FUNCTIONAL ASSESSMENT OF INTRAHYPOTHALAMIC IMPLANTS OF IMMORTALIZED GONADOTROPIN-RELEASING HORMONE-SECRETING CELLS IN FEMALE HYPOGONADAL MICE

The hypogonadal (HPG) mouse is a mutant that lacks a functional gonado tropin-releasing hormone (GnRH) gene. In this study, female HPG mice r eceived bilateral intrahypothalamic implants of an immortalized GnRH-s ecreting cell line (GT1-7). Nine mice were tested 4265 days after impl antation to determine whether these cells could support spontaneous an d/or N-methyl-D,L-aspartic acid (NMDA)-stimulated luteinizing hormone (LH) secretion. When sampled via intravenous catheters, four mice had measurable LH secretion. Three of these mice responded to NMDA challen ges with significant increases in circulating LH. GnRH immunocytochemi stry revealed that GT1-7 cells were present in these four mice and thr ee others in which LH values were not detectable. There were about 120 0 GnRH cells dispersed within the piriform cortex and olfactory tuberc le, and no tumor found in one of the HPG mice that responded to NMDA, whereas the other NMDA responders had large bilateral hypothalamic tum ors. The presence or absence of such tumors did not predict the capaci ty to respond to the NMDA challenge with alterations in LH secretion. This study provides the first evidence that intrahypothalamic GT1-7 ce lls can support LH release in the HPG mouse, and that this secretion c an be modified by pharmacological agents.