping embryonated eggs on the third day of incubation in ethanolic solutions of these steroids. The results with about 30 different steroids show that the capacity to inhibit the development of the bursa does not correlate with the endocrine properties of these steroids as measured in routine screening tests for androgenic, anabolic, progestational and oestrogenic activities or with the relative binding affinities for various endocrine receptors. More elaborate studies with several representative steroids show that testosterone (10 mg/ml), nandrolone (10 mg/ml), 11 alpha-hydroxynandrolone (10 mg/ml), ethylestrenol (1 mg/ml), lynestrenol (1 mg/ml), and Org OD14 [tibolone] (0.1 mg/ml) induce also histomorphological changes in the remaining bursa tissue still present in 10 day- and 53-day old chickens and in the bursa-dependent sites of their spleens (53-day old chickens only). Testosterone and lynestrenol induced smaller changes than nandrolone or ethylestrenol. Tibolone and 11 alpha-hydroxynandrolone were more effective than nandrolone. All drugs, except testosterone and lynestrenol, imparied antibody formation to Newcastle Disease Virus and decreased the serum levels of total IgG, but not of total IgM. Also these effects were not correlated with endocrine properties. In other studies (for references, see text) we found that several of these steroids, notably tibolone, favourably influence the course of spontaneous autoimmune diseases of NZB/W mice and Obese Strain chickens. Since this autoimmunosuppression is likely to be caused by inhibitory effects on bursa or bursa equivalent, we may use this approach for developing medically useful autoimmunosuppressive steroids with minimal endocrine effects.

Cellular growth responses of rainbow trout (Salmo gairdneri) fed different levels of dietary protein, and an anabolic steroid ethylestrenol.

Cellular growth responses of rainbow trout (Salmo gairdneri) fed different levels of dietary protein (35, 45, and 55%), with and without the anabolic steroid ethylestrenol, have been studied over a 60-day period. With an increase in dietary protein, total liver proteins increased in fish fed the steroid-free (control) diets, whereas no change occurred in the other tissues. Muscle and spleen RNA was unchanged, but RNA increased in liver, kidney, and brain. The DNA content increased in muscle, decreased in brain, but remained constant in liver, kidney, and spleen. Feeding the ethylestrenol-supplemented (experimental) diets resulted in an increase in total proteins, RNA, and DNA of kidney over the respective control value at each level of dietary protein. In the other tissues, total proteins and DNA were essentially unchanged, but total RNA content decreased in liver and increased in muscle in the experimental groups. It is concluded that in trout, the dietary protein level exerts marked differential effects on cellular growth parameters (RNA/DNA, RNA/protein, protein/DNA), which are further modified by steroid treatment. Evidence that cellular growth responses in muscle keep pace with total body growth was also indicated.

[Non-enzymatic fibrinolytic agents]. / Les agents fibrinolytiques non enzymatiques.

Non-enzyme fibrinolytic agents include pharmacological agents which are active in vivo but inactive in vitro and synthetic chemical compounds which when added to blood or plasma in vitro directly induce fibrinolysis. There are a number of drugs with a short duration of action such as adrenalin, nicotinic acid, vasopressin and histamine. Vasoactive drugs probably act by stimulating the liberation of vascular activator. The effect of nicotinic acid is rapidly exhausted when injections are repeated. By contrast, the biguanides and certain anabolic steroids are capable of exerting a long term stimulation of endogenous fibrinolysis. Amongst these substances, phenformin, metformin, ethyloestrenol, stanozolol and a new substance, moroxydine chloride, have been studied. The biguanides appear to be capable of exerting an effect upon the synthesis and liberation of plasminogen vascular activator. The combination of an anabolic steroid and a biguanide would appear to be the most powerful. These various drugs have been used with success in cases of recurrent venous thrombosis in patients with an abnormally low level of plasminogen activator in the venous walls and/or low fibrinolytic activity after venous stasis. Chemical fibrinolytic agents were studied only in vitro, since the use of these substances in human therapeutics would seem to be still difficult in view of the fact that they are active only in a narrow range of concentrations.

Comparison of protective effects of ethylestrenol, norbolethone, and spironolactone against lethality from acute doses of parathion and paraoxon in female rats.

Protection against the toxicity of parathion (increased LD50) was provided by preadministered ethylestrenol and, to a lesser extent, by norbolethone and spironlactone. Ethylestrenol and norbolethone also offered protection against paraoxon toxicity. With ethylestrenol and spironolactone, the protection against parathion lethality was greater than that against paraoxon lethality.

Effect of anabolic steroids on plasma antithrombin III. alpha2 macroglobulin and alpha1 antitrypsin levels.

The effect of seven different anabolic steroids (Ethyloestrenol, Methenolone acetate, Norethandrolone, Methylandrostenediol, Oxymetholone, Methandienone, and Stanozolol) on three alpha-globulin antiprotease inhibitors of thrombin and plasmin was studied in men with ischaemic heart disease. In distinct contrast to the oral contraceptives, five of the six 17-alpha-alkylated anabolic steroids studied produced increased plasma Antithrombin III levels and five produced decreased levels of plasma alpha2-macroglobulin. The effect on plasma alpha1-antitrypsin levels was less clear-cut but three of the steroids examined produced significantly elevated levels. The increased plasma fibrinolytic activity which the 17-alpha-alkylated anabolic steroids induce is therefore unlikely to be secondary to disseminated intravascular coagulation.

Effect of protein hormones and steroids on tissue cultures of endometrial carcinoma.

Neoplastic tissue was obtained from 30 patients with endometrial carcinoma and the response of this tissue to various hormones was studied in vitro by histological methods and by measuring the incorporation of 3-H thymidine into DNA. Progesterone and synthetic progestogens had a consistently adverse effect on tissue survival in vitro while pregneolone had a beneficial effect.