Natural sex steroids and their xenobiotic analogs in animal production: growth, carcass quality, pharmacokinetics, metabolism, mode of action, residues, methods, and epidemiology.

Natural and xenobiotic compounds having sex-related actions have long been used for growth promotion and various changes in carcass quality in meat animals. The first compounds used were synthetic estrogens; however, later on a whole battery of compounds having androgenic, and progestogenic actions have also been involved. In surveying the effects of these compounds in meat-producing animals, it became clear that these drugs increase the growth rate of the treated animals and bring about changes in the carcass that are generally characterized by lower fat content and more lean mass. Extensive studies undertaken in various countries, including the European Economic Community (EEC), have shown that if used according to good husbandry practices, the meat from treated animals does not have excessive amounts of residues compared with the endogenous amount of steroid production in the animals in question and also in human beings. The banning of these compounds in the European community brought a new phenomenon of illegal or black market cocktails. These mixtures of anabolic steroids are injected into the body of the animals rather than implanted in the ears, which is the normal practice in countries where they have not yet been banned. Several screening and confirmatory methods are now available for monitoring programs. However, these programs need excessive resources in terms of manpower, funds, and proper legislation, which in underdeveloped countries is questionable, particularly in the absence of strong scientific evidence for the exercise.

The effect of feeding three anabolic steroids in different combinations on the growth, food conversion efficiency and protein and nucleic acid levels of liver, kidney, brain and muscle of mirror carp (Cyprinus carpio).

A study on the effect of three different anabolic-androgenic steroids on the growth, food conversion efficiency and nucleic acid contents of liver, kidney, brain and muscle of carp,Cyprinus carpio was undertaken. The three steroids, methyltestosterone (MT), ethylestrenol (EE) and oxandrolone (ON), were fed in different combinations at final concentrations of 5 or 6 mg/kg diet for 60 days. No effect on the growth was observed in any of the experimental groups. A decrease in the specific growth rate (11-21%) and food conversion efficiency (20-29%) was noted. Feeding of drugs increased the cranio-somatic and reno-somatic index in all except one group. Hepatosomatic (ON+MT) and viscero-somatic (ON+MT; EE+MT+ON) indices decreased. Protein increased and RNA/DNA decreased in only one group while a decrease in protein/DNA was observed in the liver of all experimental groups. RNA/DNA increased and protein/RNA decreased only in one group while no effect was seen in protein and protein/DNA contents in any of the treated kidneys. Proteins, protein/RNA and protein/DNA decreased in certain groups in brain tissue. In muscle, no effect was seen in proteins or protein/DNA. Protein/RNA decreased in all but one group while RNA/DNA was higher only in the group fed all the three steroids together.

Biological studies on indole derivatives. I. Synthesis and pharmacological studies of 2-oxo-3-indolyl derivatives.

Two compounds, 3-hydroxy-3-acetonyl-oxindole (I) and compound 3-acetonylidene-oxindole (II) were synthesized by a convenient method, and their pharmacological/toxicological effects were studied in rabbit. These compounds produced transitory effects on serum enzymes. The cholesterol mobilizing effect is more prominent with compound (I).

Biological studies on indole derivatives. I. Synthesis and pharmacological studies of 2-oxo-3-indolyl derivatives.

Two compounds, 3-hydroxy-3-acetonyl-oxindole (I) and compound 3-acetonylidene-oxindole (II) were synthesized by a convenient method, and their pharmacological/toxicological effects were studied in rabbit. These compounds produced transitory effects on serum enzymes. The cholesterol mobilizing effect is more prominent with compound (I).

Preliminary study on the effect of temperature on the transport of thyroxine (T4) into the body tissues and sub-cellular fractions of liver and muscle of carp, Cyprinus carpio.

In order to determine if the inability of thyroxine to induce cellular effects at low temperature is mediated through a temperature-sensitive system for the translocation of T4 into the nucleus, the effect of temperature on the uptake of T4 by body tissues and sub-cellular fractions of carp liver and muscle was studied in vivo. A single injection of 125I-T4 (1 micro C/10 g body weight) was given intraperitoneally to juvenile carp maintained at 15 and 25 C. Uptake from the peritoneal cavity was rapid. All the tissues exhibited maximum radioactivity at 2 hour after the injection. Fish kept at 25 C showed another peak at 8 hour and those at 15 C at 48 hour after the single injection. Transfer of T4 from the cytoplasm to nuclei was not blocked at lower temperatures. For example, in liver at 8 hour, nuclei from fish tissues kept at lower or higher temperatures had equal amounts of radioactivity. Muscle nuclei had 15% more radioactivity than liver nuclei when expressed as radioactivity/g tissue. Since there are comparable amounts of activity in the nuclei at both temperatures, some other mechanism/s than a simple block in transport from cytoplasm to nuclei is operating. There are some indications that nutritional status of fish may be playing some role in this respect.

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.

Preliminary study on the effect of temperature on the transport of thyroxine (T4) into the body tissues and sub-cellular fractions of liver and muscle of carp, Cyprinus carpio.

In order to determine if the inability of thyroxine to induce cellular effects at low temperature is mediated through a temperature-sensitive system for the translocation of T4 into the nucleus, the effect of temperature on the uptake of T4 by body tissues and sub-cellular fractions of carp liver and muscle was studied in vivo. A single injection of 125I-T4 (1 micro C/10 g body weight) was given intraperitoneally to juvenile carp maintained at 15 and 25 C. Uptake from the peritoneal cavity was rapid. All the tissues exhibited maximum radioactivity at 2 hour after the injection. Fish kept at 25 C showed another peak at 8 hour and those at 15 C at 48 hour after the single injection. Transfer of T4 from the cytoplasm to nuclei was not blocked at lower temperatures. For example, in liver at 8 hour, nuclei from fish tissues kept at lower or higher temperatures had equal amounts of radioactivity. Muscle nuclei had 15

more radioactivity than liver nuclei when expressed as radioactivity/g tissue. Since there are comparable amounts of activity in the nuclei at both temperatures, some other mechanism/s than a simple block in transport from cytoplasm to nuclei is operating. There are some indications that nutritional status of fish may be playing some role in this respect.