An evaluation of the inhibition of androgenization of the neonatal female rat brain by barbiturate.

Abstract

Simultaneous subcutaneous (s.c.) injection of pentobarbital (PB) and testosterone propionate (TP) has been reported to inhibit neonatal androgenization. In an attempt to elucidate the level of this interaction, PB was infused bilaterally into the anterior hypothalamus of 2- and 5-day-old female rats that were also given TP s.c.; neonatal female rats were injected s.c. with PB daily for 3 or 4 days prior to the s.c. injection of TP. The fact that steroids can act in the region of the hypothalamus exposed to PB infusion was established by demonstrating that anovulatory sterility was produced by the intrahypothalamic infusion at similar coordinates of either TP or estradiol benzoate at doses (2 and 1 <i>µ</i>g, respectively) inactive s.c. Nevertheless, PB infusion into this region did not consistently inhibit s.c. TP. In contrast, repetitive treatment of the neonatal rat with TP s.c. for 4 days was able to inhibit androgenization, which suggests that PB can act peripherally, probably at the level of the liver. However, prolonged exposure to PB is critical, since treatment for only 3 days was unable to prevent the action of exogenous TP. The latter results indicate that the effectiveness of single s.c. injection of PB cannot be attributed to the stimulation of liver function. It is concluded that the lack of effectiveness of intrahypothalamic PB against androgenization may be related to differences in the site(s) of action of TP and PB or to the temporal characteristics of their action, rather than providing evidence that the interaction between PB and TP is peripheral. The control animals for the above experiments, which were obtained from a commercial source, developed an unexpectedly low incidence of sterility (IS) compared to previous results obtained in this laboratory with a local colony of animals. The effectiveness of s.c. PB against the action of TP was re-evaluated in these animals of differing sensitivity to androgen. The fact that s.c. PB can inhibit androgenization was