CHRONOBIOLOGY OF PROLACTIN SECRETION IN WOMEN - DIURNAL AND SLEEP-RELATED VARIATIONS IN THE PITUITARY LACTOTROPH SENSITIVITY

While a nocturnal rise accounts for the marked circadian variability of prolactin (PRL) secretion in humans, the mechanisms subserving this neuroendocrine manifestation are still obscure. Since gonadotropin-releasing hormone (GnRH) stimulates PRL under physiological conditions, we questioned whether changes in the pituitary lactotroph sensitivity to GnRH during the 24-hour cycle may contribute to the expression of circadian PRL rhythmicity. Accordingly, 8 women were studied in the early follicular phase of their cycles (days 2-5) on 6 occasions in random order: during daytime between 10.00 and 14.00 h ('day' studies), at night between 22.00 and 02.00 h, when the women were awake ('night' studies), and finally, during the identical night hours, when the women were asleep ('sleep' studies). On all occasions, blood was collected at 10-min intervals for 4 h, while either GnRH (25 mug i.v. bolus) or saline (as control) was injected twice within 2 h. As assessed by the net PRL increments (differences between unstimulated nadir and stimulated peak) and the areas under the PRL response curves, the PRL secretion was not substantially altered following GnRH stimulations during the day studies. In contrast, PRL release was markedly enhanced (p < 0.05 or less vs. day studies), when GnRH was administered during the night studies. This GnRH-stimulated PRL release was even further increased (p < 0.01 vs. day, p < 0.05 vs. night or saline studies), when GnRH had been given during sleep. In the night studies, the PRL release in response to the second GnRH stimulations was greater (p < 0.05) than in response to the first. Yet, this ratio was clearly reversed during sleep, when initial GnRH challenges provoked much greater (p < 0.05) PRL increments than the following. Thus, diurnal variations in the lactotroph sensitivity to GnRH stimulations are expressed in women, with a greater PRL responsiveness observed at night. Sleep at nocturnal hours may further augment this circadian swing. In addition, the release capacity of the pituitary lactotroph following repetitive GnRH stimulations varies in accordance with the wake-sleep cycle. These combined observations permit us to infer that diurnal and sleep-related variations in the lactotroph sensitivity may, at least in part, contribute to the chronorhythmicity of PRL secretion in women.