Definitive evidence for the existence of morphological plasticity in the external zone of the median eminence during the rat estrous cycle: implication of neuro-glio-endothelial interactions in gonadotropin-releasing hormone release.

Despite intense investigation, the demonstration of morphological plasticity in the external zone of the median eminence concerning the gonadotropin-releasing hormone system has never been reported. In this study, we investigate whether dynamic transformations of the gonadotropin-releasing hormone nerve terminals and/or tanycytes in the external zone of the median eminence of the hypothalamus occurred during the rat estrous cycle, by following individual gonadotropin-releasing hormone-immunoreactive nerve terminals on serial ultrathin sections observed by electron microscopy. Female rats were killed at 16.00 diestrus II (n = 3), i.e. when estrogen levels are basal and gonadotropin-releasing hormone release is low, and at 16.00 proestrus (n = 4), i.e. when estrogen levels peak and the preovulatory gonadotropin-releasing hormone surge occurs. Our results show that, in the median eminence obtained from proestrus rats, 12+/-2% of the gonadotropin-releasing hormone nerve terminals were observed to make physical contact with the parenchymatous basal lamina, i.e. the pericapillary space. In the median eminence obtained from diestrus II rats, no contacts were observed. On proestrus, numerous physical contacts between gonadotropin-releasing hormone nerve terminals and the basal lamina occurred by evagination of the basal lamina and/or by emerging processes from gonadotropin-releasing hormone nerve terminals. The quantification of the evagination of the basal lamina revealed that the basal lamina was at least twofold more tortuous in appearance during proestrus. These results demonstrate for the first time the existence of dynamic plastic changes in the external zone of the median eminence, allowing gonadotropin-releasing hormone nerve terminals to contact the pericapillary space on the day of proestrus, thus facilitating the release of the neurohormone into the pituitary portal blood.