DISAPPEARANCE AND UNEXPECTED REAPPEARANCE OF PROGESTERONE IN THE CIRCULATION OF THE MONKEY - NOVEL HORMONE KINETICS

1. Intravenous injection of [H-3]progesterone in non-pregnant monkeys resulted in total disappearance of the labelled hormone from the circu lation within 3 h. However, 0.5-1.75 h after disappearance the hormone reappeared, reaching 20% (median, 5%) of the initial maximal concentr ation. 2. Reappearance of labelled hormone was accompanied by similar fluctuations in the levels of labelled metabolites, [H-3]20 alpha-dihy droprogesterone and [H-3]17 alpha-hydroxyprogesterone, which reached 6 1% (median, 14%) and 120% (median, 13%), respectively, of the initial maximal concentrations. 3. Chromatography was used to separate labelle d progesterone and its metabolities. Efficiency of the procedure was d etermined separately in each sample and for each steroid. All data wer e corrected for percentage recovery. 4. Analytical equations were devi sed, based on the theory of compartmental systems with continuously di stributed time lags, to describe the unexpected kinetics of progestero ne levels. The coefficients of determination ranged from 86 to 99% (me dian, 96%) which indicates that the equations enabled reliable predict ion of hormone levels in blood within the time range studied. 5. The u nexpected reappearance of labelled progesterone cannot be explained by hormone secretion but only by a delayed release from tissue stores, s ince progesterone does not undergo enterohepatic recirculation. Thus, a previously undescribed mechanism affecting circulating progesterone levels, and perhaps those of other hormones, exists.