HYPOTHALAMIC NEUROPEPTIDE-Y GENE-EXPRESSION INCREASES BEFORE THE ONSET OF THE OVARIAN STEROID-INDUCED LUTEINIZING-HORMONE SURGE

Neuropeptide-Y (NPY), a hypothalamic peptide, is involved in stimulati on of LHRH and LH surges during proestrus and those induced by ovarian steroids in ovariectomized (ovx) rats. The NPY neurons that reside in the arcuate nucleus of the medial basal hypothalamus (MBH) and accumu late 17 beta-estradiol participate in the initiation of LHRH and LH su rges. To determine whether NPY synthesis is altered in conjunction wit h the LH surge, we studied the dynamic changes in prepro-NPY mRNA leve ls in the MBH in association with the LH surge elicited by estradiol b enzoate (EB) alone or by progesterone (P) in EB-primed ovx rats. Five days after ovariectomy, rats received oil or EB (30 mu g/rat) at 1000 h on day 0. On day 2, these rats were injected with either oil or P (2 mg/rat) at 1000 h. Rats were killed before (1000 h) and at 2-h interv als after oil or P injection. The MBHs were dissected out and processe d for determination of prepro-NPY mRNA levels by solution hybridizatio n/RNase protection assay using a cRNA probe. Although in control ovx r ats, prepro-NPY mRNA levels remained unchanged between 1000-1600 h, pr epro-NPY mRNA levels showed dynamic changes in steroid-primed rats. In the EB-primed rats, prepro-NPY mRNA levels rose significantly (100%) at 1200 and 1400 h before the LH rise at 1600 h, and the levels remain ed elevated up to 1800 h. After P injection to the EB-primed rats, thi s response was further augmented, with a slightly different temporal p attern. Prepro-NPY mRNA levels rose at 1400 h (600%) before the onset of the LH rise at 1600 h and declined steadily to significantly lower values at 1800 h, coincident with the highest rate of LH secretion. Th ese studies demonstrate dynamic shifts in hypothalamic NPY gene expres sion in association with the LH (LHRH) surge, and that maximal increas es occur before the onset of the LH rise, but thereafter, NPY gene exp ression diverged in the two ovarian-steroid treatment models. These fi ndings along with previous evidence of similar antecedent increases in NPY content in the median eminence, followed by release, suggest that augmented NPY synthesis and release are two temporally dissociable ne ural events for the LHRH and LH surges.