Characterization of the Physiological Pattern of Episodic Gonadotropin Secretion throughout the Human Menstrual Cycle*

Abstract

To characterize the spectrum of pulsatile gonadotropin secretion during the course of the normal menstrual cycle, we studied normal women during 51 ovulatory cycles. Plasma gonadotropin concentrations were measured at 10-min intervals for 20-24 h during the early, mid-, and late follicular phases and the early, mid-, and late luteal phases. LH data series were analyzed using 2 different computer-assisted algorithms for pulse detection. The LH interpulse interval decreased during the follicular phase (FP) from 94 +/- 4 (+/- SEM) min in the early FP (EFP) to 71 +/- 4 min by the late FP (LFP; P less than 0.001). The estimation of LH pulse frequency in the EFP was significantly affected by slowing of episodic LH secretion during sleep. In the luteal phase (LP), the LH interpulse interval progressively increased from 103 +/- 8 min in the early LP (ELP) to 216 +/- 39 min by the late LP (LLP; P less than 0.001). Sleep-associated slowing of episodic LH secretion also occurred in the ELP. The mean LH pulse amplitude in the EFP (6.5 +/- 0.4 mIU/ml) decreased significantly by the midfollicular phase (MFP; 5.1 +/- 0.8 mIU/ml; P less than 0.05) and increased once again by the LFP (7.2 +/- 1.2 mIU/ml). LH pulse amplitude was highest in the ELP (14.9 +/- 1.7 mIU/ml), decreased by the midluteal phase (MLP) to 12.2 +/- 2.0 mIU/ml, and declined further by the LLP to 7.6 +/- 1.1 mIU/ml (P less than 0.001 vs. ELP). FSH secretion was significantly (P less than 0.05) correlated with LH secretion at time lags of 0-10 min in 82% of the studies. These results indicate the following. 1) In the EFP and ELP, the frequency of gonadotropin pulsations is reduced at night in association with sleep. 2) The frequency of LH secretion increases from the EFP to MFP and LFP. 3) LH pulse amplitude decreases in the MFP, suggesting enhanced negative feedback of estrogen on the hypothalamic-pituitary axis and/or a decrease in GnRH secretion at this stage. 4) A progressive reduction of LH pulse frequency and amplitude occurs during the LP which is correlated with the duration of exposure of the hypothalamic-pituitary axis to progesterone. 5) A close relationship exists between secretion of LH and FSH, suggesting a common stimulatory factor for both gonadotropins.

Kisspeptin mRNA expression is increased in the posterior hypothalamus in the rat model of polycystic ovary syndrome

“…On the other hand, in humans who have a longer cycle than rodents, the LH pulse frequency is the shortest in the mid and late follicular phase (around 70 min) when the estrogen level is high, while it is longer in the early follicular phase (90-100 min) and in the luteal phase (120-200 min) [36]. The tone or strength of the estrogen negative feedback on gonadotropin secretion appears to be transient according to follicular development in humans [37]; the tone of the negative feedback to the hypothalamus is weaker in the late follicular phase than in the early follicular phase.…”

G Protein-Coupled Receptor Trafficking in Health and Disease: Lessons Learned to Prepare for Therapeutic Mutant Rescue in Vivo

“…The GnRHR itself cycles in rodents and primates (Filicori et al, 1986), and there is the possibility that this process could be neatly controlled by endogenous chaperones (Brothers et al, 2006). To set the stage for in vivo studies, we have examined the molecular aspect of the WT primate GnRHR that might cause this molecule to be amenable to regulation by pharmacoperones.…”

Decreased release of gonadotropin-releasing hormone during the preovulatory midcycle luteinizing hormone surge in normal women.

“…Additional studies were performed at a dose of 5 pg/kg in the early follicular phase (5 or 6 women studied at each dose), at all four doses in the late follicular phase (6-11 women studied at each dose) and the midcycle surge (3-6 women studied at each dose), and at the three highest doses in the early luteal phase (4 or 5 women studied at each dose). Cycle phases were determined prospectively by previous menstrual cycle history, transvaginal ultrasound examination, and basal body temperature charts and confirmed retrospectively by comparison of hormonal characteristics on the day of the study with the previously published series of 64 normal women studied in this laboratory (17). Women studied in the early follicular phase were admitted between days 2 and 5 from the onset of menses, and those in the late follicular phase group were studied >9 days from the onset of menses and had a mean baseline LH value within 2 SEMs of late-follicular-phase LH values (17).…”

“…Cycle phases were determined prospectively by previous menstrual cycle history, transvaginal ultrasound examination, and basal body temperature charts and confirmed retrospectively by comparison of hormonal characteristics on the day of the study with the previously published series of 64 normal women studied in this laboratory (17). Women studied in the early follicular phase were admitted between days 2 and 5 from the onset of menses, and those in the late follicular phase group were studied >9 days from the onset of menses and had a mean baseline LH value within 2 SEMs of late-follicular-phase LH values (17). In the midcycle surge group, the baseline LH was >2 SEMs above the late-follicular-phase values and progesterone (P) was <6 nmol/liter.…”