Nicotinamide Adenine Dinucleotide Kinase in the Rat Uterus: Regulation by Progesterone and Decidual Induction*

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Abstract
Nicotinamide adenine dinucleotide (NAD) kinase(ATP:NAD+ 2′ phosphotransferase; EC 2.7.1.23) activity was measured in uterine endometrium from hormone-treated, chronically ovariectomized rats. After 3 days of priming with 5 μg estrone/day and 1 day of hormone deprivation (day 0), animals were injected daily for 1–5 days with (1) no hormone (C), (2) 1 ng estrone (E), (3) 2 mg progesterone (P), or (4) the two hormones combined (E+P). Decidual induction in similarly treated rats demonstrated the ability of the E+P treatment to generate a transient period of decidual sensitivity comparable to that of normal pseudopregnancy. NAD kinase activity was measured during days 2 through 6 of treatment and, additionally, 30 min after decidual induction on day 5 in animals treated with E, P, or E+P and on day 6 in animals with E+P. Kinetic parameters of NAD kinase were assessed on day 5 of treatment with E or E+P or 30 min after uterine trauma on day 5 of E+P treatment. NAD kinase activity increased over time after P and E+P treatments, but not after treatment with E. Uterine trauma inhibited enzyme activity in P- or E+P-treated rats regardless of the ability of the uterus to respond to the decidual induction; by contrast, no inhibition of enzyme activity occurred after trauma during E treatment. Thus, inhibition of NAD kinase activity after trauma was progestogen dependent but not directly related to decidual induction. Kinetic analyses showed that the values for apparent Km and maximum velocity for NAD kinase were identical when measured during E or E+P treatments. However, decidual induction during E+P treatment increased the apparent Km 30% and decreased the maximum velocity 48%, suggesting that the reactivity and perhaps the affinity of the enzyme for NAD+, the substrate, were rapidly and dramatically inhibited. Thus, though progesterone stimulates NAD kinase over time, perhaps via regulation of gene expression and specific protein synthesis, uterine trauma inhibits enzyme activity, apparently through a more direct and rapid effect on the progesterone-stimulated enzyme.