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Pulsatile Cosecretion of Estradiol and Progesterone by the Midluteal Phase Corpus Luteum: Temporal Link to Luteinizing Hormone Pulses^*

W. G. ROSSMANITH, G. A. LAUGHLIN, J. F. MORTOLA, M. L. JOHNSON, J. D. VELDHUIS and S. S. C. YEN

Department of Reproductive Medicine, University of California School of Medicine (T-002), and the General Clinical Research Center, University of California-San Diego La Jolla, California 92093
the Division of Endocrinology and Interdisciplinary Graduate Biophysics Program, Departments of Internal Medicine and Pharmacology, University of Virginia School of Medicine Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Dr. Samuel S. C. Yen, Department of Reproductive Medicine, University of California-San Diego School of Medicine, La Jolla, California 92093.

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hormones, we have examined the coincidence of pulses of estradiol (E₂), progesterone (P₄), and LH determined in blood withdrawn at 15-min sampling intervals for a duration of 24 h in each of 15 women during the midluteal phase of the human menstrual cycle.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.

^* This work was supported by NIH Grant HD–12303–11 (to S.S.C.Y.), NIH Research Career Development Award 1-K04-HD-00634 (to J.D.V.), NIH Grants GM-28928 and DK-38942 (to M.L.J.), in part by the General Clinical Research Center, University of California-San Diego, Grants M01-RR-00827 and RR-00847 (to University of Virginia), and DERC 5P60-AM-22125 (to University of Virginia). This research was conducted in part by the Clayton Foundation for Research, California Division.

Fellow, recipient of a German Research Foundation Grant Ro-657/1–2. Present address: Department of Obstetrics-Gynecology, University of Ulm, Prittwitzstrasse 43, D-7900 Ulm/D., West Germany.

Andrew Mellon Foundation Faculty Scholar.

Clayton Foundation Investigator.

Received July 6, 1989.

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