INVIVO UPTAKE OF [PROGESTERONE-H-3 AND [H-3]-5-ALPHA DIHYDROPROGESTERONE BY RAT-BRAIN AND PITUITARY AND EFFECTS OF ESTRADIOL AND TIME - TISSUE CONCENTRATION OF PROGESTERONE ITSELF OR SPECIFIC METABOLITES

The present study reports the selective accumulation of progesterone and specific metabolites of progesterone by hypothalamus, anterior pituitary, midbrain, pineal, cerebellum, cerebral cortex, uterus, muscle, and plasma 10 and 30 min after iv injections of [3H]progesterone or [3H]-5α-dihydroprogesterone (5α-DHP) into ovariectomized rats and 10 min after injection of these 3H-labeled steroids into ovariectomized, estrogen- primed rats. The accumulated 3H in plasma and tissues was examined by reverse isotopic dilution analysis for levels of progesterone, 5α-DHP, 3α-hydroxy-5α-pregnan-20-one, 20α-dihydroprogesterone, 20α-hydroxy-5α-pregnan-3-one, and 5α-pregnane- 3α, 20α-diol. After 5α-DHP injections, there was no tissue 3H associated with progesterone or 20α-dihydroprogesterone. Significant differences were observed among tissues in the steroidal compounds that were accumulated at concentrations greater than those found in plasma, cerebral cortex, and muscle. The anterior pituitary and midbrain selectively accumulated [3H]-5α-DHP after injection of either [3H]progesterone or [3H]- 5α-DHP. There was no selective accumulation of [3H]progesterone by anterior pituitary or midbrain relative to plasma, cerebral cortex, or muscle accumulation. There were small selective accumulations in the pituitary of 3α-hydroxy-5α-pregnan-20-one, 20α-hydroxy-5α-pregnan-3-one, and 5α-pregnane-3α, 20α-diol but not after [3H]-5α-DHP injections. The hypothalamus, on the other hand, accumulated significant amounts of both [3H]progesterone and [3H]-5α-DHP but no others. The pineal had the greatest accumulation of [3H]progesterone compared to all othertissues, but 5α-DHP was not similarly elevated after [3H]progesterone injection. The pineal also had higher accumulations of the 20α series of metabolites after injection of either [3H]progesterone or [3H]-5α-DHP. The uterine results agree with previous studies, since there was significant accumulation of progesterone only with estrogen priming. There was little uterine accumulation of 5α-DHP in any group. These results suggest that the diverse effects of progesterone may result from progesterone per se, metabolites or combinations of these two. © 1979 by The Endocrine Society.