The critical control of progesterone levels and pregnancy by antiprogesterone

Circulating plasma progesterone (P) has been quantitatively controlled in the rat "model" through highly specific binding by treatment with anti-P (A-P). Knowing the constant, which characterizes the binding of P to A-P in plasma, sequential assays of circulating A-P and A-P bound total P (Pt) revealed the levels of the biologically active unbound P (Pu). The studies showed that at different stages of gestation the mechanisms through which A-P reduces Pu and terminates pregnancy are the same. However, the doses of AP which effectively reduce Pu and also the critical levels of Pu at which pregnancy terminates are different. The moderate and transient physiologic P-withdrawal (Pw) at midterm permits the continuation of normal gestation, but pregnancy is terminated by a drastic and sustained reduction in Pu. In contrast, when Pu is only slightly and briefly reduced below physiologic levels, pregnancy continues and only retarded conceptus growth signals that Pw occurred. Apparently Pw has to be controlled and measured with "razor's-edge" precision to fully expose and define the regulatory significance of this steroid in the maintenance and termination of pregnancy. Short of this precision, the key regulator of the pregnant uterus will remain buried, as it has been during 40 years, in controversial findings.