Pulsatile cosecretion of estradiol and progesterone by the midluteal phase corpus luteum: Temporal link to luteinizing hormone pulses

Using recently defined analytical tools that permit quantitative and integrated assessments of pulsatile activities of two or more hormones, we have examined the coincidence of pulses of estradiol (E₂), progesterone (P₄), and LH determined in blood withdrawn at 15-min sampling intervals for a duration of 24 h in each of 15 women during the midluteal phase of the human menstrual cycle. The occurrence of E₂ and P₄ pulses is simultaneous, as their peaks were maximally correlated at zero time lag (P < 10^-4), and there were comparable periodicities for E₂ (13.5 ± 0.7 pulses/24 h) and P₄ (11.2 ± 0.7 pulses/24 h). This coupling of E₂ and P₄ pulses suggests cosecretion by the mature corpus luteum. These E₂ and P₄ pulses are significantly coupled with LH pulses, with a lag time of about 30 min and/or 45 min for P₄ (P = 0.029) and 0 min and/or 15 min for E₂ (P = 0.032). Further, when considered together, LH, E₂, and P₄ are found to be triply copulsatile (P = 0.0066). However, significant numbers of discrete pulses of P₄ and E₂ are observed without antecedent LH pulses, suggesting some degree of corpus luteum autonomy. In conclusion, orchestrated synchrony of pulsatile pituitary and ovarian (corpus luteum) signaling can be demonstrated by the coordinated temporal release of LH, E₂, and P₄ in normal cycling women.