Electrical activity of the pulse generator of gonadotropin-releasing hormone in 26-month-old female rats.

Abstract

To know whether age-related changes occur in the activity of the pulse generator of gonadotropin-releasing hormone (GnRH), old (26 months) and young (3 months) female rats were examined by recording multiunit activity (MUA) in the median eminence region of the hypothalamus, concurrently with blood samplings through an intra-atrial cannula at 6-min intervals to determine serum luteinizing hormone (LH) concentrations. We have regarded the MUA showing intermittent increases (volleys) at 20-30 min intervals, followed by LH pulses, as the electrical activity of the GnRH pulse generator. We were successful in recording MUA in 18 (26%) of 69 old ovariectomized rats and in 8 (32%) of 25 young ovariectomized rats. The overall mean (+/-SE) of the interval between MUA volleys in old ovariectomized rats was 35.1 +/- 2.0 min (n = 18), which was significantly longer than that of 22.5 +/- 1.5 min (n = 8) in young ovariectomized rats. The mean interval between LH pulses in old ovariectomized rats was 32.2 +/- 3.6 (n = 10), also being significantly longer than that of 23.3 +/- 1.0 (n = 8) in young ovariectomized rats. Further, the LH pulse amplitude in old rats (0. 95 +/- 0.07 ng/ml) was significantly smaller than in young rats (3. 40 +/- 0.36 ng/ml). The present study also confirmed that the increase in serum LH after intravenous injection of 50 ng GnRH was much smaller in old ovariectomized rats. These results show that the electrical activity of the GnRH pulse generator is certainly reduced with age. Taken together with findings suggesting an age-dependent decrease in stimulated transmitter release, attenuation in both frequency and amplitude of GnRH pulses as well as in pituitary responsiveness to GnRH pulses may account for the decreased pulsatile LH secretion observed in aging rats.