The control of sterol synthesis during development of rabbit mammary gland.
A 9-fold increase in the rate of conversion of [14C]-acetate to nonsaponifiable lipids was seen on culturing explants of pregnant rabbit mammary gland in the presence of insulin, prolactin, and cortisol. Stimulation of [3H]mevalonate into nonsaponifiable lipid was 3-fold under the same conditions. With both substrates activities were maximal after 24 h in culture. Incorporation of acetate into saponifiable lipid was stimulated 20-fold after 24 h and almost 50-fold after 48 h in the presence of hormones. Radioactivity from [3H]mevalonate was incorporated into saponifiable lipid after 48 h in culture with hormones suggesting an active trans-methyl-glutaconyl shunt at this time. Changes in the rate of acetate conversion to nonsaponifiable lipid correlated well with the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) in the glands of mid-pregnant and mid-lactating rabbits. Enzyme activity rose from 3.3 pmol/min/mg of 100,000 X g pellet protein in the mid-pregnant gland to an apparent value of 15.6 pmol/min/mg of 100,000 X g pellet protein in the lactating gland. When corrected for the very high content of milk protein in this 100,000 X g pellet, the HMG-CoA reductase activity was 36-fold greater in lactating compared to pregnant mammary gland. Hepatic reductase in both pregnant and lactating animals was approximately 25 pmol/min/mg of microsomal protein. This increase in capacity for sterol synthesis in mammary gland during the transition from pregnancy to lactation suggests that this tissue could synthesize a major proportion of milk sterol.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D007774:Lactation; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000502:physiology*; D008798:Mevalonic Acid / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology; D011817:Rabbits; D013261:Sterols / Q000096:biosynthesis*
D000085:Acetates; D007328:Insulin; D013261:Sterols; D011388:Prolactin; D008798:Mevalonic Acid; D006854:Hydrocortisone