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Showing papers by "Michael B. Sporn published in 1975"


Journal ArticleDOI
03 Jan 1975-Nature
TL;DR: Investigation of the Biological activity of seven analogues of natural vitamin A ester (β-retinyl acetate) and vitamin A acid and found that several vitamin A analogues with alterations in the ring, including a shift of the 5,6-double bond of the cyclohexene ring to the 4,5-position and replacement of the cycle with substituted aromatic and cyclopentene rings, have substantial activity in the skin and tracheobronchial assays.
Abstract: FIFTY years after the discovery that vitamin A controls cel differentiation in epithelial tissues the mechanism involved is still unknown. The recent introduction of two-cell and organ culture systems, involving serum-free medium, for the assay of vitamin A activity in vitro may help. One assay uses epidermal cell cultures derived from mouse skin1 and the other uses tracheal organ cultures from vitamin A-deficient hamsters2. In both, the observed cellular response depends on the addition of vitamin A, which induces a marked increase in the cellular RNA of the skin cultures and a change from the production of keratin to the production of cilia and mucus in the tracheal organ cultures. We have now investigated the Biological activity of seven analogues of natural vitamin A ester (β-retinyl acetate) and vitamin A acid (β-retinoic acid), in line with the common practice of assaying physiological and pharmacological actions of vitamins, hormones and drugs using structural analogues of a parent compound. In the analogues we used, the 5,6-cyclohexenyl ring system of natural vitamin A is modified substantially. Although data obtained in vivo show that modification of the ring portion of the molecule can reduce growth-promoting activity3–5, we found that several vitamin A analogues with alterations in the ring, including a shift of the 5,6-double bond of the cyclohexene ring to the 4,5-position and replacement of the cyclohexene ring with substituted aromatic and cyclopentene rings, have substantial activity in the skin and tracheobronchial assays. Because of the sensitivity of the two assays it is now possible to assay vitamin A activity in the 10−9–10−10M range (30–300 pg ml−1). Moreover, there is excellent correlation between the results of the two assays in terms of the evaluation of Biol.ogical activity of new analogues.

161 citations


Journal ArticleDOI
TL;DR: The capacity of the alpha-isomer of retinyl acetate to support growth in hamsters fed a vitamin A-deficient diet was assessed over a 40-fold dose range and decreased relative potency was found.
Abstract: The capacity of the alpha-isomer of retinyl acetate to support growth in hamsters fed a vitamin A-deficient diet was assessed over a 40-fold dose range. Although decreased relative potency of the alpha isomer, as compared with the beta isomer, was found, sustained weight gain and survival for 6 months were achieved with a weekly intraperitoneal dose of 300 mug of the alpha isomer. An intraperitoneal dosage of alpha-retinyl acetate resulted in greater activity than an oral dosage.

12 citations