title: A mevalonate requirement for maintenance of fatty acid and protein synthesis during hormonally stimulated development of mammary gland in vitro.
abstract: The effect of compactin on hormonally induced lipogenesis and protein synthesis was studied in vitro in explants of mammary gland from mid-pregnant rabbits. Compactin blocks mevalonate synthesis by the specific inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase, and in this system, culture with 10 microM compactin for 24, 48, and 72 h inhibited incorporation of [1-14C]acetate (but not [2-14C]mevalonate) into sterol by 98, 95, and 86%, respectively. Removal of compactin prior to assay rapidly reversed this effect and was associated with increased tissue 3-hydroxy-3-methylglutaryl-CoA reductase activity. Fatty acid synthesis (measured by incorporation of [1-14C]acetate or [4,5-3H]leucine) and protein synthesis (measured by incorporation of [4,5-3H]leucine) were both inhibited by around 50% after culture with compactin. This inhibition was not rapidly reversed by removal of compactin prior to assay, but it was prevented by inclusion of 1 mM mevalonolactone in the culture medium. After removal of compactin and continued culture in its absence for 24 h with hormones, the normal tissue capacity for fatty acid and protein synthesis was restored, indicating no permanent cell damage. The results suggest a specific requirement for mevalonate (or derived products) for the hormonal maintenance of the increased fatty acid and protein synthesis characteristic of the development of the mammary gland.
mesh_terms: D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000818:Animals; D002250:Carbon Radioisotopes; D005227:Fatty Acids / Q000096:biosynthesis*; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives*; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000502:physiology*; D008798:Mevalonic Acid / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D009281:Naphthalenes / Q000494:pharmacology; D009924:Organ Culture Techniques; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011817:Rabbits; D014316:Tritium
chemical_list: D000085:Acetates; D002250:Carbon Radioisotopes; D005227:Fatty Acids; D007328:Insulin; D009281:Naphthalenes; D014316:Tritium; C012258:mevastatin; D011388:Prolactin; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D007930:Leucine; D019342:Acetic Acid; D008798:Mevalonic Acid