Dynamic Characteristics of Luteinizing Hormone Release from Perifused Sheep Anterior Pituitary Cells Stimulated by Combined Pulsatile and Continuous Gonadotropin-Releasing Hormone*

We aim to quantify and relate the dominant dynamic factors of GnRH signals and of the resultant patterns of LH release from pituitary cells. Using perifused sheep cells we have already shown that rising edges of GnRH pulses are major effectors of LH release and that a longer absence of signal between pulses improves response. This study reports the effects on LH release dynamics of continuous levels of GnRH with superimposed pulses and of slowing the important rising edge of the GnRH pulses. Low baseline GnRH perifusions at physiological levels (5-60 pM) reduced the response to hourly pulses of 850 pM GnRH. Continuous GnRH (420 pM), which initially yielded maximal LH release followed by desensitization, prevented extra stimulation by pulses of equal concentration, but 10-fold higher pulses gave additional LH output. After desensitization an hour's respite from stimulation resensitized cells to 420 pM pulses. Whereas continuous stimulation of cells with GnRH even at the very low level of 5-10 pM [ED50 = 58 +/- 6 (SE) pM] produced desensitization in 10-15 min, slowly rising GnRH (0.56-14 pM/min) caused increasing LH output with time. However, in comparison with square wave pulses, stimulatory signals consisting of slowly rising concentrations of GnRH produced peaks characterized by less total LH output and a changed shape. This was consistent with desensitization at low concentrations of GnRH reducing response to later increases in the level of stimulation. The mechanism for detecting GnRH signals and/or the mechanisms controlling release of LH were desensitized to constant GnRH at any concentration but retained a reduced sensitivity, or developed an additional release capacity, to increased levels of GnRH. Properties of four distinct types of LH release dynamics were described quantitatively and were shown to be controlled by different time constants in the GnRH pulse stimulation patterns.