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

Abstract

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.