Aging-related reduced release of LH-releasing hormone from hypothalamic granules

The effects of aging on the secretory function of hypothalamic granules containing luteinizing hormone releasing hormone (LHRH) were examined, using chelated copper as a test substance. Granules prepared from old and young female rats were each incubated with various concentrations of CuATP and the kinetic constants of LHRH release estimated. The LHRH content of the hypothalamus of old female rats (3.4 +/- 0.1 ng; mean +/- S.E.; n = 3 determinations) was lower than that of young female rats (4.7 +/- 0.1 ng; n = 3). CuATP-stimulated LHRH release (pg/hypothalamus) from granules isolated from old animals was significantly (p less than 0.001) lower than that from granules isolated from young animals; Vmax being 58.5 +/- 1.6 pg (n = 36) and 76.7 +/- 2.7 pg (n = 34) of LHRH released/min, respectively. In contrast, the fractional amount of CuATP-stimulated release of LHRH from granules isolated from old and young rats was similar; Vmax being 60 +/- 0.5% and 62 +/- 1% of granule LHRH released, respectively. In addition, the apparent Km for CuATP-stimulated release of LHRH from granules of old and young rats was also similar, 5.1 and 5.5 microM copper, respectively. These results are suggestive that aging does not alter the responsiveness of LHRH-containing granules to a secretion-stimulus such as copper but it does alter the capacity (amount) of peptide released.