Differentiation of the uterus in preparation for gestation: a model for the action of progesterone.

During the preimplantation stages of pregnancy, rising titers of progesterone alter the metabolism of the uterine endometrium to permit implantation of the blastocyst. In this model of progestational differentiation, it is proposed that endometrial pyridine nucleotide metabolism is a key target of progestogen action. The hormone may modulate NAD metabolism to promote NADP synthesis while inhibiting NAD breakdown to ADP ribose and nicotinamide. The result of such an action would impair uterine DNA synthesis and cell division, but provide increased NADP for coenzyme-limited synthetic processes and cytodifferentiation. As a result, the endometrium differentiates and becomes sensitive to decidual-inducing stimuli (the blastocyst). The decidual stimulus reverses the process by rapidly inhibiting NADP production, and by dramatically increasing poly ADP ribosylation of nuclear protein, thus facilitating DNA synthesis and the wave of cell division associated with the initiation of decidualization. The background information and evidence in support of this model are presented.