Estradiol-induced daily luteinizing hormone and prolactin surges in young and middle-aged rats: Correlations with age-related changes in pituitary responsiveness and catecholamine turnover rates in microdissected brain areas

These studies assessed the effects of age on the ability of estradiol-17β (E₂) to induce LH and PRL surges in ovariectomized young and middle-aged rats that previously had normal estrous cycles. We determined whether any changes in the timing or amplitude of these surges could be correlated with changes in pituitary responsiveness to GnRH or with changes in norepinephrine (NE) and dopamine (DA) turnover rates in microdissected brain regions involved in cyclic gonadotropin release. Young (3-4 months old) and middle-aged (9-12 months old) rats were ovariectomized. One week later (day 0), they received Silastic capsules containing E₂ which produced physiological serum concentrations of E₂. Groups of rats were bled sequentially via indwelling right atrial cannulae 1-4 days after capsule implantation (days 1-4). All young rats displayed maximal LH surges by day 2 and exhibited equivalent surges on days 3 and 4. Middle-aged rats required the presence of E₂ for at least 3 days before a maximal positive feedback response was achieved. Even at these times the timing of the LH rise was delayed by 1 h and peak concentrations were lower in middleaged rats. E₂-induced PRL surges did not exhibit any age-related differences. Pituitary responsiveness to GnRH was tested by administering two injections of GnRH to pentobarbital-blocked young and middle-aged rats on days 2 and 4. Pituitary responsiveness to the first injection on day 2 was blunted in middleaged rats; however, the LH response at all other times was normal. Catecholamine turnover rates were examined on days 2 and 4 by giving α-methyl-para-tyrosine at 1000 or 1500 h and killing rats 45 or 90 min later. Resting initial catecholamine concentrations were assessed in untreated rats killed at 1000 h or 1500 h. The medial preoptic nucleus, suprachiasmatic nucleus, and median eminence were microdissected and assayed for NE and DA by radioenzymatic assay. In young rats, NE turnover rates increased during the afternoon in all brain areas on both days. In contrast, in middle-aged rats, no increase in NE turnover rates was observed during the afternoon of day 2. By day 4, the delayed and attenuated LH surge was accompanied by increased turnover rates in the median eminence only; no change occurred in the suprachiasmatic nucleus or medial preoptic nucleus. No age-related differences were observed in DA turnover rates. The data suggest that the altered ability of E₂ to induce LH surges in ovariectomized middle-aged rats may be related to a transitory decrease in pituitary responsiveness to GnRH stimulation and to more persistent changes in the pattern of NE turnover.