Pituitary gland responsiveness to LHRH and LHRH neuronal responsiveness to excitatory stimuli are severely impaired in female rats treated neonatally with high doses of androgen

Abstract

Treatment of neonatal female rats with androgen renders these animals permanently sterile as adults. Previously, we reported that these androgen-sterilized rats (ASR) do not respond to the positive feedback effects of estrogen by having LH surges. We also reported that this defect might be due to the failure of these animals to show increased hypothalamic norepinephrine turnovers (an index of secretion) in response to steroid treatment. Although LHRH-catecholamine synapses are established before or at birth, whether such synapses are functions remains to be resolved. Accordingly, the present studies, female rats were ggiven 1.25 mg of testosterone propionate at 5 days of age and, at 100 days of age, these ASR and controls were ovariectomized and treated with estradiol. In these animals, we examined whether activation of medullary A1 noradrenergic neurons would amplify LH release following preliminary depolarization of LHRH neurons with an electrochemical stimulus (ECS). As well, we reexamined whether LHRH neuronal responsiveness to exogenous NE and pituitary responsiveness to LHRH differ in controls versus ASR. In controls, two pulses of LHRH given 60 min apart elicited increases in plasma LH with the second pulse inducing greater LH release than the first pulse. In ASR, significantly less LH was released after either LHRH pulse and particularly after the second pulse. When the spacing between the two LHRH pulses was reduced to 25 min, equivalent levels of LH release occured in controls and ASR after the second pulse. The i.c.v. infusion of NE induced a rapid rise in plasma LH in both controls and ASR although the peak LH responses (at 10 min) were significantly less in the ASR group. When the medial preoptic area (MPOA) was ECS, plasma LH increased in both groups of rats but significantly less LHRH was released in ASR. Combined MPOA-ECS+i.c.v. NE in controls and ASR resulted in amplification of LH release above that obtained after only MPOA-ECS. However, the amount of LH released in ASR was significantly less than controls. In the final study, bilateral MPOA-ECS was performed and 20 min later the right A1 cell group was electrically stimulated (ES) for 15 min. In control rats, combined MPOA-ECS+A1-ES resulted in greater LH release than occured after MPOA-ECS alone. Although similar combined preoptic+A1 stimulation also amplified LH release in ASR, the plasma LH concentrations were significantly less than controls. From these studies we conclude that: (1) pituitary responsiveness to LHRH is less in ASR than controls; (2) LHRH neuronal responsiveness to various excitatory stimuli also is less in ASR compared to controls; (3) the responses of LHRH neurons to Ai-ES in controls and ASR indicate that endogenous NE signals evoke LHRH release.