Regulation of acetyl-CoA carboxylase in rat mammary gland. Effects of starvation and of insulin and prolactin deficiency on the fraction of the enzyme in the active form in vivo

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Abstract
The ''initial'' (I), endogenous phosphatase-activated (A) and citrate-activated (C) activities of acetyl-CoA carboxylase were measured in mammary-gland extracts of pregnant and lactating rats. There was a 10-fold increase in the A and C enzyme activities in the transition from early to peak lactation, but there was no significant increase in the ratio of the initial activity to the A and C activities of the enzyme. Starvation (24 h) or short-term (3 h) streptozotocin-induced diabetes both resulted in a 40% decrease in I/A and I/C activity ratios. In starvation this was accompained by a decrease in the absolute values of the A and C activities such that the initial activity in mammary glands of starved animals was 45% that in glands from fed animals. Insulin treatment of starved or diabetic animals 60 min before killing increased the I activity without affecting the A or C enzyme activities. Removal of the pups for 24 h from animals in peak lactation (weaning) resulted in a marked but similar decrease in all 3 activities such that, although the initial activity was only 10% of that in suckled animals, the I/A and I/C activity ratios remained high and unaltered. Inhibition of prolactin secretion by injection of 2-bromo-.alpha.-ergocryptine gave qualitatively similar results to those during weaning. Simultaneous administration of ovine prolactin completely prevented the effect of bromoergocryptine. The initial activity of acetyl-CoA carboxylase in rat mammary gland apparently is regulated by at least 2 parallel mechanisms: an acute regulation of the proportion of the enzyme in the active state and a longer-term modulation of enzyme concentration in the gland. Insulin appeared to mediate its acute effects through the 1st mechanism whereas prolactin had longer-term effects on enzyme concentratoin in the gland. A comparison of initial enzyme activities (I) obtained in the present study with rates of lipogenesis measured in vivo gave good agreement between the 2 sets of data for all conditions studied except for 24 h-starved and streptozotocin-diabetic animals. Acetyl-CoA carboxylase activity apparently is rate-limiting for lipogenesis in the mammary gland in normal, fed, suckled or weaned animals but in starved and short-term diabetic animals changes in the activity of the enzyme by covalent modification alone may not be sufficient to maintain the enzyme in its rate-limiting role.

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