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 o f prolactin (PRL) secretion in humans, the mechanisms subserving this neuroendocrine manifestation are still obscure. Since gonadotropin-rel easing hormone (GnRH) stimulates PRL under physiological conditions, w e questioned whether changes in the pituitary lactotroph sensitivity t o GnRH during the 24-hour cycle may contribute to the expression of ci rcadian PRL rhythmicity. Accordingly, 8 women were studied in the earl y 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 n ight between 22.00 and 02.00 h, when the women were awake ('night' stu dies), and finally, during the identical night hours, when the women w ere 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 sa line (as control) was injected twice within 2 h. As assessed by the ne t PRL increments (differences between unstimulated nadir and stimulate d 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 res ponse to the second GnRH stimulations was greater (p < 0.05) than in r esponse to the first. Yet, this ratio was clearly reversed during slee p, when initial GnRH challenges provoked much greater (p < 0.05) PRL i ncrements than the following. Thus, diurnal variations in the lactotro ph sensitivity to GnRH stimulations are expressed in women, with a gre ater PRL responsiveness observed at night. Sleep at nocturnal hours ma y further augment this circadian swing. In addition, the release capac ity of the pituitary lactotroph following repetitive GnRH stimulations varies in accordance with the wake-sleep cycle. These combined observ ations permit us to infer that diurnal and sleep-related variations in the lactotroph sensitivity may, at least in part, contribute to the c hronorhythmicity of PRL secretion in women.