Progesterone metabolism by the hypothalamus, pituitary, and uterus of the aged rat.

Progesterone metabolism was examined in tissues of rats in three stages of reproductive senescence (constant estrus, repeated pseudopregnancies, and anestrus) and in young rats. Metabolites were quantitated by reverse isotopic dilution analysis after incubation of the hypothalamus, pituitary, and uterus with [3H]progesterone. The metabolism of progesterone to 5 alpha-dihydroprogesterone and to 20 alpha-hydroxy-5 alpha-pregnan-3-one and the formation of total 5 alpha-reduced products was significantly reduced (by half) in pituitaries of constant estrous rats compared to rats in all other stages. The formation of 3 alpha-hydroxy-5 alpha-pregnan-20-one and total 3 alpha-reduced products was about 2-fold higher in pituitaries and hypothalami of pseudopregnant and anestrous rats than in constant estrous and young rats, but these differences were statistically significant only in the pituitary samples. In the uterus, progesterone metabolism to 20 alpha-dihydroprogesterone was significantly increased in anestrous rats compared to that in constant estrous and pseudopregnant rats. The results indicate that progesterone metabolism by target tissues, particularly the pituitary, is altered during reproductive senescence. They suggest the possibility that changes in the tissue metabolism of progesterone may be one means by which the effectiveness of progesterone is decreased during aging.