Effects of the noradrenergic neurotoxin DSP4 on growth and the gonadal steroid-and PMSG-induced release of LH in the prepubertal female rat

Abstract

We have examined the effect of DSP4 treatment on PMSG-induced ovulation. A marked attenuation of the stimulatory effects of PMSG (7.5 I.U.) by DSP4 was evidenced by the significantly lower number of corpora lutea present in the ovaries of those animals which ovulated compared to controls. In addition, ovarian weight was lower in the DSP4 group. In a further experiment, we examined the effect of DSP4 on the induction of an LH surge by progesterone (P) in estradiol benzoate (EB) primed rats. DSP4 administration 2 hours prior to P eliminated the LH surge seen in controls. In view of our previous observations that DSP4 can interact with opioid receptors, we attempted to block its inhibitory effect on PMSG and EB/P stimulations. Coinjection of naloxone, an opioid antagonist, only partially prevented the influence of DSP4. It seems likely, therefore, that opioid receptors are not involved in the inhibitory effects of DSP4 described here. In further experiments, we studied the effects of DSP4 on spontaneous sexual maturation in female rats. DSP4 was administered (50 mg/kg, IP) on either day 5, day 23, day 29, or both day 24 and day 26 of life. Growth was inhibited and vaginal opening (VO) was significantly delayed in all except the day 29 group. However, VO occurred at the same body weight as the controls. By the end of the experiment, hypothalamic noradrenaline levels were not significantly different between control and DSP4-treated animals. The lack of an effect of DSP4 on the progression to puberty may be due to sufficient recovery of the central noradrenergic systems during the time course of the experiments. Our findings that the neurotoxin DSP4 affects both PMSG-induced ovulation and gonadal steroid-induced LH surges points out the potential usefulness of this drug as a probe of the role of the noradrenergic system in sexual maturation.