Objectives: In order to determine the exact pattern of plasma Substance P (SP) concentration during the LH preovulatory surge and the functional correlates which could exist between plasma SP, LH, 17 beta-estradiol (E2) and Progesterone, we performed a detailed analysis of changes in plasma SP concentration, during the critical phases of the LH preovulatory surge in the Human.

Methods: The experimental study was performed in 21 women between the ages of 26 and 35 years. For each subject, blood samples were taken every 15 min, between 07:00 a.m. and 09:00 a.m. for 3 consecutive days when E2 plasma values reached at last 125 pg/ml. Then, each subject, according to the mean LH value of each day, was classified into one of the following groups: 1) the day before the day of the ascending phase, 2) the day of the ascending phase, 3) The day of the LH surge, 4) the day of the descending phase, 5) the day after the day of the descending phase.

Results: Mean SP plasma values for the day of the LH peak, the day of the descending phase and the day after the day of the descending phase were all significantly higher than the values of the day of the ascending phase. Overall, there was an almost linear increase for plasma SP values between the day before the day of the ascending phase and the day after the day of the descending phase Also,this linear increase in plasma SP concentration exhibited a positive correlation (p = 0.016) with plasma progesterone concentrations which also started to increase on the day of the ascending phase of the LH surge.

Conclusions: Taken together with previous results which have shown that the administration of a SP antagonist reduces both the amplitude and the duration of the preovulatory LH surge in the monkey, the increase in plasma SP concentrations, possibly driven by the rise in serum progesterone concentration, which take place at the time of the preovulatory LH surge, is certainly an important element of the Hypothalamo-Pituitary-Gonadal interactive network necessary for the full development of the preovulatory LH surge in the Human.