INVIVO UPTAKE AND METABOLISM OF [H-3]PROGESTERONE AND [H-3]5-ALPHA-DIHYDROPROGESTERONE BY RAT CNS AND ANTERIOR-PITUITARY - TISSUE CONCENTRATION OF PROGESTERONE ITSELF OR METABOLITES

In mammals, progesterone has diverse effects which could result from the action of progesterone itself and/or specific metabolites. In neuro-endocrine tissues, progesterone is rapidly metabolized principally to 5α-dihydroprogesterone and 3α-hydroxy-5α-pregnan-20-one, and it is unclear whether progesterone and/or metabolite.(s) mediate cellular responses. Below we report on the selective tissue accumulation of progesterone and certain of its metabolites. [3H]-progesterone or [3H]-5α-dihydroprogesterone (5α-DHP) was injected intravenously (i.v.) into ovariectomized rats for 10 or 30 min or into oestrogenprimed ovariectomized rats for 10 min. Isotopic dilution analyses of the accumulated tritium in plasma and selected tissues were made for progesterone, 5α-DHP, 3α-hydroxy-5α-pregnan-20-one, 20α-dihydroprogesterone, 20α-hydroxy-5α-pregnan-3-one and 5α-pregnane-3α, 20α-diol. Significant differences between tissues were noted in terms of which steroidal compounds were accumulated above plasma and non-target tissue levels. The pituitary accumulated large amounts of [3H]-5α-DHP from either injected steroid but progesterone levels did not differ from plasma and non-target tissues. The hypothalamus accumulated significant amounts of both 5α-UHP and progesterone in all groups. The midbrain-tectum accumulated 5a-DHP comparable to hypothalamus and pituitary levels in all groups after injection of either steroid. The pineal had the greatest accumulations of progesterone in all groups but there were no accumulations of 5α-DHP above non-target tissue levels following [3H]-progesterone injections. The pineal also accumulated some 20α-metabolites. In uterus there was significant accumulation of progesterone only with oestrogen priming and little accumulation of 5α-DHP. These results and others suggest that the diverse effects of progesterone may result from progesterone per se, from metabolites or from combinations. © 1979.