Disruption of testosterone homeostasis as a mode of action for the reproductive toxicity of triazole fungicides in the male rat.
We have previously reported that in castrated male rats gonadal steroids can raise LHRH levels in the medial basal hypothalamus (MBH). However, there was an important dissociation between episodic LH release and the MBH LHRH response to 17 beta-estradiol. In the present study we have examined the effects of varying the dose of testosterone (T) on the MBH LHRH levels, episodic LH release pattern, and pituitary responsiveness to LHRH; in addition we have determined the duration of T exposure required to elicit the MBH LHRH response. Results show that low serum levels of T (413-638 pg/ml) were just as effective as higher concentrations (1337-1776 pg/ml) in raising the MBH LHRH levels at 96 h; the minimum duration of exposure to T was 72 h. However, whereas higher T levels (greater than 1 ng/ml) suppressed LH release coincident with elevated LHRH levels, low T concentrations did not alter LH release contemporaneous with the MBH LHRH elevations. Analysis of the episodic LH secretion pattern disclosed that these low concentrations of T changed neither the number of pulses per 3 h per rat, pulse amplitude, nor the interpulse interval. On the other hand, as T concentrations were increased, pulse amplitude fell in a dose-related manner while other components of episodic LH secretion remained unchanged. Despite these differential effects of T on the LH release pattern, pituitary sensitivity to exogenous LHRH was reduced by the low as well as high levels of T. These studies show that 1) T can activate those intracellular neurosecretory events that are involved in augmented LHRH supply to the nerve terminals in the median eminence; 2) T can stimulate LHRH accumulation in the MBH by mechanisms that may not involve inhibition of LHRH release; and 3) higher T levels do not alter LH pulse frequency but depress only the pulse amplitude that may result from decrements in the amounts of LHRH released with each neural episode and depressed pituitary sensitivity to LHRH.