Isolated hypothalami from aging female rats do not exhibit reduced basal or potassium-stimulated secretion of luteinizing hormone-releasing hormone.

Serum LH levels are diminished in middle-aged rats during spontaneous or steroid-induced LH surges and following ovariectomy (ovx). The compromised LH responses are presumed to reflect age-related alterations in LHRH neurosecretion. Direct measurements of LHRH output in middle-aged females are, however, limited. The present study utilizes an in vitro perifusion paradigm to assess basal and stimulated secretory capacity of LHRH neurons in isolated hypothalamic preparations from aging female rats. Individual hypothalamic fragments from middle-aged and young proestrous, ovx, and ovx, estradiol-treated females were perifused for 6 h and effluents were collected continuously at 10-min intervals. After 4 h of unstimulated output, two 10-min depolarizing pulses of KCl were administered. Although stimulated LHRH secretion was comparable in the two age groups, basal LHRH release from aging hypothalami was significantly elevated (pbasal less than 0.001). Furthermore, endocrine influences on LHRH output from aging hypothalami were less pronounced when compared to endocrine influences on LHRH output from young hypothalami, suggesting that steroidal regulation of LHRH secretion may be impaired in middle-aged females. These data demonstrate that LHRH neurons maintain the capacity to respond to a depolarizing stimulus at the time when regular estrous cycles cease and consequently suggest the importance of altered modulation of LHRH neurosecretion to the development of reproductive senescence.