title: Effects of ethane dimethane sulphonate and orchidectomy on luteinizing hormone secretion.
abstract: Abstract The aim of this study was to determine whether testicular products of non-Leydig cell origin modulate rat luteinizing hormone (LH) secretion in vivo. We therefore compared the effects of ethane dimethane sulphonate (EDS), a toxin regarded as highly selective for Leydig cells, with that of bilateral orchidectomy on LH secretion in mature male Wistar rats. The intention was thereby to compare the effects of selective removal of Leydig cells with that of removing both Leydig cells and seminiferous tubules, respectively. Following a single dose of EDS (75 mg/kg, ip), plasma LH concentrations rose equally with those of castrated rats for the first 3 days. After that time, however, plasma LH concentrations in the EDS-treated rats fell progressively below those of the orchidectomized rats despite the continuing castrate level of circulating testosterone until Day 17. The effects of EDS treatment or orchidectomy on pulsatile LH secretion were then compared after 11 days to castrate levels of testosterone. EDS-treated rats demonstrated reduced LH pulse amplitude, mean plasma LH levels and net LH secretion compared with castrate rats, although LH pulse frequency was unaltered. However, a further group of rats treated with EDS and orchidectomized failed to demonstrate that these changes were fully reversed by the castration and therefore EDS may have direct effects upon pituitary LH secretion. In order to determine the mechanism of the reduced LH pulse amplitude after EDS treatment, a further study was conducted to determine whether EDS treatment resulted in reduced pituitary sensitivity to gonadotropin-releasing hormone (GnRH). Responsiveness of pituitary LH to exogenous GnRH (0.01 to 10 mug/kg body wt) was studied 11 days after removal of testicular testosterone feedback by either EDS or castration. Plasma LH response was linearly related to the log of the GnRH dose. At 10 min after GnRH administration, the plasma LH response in EDS-treated rats was less sensitive than in castrate rats. We conclude that the lesser augmentation of LH secretion between Days 3 and 17 after EDS treatment compared with castrate rats cannot be explained solely by changes in Leydig cell secretion but may involve direct effects of EDS on pituitary LH secretion or non-Leydig cell testicular products. Dampening of LH pulse amplitude without change in LH pulse frequency together with the reduced sensitivity to GnRH in EDS-treated rats suggests that this toxin may have direct effects on pituitary LH secretion independent of its effects on Leydig cell function.
authors.affiliation: Departments of Obstetrics and Gynecology and Medicine, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Q
authors.initials: Q
authors.lastname: Dong
authors.forename: D J
authors.initials: DJ
authors.lastname: Handelsman