Endocrine Abstracts

During the luteal phase of the menstrual cycle aldosterone increases mainly due to the antagonistic properties of progesterone at the MR and due to estrogen-mediated stimulation of angiotensinogen. Little is known about other steroid-metabolizing enzymes that may influence steroid receptor binding, eg 11beta-HSDs, A-ring reductases. Therefore a group of ten normotensive female volunteers with regular menstrual cycles were studied on day 7 (follicular phase) and day 21 (luteal phase) of their menstrual cycle. Urinary steroids were measured with gas chromatography/mass spectrometry.

Pregnanediol (mean plus/minus SD; 480plus/minus438 microg/24h vs 2226plus/minus1200 microg/24h, p<0.005), 5-pregnantriol (583plus/minus188 microg/24h vs 907plus/minus350 microg/24h, p<0.05) and 17-hydroxy-pregnenolone (147plus/minus134 microg/24h vs 308plus/minus135 microg/24h, p<0.01) increased significantly as expected. Increased excretion of 3alpha,5beta-tetrahydro(TH)-aldosterone during the luteal phase (41plus/minus15 microg/24h vs 63plus/minus34 microg/24h, p<0.05) was indicative of an increased luteal aldosterone secretion. We did not observe differences in total cortisol metabolites, in 11beta-HSD2 activity (indicated by the urinary free cortisol/cortisone (F/E) ratio) or 11beta-HSD1 activity (indicated by the urinary (THF+allo-THF)/THE ratio) across the menstrual cycle. However, we did observe increased 5alpha-reductase activity reflected by absolute levels of 5alpha-metabolites and reductions in TH-corticosterone/5alpha-TH-corticosterone (0.77plus/minus0.42 vs 0.62plus/minus0.31, p<0.01) and THF/allo-THF ratios (2.62plus/minus1.54 vs 2.35plus/minus1.55, p<0.05) in the luteal phase.

It is not clear if this increase in 5alpha-reduction during luteal phase is mediated by 5alpha-reductase type 1 or 2 and what are possible triggers for its stimulation. Paradoxically an increase in 5alpha-reductase activity has been reported by our group and others in annovulatory patients with PCOS so it is unlikely to be progesterone mediated. Recent studies also report activity of some 5alpha-F metabolites upon the GR. 5alpha-reductase type 1 is the principal enzyme in human liver, fat and kidney; tissue-specific differences in the activity of this enzyme might account for some of the physiological and pathophysiological changes seen across the menstrual cycle.