Frequency and Amplitude of Gonadotropin-Releasing Hormone Stimulation and Gonadotropin Secretion in the Rhesus Monkey*

Abstract

In adult ovariectomized rhesus monkeys bearing hypothalamic lesions which reduced circulating LH and FSH to undetectable levels, sustained elevated gonadotropin concentrations were reestablished by the intermittent administration of gonadotropin-releasing hormone (GnRH) at the rate of 1 microgram/min for 6 min once every hour. The effects of varying either the frequency or the amplitude of these GnRH pulses on gonadotropin secretion were examined in such animals. Increasing the frequency of GnRH administration from the physiological one pulse per h to two, three, or five pulses h while maintaining a constant infusion rate and pulse duration resulted in gradual declines in plasma gonadotropin concentrations. These declines were most profound at the highest frequencies and the consequence of reduced pituitary responses to individual GnRH pulses. Decreasing the frequency of GnRH pulses from one per h to one every 3 h led to variable declines in plasma LH levels, but circulating FSH invariably rose. Reducing the GnRH infusion rate from 1 to 0.1 mg/min while maintaining constant frequency and pulse duration resulted in abrupt declines in plasma LH and FSH to immeasurable levels, although pulsatile increments in circulating GnRH concentrations without a concomitant reduction in plasma LH concentrations, which remained unchanged. An infusion rate of 0.5 microgram/min resulted in unstable plasma LH and FSH levels. These results demonstrate that changes in the frequency or amplitude of hypophysiotropic stimulation have profound effects on plasma gonadotropin levels as well as on FSH to LH ratios in the circulation. The physiological implications of these observations are discussed.

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

“…Other receptors also may have the ability to transduce a complex signal that is both amplitudeand frequency-modulated and, in the case of the GnRHR, alterations in pulse frequency may provide a means of therapeutic intervention. Because an increased level of FSH over several days seems to be needed to recruit a dominant follicle for ovulation (Wildt et al, 1981), accurate sensing of pulses is important for ovulation. In patients with HH bearing GnRHR mutations, a variable profile of spontaneous pulsatile LH release, from completely apulsatile to decreased frequency and amplitude of pulsatile release, has been found, depending on the particular receptor mutations presented (de Roux et al, 1997(de Roux et al, , 1999Beranova et al, 2001;Layman et al, 2001;Meysing et al, 2004).…”

Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: Implications for a common fertility disorder

“…Steroids feed back to regulate GnRH pulse frequency. Variations in GnRH pulse frequency during the cycle are critical for the differential synthesis and release of LH and FSH; low frequency pulses favor FSH, and high frequencies favor LH (2,3). During the luteal phase, progesterone negative feedback reduces GnRH pulse frequency (4-6), favoring FSH synthesis.…”

5-HT1 and 5-HT2 receptor activation reduces N-methyl-D-aspartate (NMDA)-stimulated LH secretion in prepubertal male and female rats

“…Alternatively, it should be considered that the selective release of both gonadotropins is related to the frequency and amplitude of LHRH pulses. Pituitary stimulation with low-frequency pulses of LHRH selectively stimulates FSH secretion (32,33); it is possible that activation of 5-HT 1A , 5-HT 2 and 5-HT 3 receptors selectively reduced the frequency of LHRH pulses.…”