Naloxone stimulates comparable release of luteinizing hormone-releasing hormone from tissue fragments from ovariectomized, estrogen-treated young and middle-aged female rats

Abstract

Endogenous opioids play a role in the regulation of LH-RH neurosecretion throughout the estrous cycle and during the preovulatory LH surge on proestrus. Experimental evidence suggests that opioid influence may be altered with age, and it has been hypothesized that these alterations may contribute to the loss of regular estrous cyclicity in aging female rats. The present study utilizes an in vitro perifusion paradigm to compare the ability of opiate receptor blockade with naloxone to stimulate LH-RH release from tissue fragments from ovariectomized, estrogen-treated young and middle-aged females. Naloxone stimulated a greater than 50% increase in LH-RH release from most fragments that contained primarily LH-RH axons and terminals and from all tissue fragments that contained the majority of LH-RH cell bodies as well as axons and terminals. The LH-RH response to naloxone administration was qualitatively, quantitatively and temporally comparable in tissue fragments from young and middle-aged animals. These data suggest that LH-RH neurosecretion in ovx, estrogen-primed middle-aged female rats remains under the inhibitory influence of endogenous opioid peptides. Although in vitro LH-RH release did not differ in response to naloxone, age-related differences in naloxone's ability to increase serum LH levels in vivo were observed. The data are discussed with regard to potential age-related differences in pituitary responsiveness to LH-RH and in other systems that enhance pituitary responsiveness to LH-RH as well as alterations in excitatory or inhibitory influences that may have been eliminated in the in vitro protocol.