Knobil, E. (1990). The GnRH pulse generator. American Journal of Obstetrics and Gynecology, 163(5 Pt 2), 1721-1727. https://doi.org/10.1016/0002-9378(90)91435-f
Knobil E. The GnRH pulse generator. Am J Obstet Gynecol. 1990;163(5 Pt 2):1721-1727. doi:10.1016/0002-9378(90)91435-f
Knobil, Ernst. "The GnRH pulse generator." American Journal of Obstetrics and Gynecology, vol. 163, no. 5 Pt 2, 1990, pp. 1721-1727.
Each LH pulse follows a burst of GnRH from the brain, a review reports
A 1990 review by Knobil reports that each pulse of luteinizing hormone (LH) from the pituitary gland follows a burst of gonadotropin-releasing hormone (GnRH). Blood LH in ovariectomized monkeys rose and fell about once an hour.
Key Findings
Frequent blood sampling at 10 to 20 minute intervals showed that plasma LH in ovariectomized monkeys fluctuated abruptly and rhythmically, with a period of about one hour.
Earlier reports of seemingly random, major swings in gonadotropin levels in gonadectomized monkeys and rats, and in women, relied on sampling intervals of one hour or longer.
Simultaneous measurements of GnRH in the pituitary portal circulation and LH in peripheral blood rose together, which upheld the view that each LH pulse follows a bolus of GnRH.
Pulsatile secretion of gonadotropic hormones was rapidly extended to most vertebrate species studied, including humans.
Interpretation
The record holds the published abstract of a 1990 review article, so this synopsis reports what the abstract states. The review traces the signal generator idea to blood sampling in monkeys. It also reports that explanations based on feedback from circulating LH had been set aside in recent years.
RRM Context
Restorative reproductive medicine treats the reproductive hormone axis as a timed system. Pulsatile GnRH signaling from the brain underlies the hormone patterns of the menstrual cycle. Cause-based evaluation therefore reads hormone results as part of a rhythm across the cycle.
Our editorial summary of this paper, not the article's abstract.
Abstract
The notion of an oscillator or signal generator in the central nervous system that controls the rhythmic release of GnRH and, thereby, the pulsatile secretion of the gonadotropic hormones, originated in the finding of strikingly abrupt and rhythmic fluctuations in the concentration of LH in the plasma of ovariectomized monkeys. These oscillations had a period of about one hour when blood samples were obtained at 10 to 20 minute intervals.I These surprising observations were presaged by reports of seemingly random, major fluctuations in plasma gonadotropin concentrations in gonadectomized monkeys" and rats as well as in women.' In these earlier studies, the sampling intervals employed were never less than one hour and unable, therefore, to reveal the orderly, rhythmic events that occur with frequencies of one event per hour or more. In the original study describing pulsatile LH secretion in ovariectomized monkeys the possibility was considered that the circhoral discharges of LH may be initiated by autoregulatory mechanisms involving long or short feedback loops, but the more likely view that these discharges were due to intermittent signals from the central nervous system unrelated to circulating LH levels that resulted in putative increments in GnRH release was favored. Nevertheless, the possible role of autoregulatory mechanisms in the control of pulsatile LH secretion was repeatedly considered,6 but finally laid to rest in the relatively recent past.7Conversely, the view that each pulse of LH released from the pituitary gland is the consequence of a bolus of GnRH secreted into the pituitary portal system has been unequivocally upheld by the demonstration of synchronous increments of GnRH assessed in the pituitary portal circulation and of LH measured in samples of peripheral blood obtained simultaneously.s, 9 In any case, the phenomenon of pulsatile gonadotropic hormone secretion was rapidly extended to most vertebrate species studied in this regard, including our own, and forms the basis of an increasingly voluminous, rapidly expanding literature.
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