Characterization of attenuated proestrous luteinizing hormone surges in middle-aged rats by deconvolution analysis

Reproductive aging in female rats is associated with attenuated preovulator y LH surges. In this study, detailed analyses of the episodic characteristi cs of the proestrous LH surge were conducted in young and middle-aged regul arly cyclic rats. On proestrus, blood samples were withdrawn at 3-min inter vals for 6 h and analyzed for LH concentrations by RIA in triplicate. Decon volution analysis of immunoreactive LH concentrations revealed that there w as no difference in the detectable LH secretory burst frequency between you ng and middle-aged rats. However, in middle-aged rats with an attenuated LH surge on proestrus, the mass of LH secreted per burst and the maximal rate of LH secretion per burst were only one fourth (p < 0.01) of those in youn g and middle-aged rats with normal LH surges. Furthermore, middle-aged rats with attenuated LH surges had a 4-fold decrease (p < 0.01) in the maximal rate of LH secretion per burst compared to young and middle-aged females wi th nor mal LH surges. The apparent half-life of endogenous LH was similar a mong the 3 groups. The attenuated LH surges of middle-aged rats were relate d specifically to a decrease in LH burst amplitude with no change in pulse frequency. The orderliness of moment-to-moment LH release as quantified by the regularity statistic, approximate entropy, was comparable in the 3 grou ps. Our findings of a markedly decreased amount of LH released per burst an d preserved orderliness of the LH release process strongly suggest that a d eficient GnRH drive and/or reduced responsivity to the GnRH signal, rather than altered timing of the signal, accounts for the age-related decline in reproductive function in female rats as presaged by an attenuated proestrou s LH surge in middle age.