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Increased Pulsatile, But Not Basal, Growth Hormone Secretion Rates and Plasma Insulin-Like Growth Factor I Levels during the Periovulatory Interval in Normal Women

Department of Gynecology and Obstetrics, Skejby Sygehus (P.O.); Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital (N.V., J.S.C., J.O.L.J.); and Institute of Experimental Clinical Research, Aarhus University (S.F.), Aarhus, Denmark; and the Endocrinology Division (J.D.V.), National Science Foundation Center for Biological Timing, and University of Virginia Health Sciences Center, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Per Ovesen, M.D., Department of Gynecology and Obstetrics, Skejby Sygehus, DK-8200 Aarhus N, Denmark.

The secretion of GH changes during the menstrual cycle, exhibiting high levels during the periovulatory phase (PO). Previous studies have not investigated whether this difference in GH status is due to increased secretion or reduced clearance of pituitary GH and amplified pulsatile vs. basal GH secretion. It is also unclear whether the PO phase is accompanied by changes in circulating insulin-like growth factor I (IGF-I). In this study we investigated the 24-h GH release patterns in the early follicular (EF) vs. the periovulatory menstrual phase in the same individuals. Ten young (aged 24–34 yr) healthy women with regular menses were studied with deconvolution analysis of GH profiles obtained by blood sampling every 20 min for 24 h, followed by an arginine stimulation test. A high sensitivity immunofluorometric GH assay was used. All women were studied in both the EF and PO phases in random order. There were no differences in the basal GH secretion rate or GH half-life during the two phases. The number of GH secretory bursts identified during the 24-h sampling period was significantly increased during the PO (13.3 ± 0.5) compared to the EF (10.3 ± 0.6) phase (P = 0.002); conversely, the mean interburst interval was shorter in the PO (107 ± 5 min) than in the EF (134 ± 8 min) phase (P = 0.004). There was no difference in GH pulse mass (P = 0.13) or amplitude (P = 0.21) between the two phases. The pulsatile GH production rate (milligrams per L/24 h) was significantly elevated during the PO (61 ± 6) compared to that during the EF (37 ± 8; P = 0.004). Increased total GH pulse area was confirmed by Cluster analysis (P = 0.027). Furthermore, the 24-h mean serum GH concentration was significantly increased in the PO (1.4 ± 0.1 mg/L) vs. that in the EF (0.9 ± 0.1 mg/L; P = 0.002). There was a positive correlation between estradiol (E₂) and GH secretory pulse amplitude, frequency, and mean 24-h serum GH concentration in the PO cycle phase, indicating E₂ to be a major statistical determinant of GH secretion. Serum GH increased significantly after arginine infusion in both phases (P < 0.001), whereas there was no difference between the two cycle phases (P = 0.20). Serum IGF-I levels were increased during the PO phase (253 ± 20 mg/L) compared to those during the EF phase (210 ± 16 mg/L; P = 0.03), whereas serum IGF-binding protein-3, IGF-II, and GH-binding protein were similar during the two phases. This study unequivocally documents elevated GH levels during the PO phase of the menstrual cycle, mediated by increased GH production rate and burst frequency. The concomitant increase in serum IGF-I suggests a central stimulation of the GH-IGF-I axis, which may be mediated by endogenous E₂ levels.

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