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*

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Abstract
These studies assessed the effects of age on the ability of estradiol-17.beta. (E2) to induce luteinizing hormone [LH] and prolactin [PRL] surges in ovariectomized young and middle-aged rats that previously had normal estrous cycles. Whether any changes in the timing or amplitude of these surges could be correlated with changes in pituitary responsiveness to gonadoliberin [GnRH] or with changes in norepinephrine (NE) and dopamine (DA) turnover rates in microdissected brain regions involved in cyclic gonadotropin release was determined. Young (3-4 mo. old) and middle-aged (9-12 mo. 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 middle-aged rats. E2-induced PRL surges did not exhibit any age-related differences. Pituitary responsiveness to GnRH was tested by administering 2 injections of GnRH to pentobarbital-blocked young and middle-aged rats on days 2 and 4. Pituitary responsiveness to the 1st injection on day 2 was blunted in middle-aged rats. The LH response at all other times was normal. Catecholamine turnover rates were examined on days 2 and 4 by giving .alpha.-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 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 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.