Resumption of Pulsatile Luteinizing Hormone Release after α-Adrenergic Stimulation in Aging Constant Estrous Rats*

The present studies attempt to define the nature of the impairment of the LH secretory response to ovariectomy in the old constant estrous (CE) rat. LH secretory patterns were characterized 2 weeks after ovariectomy in cannulated, previously normally cycling young (4–5 months old) and previously CE middle-aged (11–12 months old) and aged (21–23 months old) Long-Evans rats from which blood was sampled at 10-min intervals for 3 h. Young rats had the expected pulsatile LH secretion pattern, which was characterized by a mean LH level of 137 ± 8 ng/ml plasma, an LH pulse amplitude of 154 ± 12 ng/ ml plasma, and an LH pulse frequency of 1.16 ± 0.13 pulses/h. In marked contrast, only four of seven middle-aged and two of six old rats exhibited significant pulsatile LH secretion. Of these six animals with pulsatile LH profiles, only two had more than one LH pulse during the 3-h experimental period. The significant, large decreases in mean LH levels for middle-aged (45 ± 4 ng/ml plasma) and old (40 ± 4 ng/ml plasma) rats compared to young animals (137 ± 8 ng/ml plasma) appear to primarily result from the decrease in LH pulse frequency, although LH pulse amplitude was also moderately decreased with age. A single injection of the /-adrenergic agonist, clonidine HC1 (CLCN, 0.3 mg/kg body weight, iv) stimulated pulsatile LH secretion in nine of nine middle-aged rats and three of eight old rats. CLON increased pulse amplitude by 2-fold, pulse frequency by nearly 3-fold, and doubled mean LH concentrations in middle-aged rats. Although LH pulses in old, CLON-treated rats were similar in amplitude to those observed in CLON-treated middle-aged rats, they occurred less frequently. These data indicate that 2 weeks after ovariectomy (1) LH pulse frequency is more severely affected by age than LH pulse amplitude; (2) α-adrenergic stimulation can reinitiate relatively normal pulsatile LH secretion in middle-aged rats; and (3) the capacity of an a-adrenergic agonist to enhance pulsatile LH secretion declines with increasing age and/or length of time after the onset of constant estrus in Long- Evans rats.