Steinernema feltiae (= Neoaplectana carpocapsae): effect of sterols and hypolipidemic agents on development.

The structure and concentration of sterol in a lipid-defined artificial medium affected the development of the entomogenous nematode, Steinernema feltiae (= Neoaplectana carpocapsae). The nematode grew normally in vitro when the medium was supplemented with delta 5-desalkylsterol (cholesterol) or delta 5-desalkylsteryl ester (cholesterol oleate). The minimum amount of cholesterol in the medium that was necessary to support the development of S. feltiae to the climax population (i.e., dauer stage) was 0.0025%. The nematode also completed its life cycle normally when delta 0- or delta 7-desalkylsterols (cholestanol and lathosterol) were substituted for cholesterol. In contrast, development was inhibited when the medium contained delta 5,7-desalkylsterol (7-dehydrocholesterol); however, the nematode population reached the climax stage, in medium containing this sterol, when cholesterol was also present. S. feltiae was able to utilize delta 5- and delta 0-24 alpha-ethylsterols (sitosterol and sitostanol) as dietary sterols; however, when a delta 22-bond was introduced into the side chain (stigmasterol) the rate of development of the nematode slowed significantly. The growth of the nematode was also retarded when the medium contained delta 5,7,22-24 beta-methylsterol (ergosterol). The nematode population reached the climax stage in medium containing delta 8,24-4,14 alpha-trimethylsterol (lanosterol) only when cholesterol was also present. When S. feltiae was exposed to certain hypolipidemic agents, which are known to lower the level of lipids in human plasma (clofibrate, cholestyramine resin, niacin, and D-thyroxine), all but D-thyroxine affected the growth and development of the nematode in vivo (in Heliothis zea) and/or in vitro. Therefore further studies are warranted to determine how these drugs affect the lipid biochemistry of this nematode.

Effect of host insect sterols on the development and sterol composition of Steinernema feltiae.

Steinernema feltiae (= Neoaplectana carpocapsae), 'All' strain, was propagated in larvae of the corn earworm, Heliothis zea, which contained various sterols, in order to determine how the sterol composition of the host affects the growth, development and sterol composition of this insect-parasitic nematode. S. feltiae completed its life cycle normally in insects containing primarily cholesterol, cholestanol or 7-dehydrocholesterol, although the sterol composition of the dauer stage was affected by the sterol composition of the host. When the nematode was reared in insects containing primarily cholesterol, 55% of the sterol in the dauers was cholesterol and the other 46% was lathosterol. In contrast, cholestanol (70%) and lathostetrol (31%) were the sterols present in nematodes reared in H. zea containing primarily cholestanol. Cholestanol (43%), lathosterol (34%), campestanol and/or another 24-methylsterol (23%) and cholesterol (1%) were the sterols present in nematodes reared in H. zea containing campestanol and cholestanol as its major sterols. Lathosterol was the major sterol present in nematodes reared in H. zea containing principally 7-dehydrochlesterol. Therefore, in each case, S. feltiae metabolized some host sterol to lathosterol but the relative percentage of lathosterol in the nematode increased as it was exposed to delta 0-, delta 5- and delta 5,7-sterols, respectively. The ability of S. feltiae to utilize different host sterols may, in part, explain its success in parasitizing a wide variety of insects.

Sterol substrate specificity of acyl coenzyme A:cholesterol acyltransferase from the corn earworm, Heliothis zea.

The enzymatic activity and sterol substrate specificity of acyl coenzyme A:cholesterol acyltransferase (ACAT) were measured in microsomes of cells from Heliothis zea. Under standard assay conditions, the specific enzymatic activity of ACAT was highest in the intestine followed by the fat body and ovary (380.7, 30.7, 8.3 pmol/min per mg, respectively). The structure of the exogenous sterol used in the ACAT assay affected its rate of esterification. The relative rates of esterification of analogs of cholesterol with various modifications of the side chain were: 24-H greater than 24 alpha-CH3 greater than delta 22 greater than delta 24 greater than 24 alpha-C2H5 greater than 24 beta-CH3, delta 22-24 beta-CH3 and delta 22-24 alpha-C2H5. The number and position of double bonds in the B-ring of the sterol nucleus greatly affected the rate of esterification of sterols by ACAT. The average relative rates of esterification of sterols with differences in their B-rings were: delta 7 much greater than delta 8 greater than delta 0 greater than delta 5 greater than delta 5.7. The presence of a 9,14-cyclopropane group and/or methyl groups at the C-4 and 14 positions prevented significant esterification of such sterols. The formation of cholesteryl and lathosteryl esters was partially inhibited in microsomes from the intestine, fat body, and ovary by the addition of the ACAT inhibitor, 3-(decyldimethylsilyl)-N-[2-(4-methylphenyl)-1-phenylethyl]prop anamide (Sandoz Compound 58-035).(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the biological properties of androst-5-en-3 beta-ol, a series of (20R)-n-alkylpregn-5-en-3 beta-ols and 21-isopentylcholesterol with those of cholesterol.

The delta 5-sterol, androst-5-en-3 beta-ol, which has no side chain at C-17, did not permit molting of the insect Heliothis zea, growth of either the protozoan Tetrahymena pyriformis, or the yeast Saccharomyces cerevisiae adapted to anaerobic conditions, nor was the sterol esterified by a mammalian microsomal ACAT preparation. However, the sterol did form a liposome with egg lecithin and, when fed to mice, did inhibit hepatic cholesterol synthesis. 21-Isopentylcholesterol also formed a liposome but neither supported the growth of the yeast nor was metabolized by the protozoan. When sterols, 20(R)-n-alkylpregn-5-en-3 beta-ols, with side chains of varying lengths were added to the medium of the protozoan, maximal esterification with fatty acids occurred with the 20(R)-n-pentyl derivative, and maximal inhibition of tetrahymanol formation occurred with the n-butyl, n-pentyl, and n-hexyl derivatives. In all of the assays cholesterol showed a positive response, either permitting molting or growth, being metabolized, inhibiting sterol or tetrahymanol synthesis, or forming a liposome.

Cannabinoid effects on plasma corticosterone and uptake of 3H-corticosterone by mouse brain.

The effects of three cannabinoids, 11-hydroxy-delta9-tetrahydrocannabinol (11-HO-delta9-THC), delta9-THC and cannabinol (CBN), ranging in behavioral activity from high to low, were studied on two aspects of pituitary--adrenal function. Plasma corticosterone levels were used as an index of adrenocorticotropic hormone (ACTH) release. All three cannabinoids elicited an increase in plasma corticosterone elvels in a manner similar to their behavioral potency. These cannabinoids also elicited an increase in the concentration of 3H-corticosterone taken up by the brains of adrenalectomized mice in a manner similar to their potency in elevating plasma corticosterone levels. The significance and possible underlying mechanism of the apparent correlation resulting between these effects and the behavioral effects of cannabinoids are discussed.