Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion

Abstract

The pattern of episodic gonadotropin release was studied in 15 normal female volunteers during the luteal phase of the menstrual cycle with 24 h of blood sampling for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at 10-min intervals. Six subjects (two in the early, two in the mid-, and two in the late luteal phase) also had each of these specimens processed for progesterone levels. A progressive slowing of LH pulsations were present across the luteal phase with the mean LH pulse frequency declining from 15.2 pulses/24 h in the early to 8.4/24 h in the late luteal phase. A trend towards reduction in the amplitude of LH pulses was also observed (12.3 ± 2.2 SD mIU/ml in the early vs. 8.6 ± 3.4 mIU/ml in the late luteal phase; NS). In addition, LH pulses of heterogeneous amplitude were identified during the same 24-h study. The mean ±SD of the larger and of the smaller LH pulses was 16.9 ± 4.7 and 2.3 ± 1.0 mIU/ml, respectively (P < 0.001). While the slowing of the frequency of all LH pulses correlated well (r = 0.80, P < 0.001) with the day of the luteal phase and poorly with the actual plasma progesterone levels, the incidence of the small LH pulses was highest in the mid-luteal phase and correlated well with the mean progesterone plasma levels ( r = 0.63, P < 0.01). In the early luteal phase, the pattern of progesterone secretion was stable over the 24-h studies and showed no relationship to episodic LH release. In contrast, in the mid- and late luteal phase, plasma progesterone concentrations rapidly fluctuated during the 24-h studies from levels as low as 2.3 to peaks of 40.1 ng/ml, often within the course of minutes. Progesterone increments closely attended episodes of LH release, as documented by the significant (P < 0.05) cross-correlation between LH and progesterone levels, at time lags of 25-55 min. The results of this study indicate that in the human luteal phase: (a) the frequency of pulsatile release of LH declines progressively and correlates well with the duration of exposure to progesterone; (b) the amplitude of LH pulses varies with the appearance of an increased percentage of smaller pulses correlating well with the acute level of progesterone; (c) in the early luteal phase, the pattern of progesterone secretion is stable; (d) in the mid- and late luteal phase, progesterone secretion is episodic, and correlates well with LH pulsatile release; and (e) single progesterone estimations in the mid- and late luteal phase do not accurately reflect corpus luteum adequacy.