Brain neurosteroids during the mouse oestrous cycle

Concentrations of the neuroactive steroid 3alpha,5alpha-tetrahydroprogesterone (TH PROG or allopregnanolone) and its precursors progesterone (PROG) and 5alpha-dihydroprogesterone (DH PROG) have been measured in mouse brain throughout the oestrous cycle. Plasma PROG concentrations were also measured for comparison. At each stage, circadian fluctuations were found in the concentrations of brain PROG and its metabolites. Such fluctuations were greater than those attributable to any particular stage of the oestrous cycle. Over the entire cycle, a significant correlation was found between brain TH PROG (or DH PROG) and PROG concentrations but not between brain TH PROG (or DH PROG) and plasma PROG concentrations. There was also no correlation between endogenous TH PROG (or DH PROG) and activity of the 5alpha-reductase converting 3H-PROG to 3H-DH PROG in whole brain homogenates. Concentrations of another neuroactive steroid, pregnenolone sulphate (PREG S), in the brain during the oestrous cycle were in phase with plasma PROG but not brain PROG concentrations. Our results indicate that circadian and ovarian influences on the concentrations of PROG and its metabolite TH PROG in female whole mouse brain are caused predominantly by changes in the supply of PROG from within the tissue, whatever the contribution of peripheral sources.