Desensitization to Gonadotropin-Releasing Hormone in Perifused Chicken Anterior Pituitary Cells*

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Abstract
A perifusion method consisting of dispersed chicken anterior pituitary cells suspended in columns of Bio-Gel was developed to monitor the dynamics of LH release. The perifused cells responded to chicken I GnRH (Gln8-GnRH) in a dose-dependent manner. The ED50 was 3 .times. 10-10 M, and maximal LH release occurred in response to 4 .times. 10-9 M Gln8-GnRH. Continuous administration of 10-7 M Gln8-GnRH and agonist stimulated an initial 8- to 10-fold increase in LH release without minutes. LH release then declined rapidly, reaching basal levels within 100 min. A biphasic response was noted. Calcium ionophore A23187 was effective in releaing additional LH from cells desensitized to 10-7 M Gln8-GnRH and agonist, indicating that total cellular L was not depleted. In contrast, delivery of 2-min pulses of 10-7 and 10-9 M Gln8-GnRH at a frequency of one pulse every 30 or 60 min for 3-5 h maintained pituitary responsiveness. Exposure to 10-7 M Gln8-GnRH for 20 min was sufficient to desensitize pituitary cells to subsequent Gln8-GnRH stimulation. However, 20-min exposure to 10-7 M GnRH antagonist neither evoked LH release nor had a desensitizing effect on subsequent stimulation by 10-7 M Gln8-GnRH, indicating that receptor activation, not merely receptor binding, is necessary for Gln8-GnRH-mediated homologous desensitization. Pituitary cells desensitized by 20-min exposure to 10-8 M Gln8-GnRH maintained responsiveness to a higher dose (10-6 M) of Gln8-GnRH, suggesting that down-regulation of pituitary GnRH receptors might play a part in desensitization. Calcium ionphore A23187 partially desensitized pituitary cells to subsequent stimulation with Gln8-GnRH, probably due to depletion of releasable LH or desensitization of calcium-coupled secretory mechanisms. In calcium-free medium, 10-7 M Gln8-GnRH did not evoke LH release, but nevertheless partially desensitized cells to subsequently 10-7 M Gln8-GnRH stimulation. Thus desensitization is partally calcium-dependent. These findings demonstrate that the phenomenon GnRH-mediated desensitization of gonadotrophs is a characteristic of chicken pituitary cells as in the mammal. However, chicken pituitary cells differ from mammalian cells in that desensitization is more rapid and partially dependent on extracellular calcium.

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