GONADAL STEROIDS ARE CAPABLE OF ACTING WITHIN THE HYPOTHAIAMUS TO MODULATE SOMATOSTATIN (SS) GENE EXPRESSION IN PUBERTAL AGED RATS

Abstract

Due to the highly complex nature of neuroendocrine-target organ “feedback” relationships, the primary site(s) at which gonadal steroids exert effects on the GH axis remain largely unknown. Therefore, we sought to test the hypotheses that testosterone (T) and estrudiol (E2) can exert direct cell-specific regulatory effects in vivo on hypothalamic neurons which control GH secretion. 7 male rats were castrated at 25d (prepubertally). On day 40, T or E2 was stereotaxically placed into the hypothalamus lateral to the periventricular nucleus (PeN) at the level of the paraventricular n. (PvN). Vehicle (cholesterol) was placed at the identical conicalateral location. Preliminary studies using peroxidase-conjugated E2 demonstrated no crossover of test steroid to the control side. This model allowed exposure of only one side of the hypothalamus to a change in gonadal steroid milieu during a developmental period within which the systemic rise in gonadal steroios occurs naturally in vivo. Using in situ hybridization, we then compared the level ofSS gene expression in PeN neurons of the treatment (TX) vs control (CON) sides. In all 7 brains, the level of SS gene expression was lower (p<.05) in neurons of the TX vs. CON side (86.7±0.3% of CON for T and 80.4 ± 3.6% for E2). Furthermore, the TX effect was anatomically discrete with the dominant effect in the mid PeN region (level of the PvN) and either absent or minor toward the rostral-caudal extremes. These data demonstrate direct in vivo intrahypothalamic regulatory effects of T and E2 on one neuronal subpopulation critical tor control of pituitary GH secretion. This finding strongly indicates that at least one important site for the modulatory effects of T and E2 on the GH axis is within the hypothalamus. This technical approach of highly localized delivery of putative regulatory substances followed by subsequent assessment of gene expression within discrete neuronal subpopulations carries great potential to provide insight toward answering numerous remaining questions regarding neuroendocrine control of GH and other hypothalamic pituitary hormone systems.