Relation of attenuated proestrous luteinizing hormone surges in middle-aged female rats to in vitro pituitary gonadotropin-releasing hormone responsiveness.

Prior to the cessation of regular cyclicity, middle-aged rats display pre-ovulatory luteinizing hormone (LH) surges of reduced magnitude. The present study was designed to identify whether middle-aged female rats with attenuated proestrous LH surges have alterations in pituitary responsiveness to gonadotropin-releasing hormone (GnRH). Young (4 months old) and middle-aged (10-12 months old) regularly cycling females were catheterized and sampled on proestrus to characterize their LH surge profiles. On the next proestrus (12.00 h), pituitaries were perifused individually and exposed to three pulses of GnRH (30 nmol/1). The patterns of the proestrous LH surges revealed that 12 of 22 middle-aged rats had attenuated surges (< 7 micrograms/l) while the remaining 10 middle-aged females had surges that were similar to those of young rats. Pituitaries perifused on the next proestrus showed similar basal LH release among the middle-aged and young females. However, the LH secretory rates following the second and third administration of GnRH, as well as the overall GnRH-stimulated LH secretory rates, were significantly decreased in middle-aged females with previously attenuated LH surges as compared to those from the young proestrous rats. In contrast, middle-aged rats with normal LH surges had pituitary LH responses that were no different from those of young females. These results indicate that a decrease in pituitary LH responsiveness to GnRH is only apparent in middle-aged rats that display attenuated proestrous LH surges.