Modulation of uterine sensitivity to decidual induction in the rat by nicotinamide; challenge and extension of a model of progestational differentiation.

A recently constructed model describes pyridine nucleotide metabolism as a key target of progesterone action during early progestational differentiation of the uterus ( progestation ). The present study was designed to challenge this model. Using uterine sensitivity to decidual induction as a "whole animal" index of preimplantational differentiation, nicotinamide (NAM) was administered as a probe, to test the model's validity. Pseudopregnant rats received NAM in two injections (100 mg each, i.p.) during a 3-h interval at selected times between 1200 h on Day 2 and 1200 h on Day 4. Deciduomata were induced by intrauterine instillation of phosphate buffer between 1800 h on Day 3 and 1200 h on Day 5. Uterine sensitivity was measured indirectly as uterine weight, 5 days after induction. The effect of NAM was dependent upon the time of its administration. Maximal sensitivity (1200 h on Day 4) was not altered by injection of NAM at 1200 h on Day 2, but was inhibited by 60% following injection at 1200 h on Day 3. After this period, the inhibitory effect of NAM was diminished. When NAM was injected at 1200 h on Day 4, a slight, but significant, augmentation of sensitivity was measured. These responses were predicted by the model. A comparison of the effects of NAM with those of progesterone suggested a mechanism of action for the hormone during early progestation .