Effects of Adrenalectomy, Adrenalectomy–Ovariectomy, and Cortisol and Estrogen Therapies Upon Enzyme Activities in Lactating Rat Mammary Glands

Abstract

The effects of adrenalectomy and adrenalectomy–ovariectomy on the 5th day of lactation followed by cortisol and estrogen therapies on enzyme activities in rat mammary glands were investigated. This stage of lactation was selected because mammary secretory cell proliferation is essentially complete at this time thereby enabling study of the effects of cortisol and estrogen on enzyme levels in a nonproliferating secretory cell population. Eighteen enzymes were selected for study on the bases of their respective roles in milk biosynthesis and carbohydrate and energy metabolism and/or on the basis of previous studies indicating that their activities increase during midlactation or are regulated, in part, by steroid hormones. After adrenalectomy on the 5th day of lactation, cortisol therapy was required for normal increases in the activities of succinic dehydrogenase, citrate cleavage enzyme, malic enzyme, UDPglucose pyrophosphorylase, UDPglucose 4-epimerase, and glucose-6-phosphate dehydrogenase. The activities of UDPglucose pyrophosphorylase and glucose-6-phosphate dehydrogenase were higher than normal in cortisol-treated animals. Cortisol therapy during the last 2 days of the experiment increased the activity of UDPglucose pyrophosphorylase and possibly citrate cleavage enzyme. The activities of α-glycerolphosphate dehydrogenase, phosphoglucomutase, 6-phosphogluconate dehydrogenase, pentose phosphate metabolizing ability, hexokinase, phosphofructokinase, fructose-1,6-diphosphate aldolase, pyruvate kinase, lactic dehydrogenase, aspartate aminotransferase, isocitrate dehydrogenase, and extramitochondrial malate dehydrogenase were not notably affected by adrenalectomy or cortisol therapy. The activities of 6-phosphogluconate dehydrogenase, pentose phosphate metabolizing ability, phosphofructokinase, and pyruvate kinase may have increased after the 5th day of lactation in adrenalectomized as well as in normal animals. Combining ovariectomy with adrenalectomy reduced pup weight gains more than adrenalectomy alone, but did not further decrease significantly the activities of any of the enzymes measured. Ovariectomy had no effect when cortisol was administered. Cortisol therapy completely reversed adverse effects of estrogen given to adrenalectomized–ovariectomized animals. On the bases of these and previous data, it was concluded that cortisol regulates the rates of synthesis of several mammary gland enzymes during midlactation.