Abolition of the diethylstilbestrol reduction of enzyme leakage from muscle by a 3,3' diallyl substitution. 1977

L Cohen, and J Morgan, and S Bittner, and M E Bozyk

Diethylstilbestrol (DES) lowers enzyme efflux from isolated mouse skeletal muscle. It also lowers the high serum enzyme activities in Duchenne's muscular dystrophy. We have begun a systematic study of DES congeners, to identify those portions of the DES molecule which are critical to these effects, and to tailor a molecule which might have fewer feminizing effects. The first compound tested was the 3,3' diallyl derivative of DES (DAS). It was selected because previous reports indicated that it was as anabolic as DES, but only 1/10 to 1/30 as estrogenic. Doses of 20, 100 and 250 microgram/mouse/day were administered in 0.05 ml sesame seed oil vehicle to C57BL/6 mice. Control animals received only the vehicle. In contrast to DES which has consistently reduced muscle enzyme efflux 30-50%, DAS was inert. The substitution of the two allyl groups in the 3 and 3' positions blocks access to the neighboring ethyl groups and partially covers the two phenolic hydroxyl groups of DES. This suggests that these molecular sites have pertinence to the reduction of enzyme efflux from mouse skeletal muscle by DES, and possibly the reduction of the high serum enzyme activities in Duchenne's muscular dystrophy.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D004054 Diethylstilbestrol A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed) Stilbestrol,Agostilben,Apstil,Diethylstilbestrol, (Z)-Isomer,Diethylstilbestrol, Disodium Salt,Distilbène,Stilbene Estrogen,Tampovagan,Estrogen, Stilbene
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D000498 Allyl Compounds Alkenes with the general formula H2C Compounds, Allyl
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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