Effects of congenital hydrocephalus on the hypothalamic gonadotrophin-releasing hormone system

Abstract

Object Despite the investigations that have linked hydrocephalus to reproductive system abnormalities, no researchers have attempted to identify the pathophysiological mechanism of this relationship. Because the role of the hypothalamic gonadotrophin-releasing hormone (GnRH) system in the regulation of reproductive functions is well established, the authors used immunohistochemical and radioimmunoassay (RIA) techniques to determine the morphological and biochemical effects of hydrocephalus on the hypothalamic GnRH system. Methods Hypothalamic GnRH levels, fiber density, and cell types were studied in 21- and 50-day-old control and congenitally hydrocephalic Texas rats. Results of RIA indicated a significant (8.4%) increase in GnRH in 21-day-old hydrocephalic rats (9.17 ± 0.64 pg/ng total protein) compared with that in controls (0.97 ± 0.74 pg/ng total protein). In addition, the 50-day-old hydrocephalic animals had a significantly higher level of GnRH compared with age-matched controls (20.4 pg/ng compared with 1.88 ± 2.1 pg/ng total protein). This increase was accompanied by changes in the fiber appearance and a shift from low GnRH producing cells to high GnRH producing cells in the hydrocephalic animals; however, there was no significant difference in the fiber density between the control and hydrocephalic animals at 21 days. In addition, poor neurological scores correlated with the severity of hydrocephalus. Conclusions These results demonstrated that hypothalamic GnRH levels are significantly affected by fetal-onset hydrocephalus and that the mechanisms responsible for these effects may take place at the cellular rather than the gross structural level. Furthermore, they suggest that impairments in the GnRH system may be protracted in neonates and infants with hydrocephalus, and thus may be overcome by relatively early treatment with ventricular diversion. However, the clinical implications of GnRH perturbations in shunt-dependent patients must await a forthcoming study in shunted animals.