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Characterization of Attenuated Proestrous Luteinizing Hormone Surges in Middle-Aged Rats by Deconvolution Analysis¹

^a Department of Obstetrics and Gynecology and ^b Department of Anatomy, Medical College of Virginia, Richmond, Virginia 23298 ^c Department of Biology, ^d Department of Internal Medicine, and ^e NSF Center for Biological Timing, University of Virginia, Charlottesville, Virginia 22908

Reproductive aging in female rats is associated with attenuated preovulatory LH surges. In this study, detailed analyses of the episodic characteristics of the proestrous LH surge were conducted in young and middle-aged regularly cyclic rats. On proestrus, blood samples were withdrawn at 3-min intervals for 6 h and analyzed for LH concentrations by RIA in triplicate. Deconvolution analysis of immunoreactive LH concentrations revealed that there was no difference in the detectable LH secretory burst frequency between young 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 young 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 with normal LH surges. The apparent half-life of endogenous LH was similar among the 3 groups. The attenuated LH surges of middle-aged rats were related 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 groups. Our findings of a markedly decreased amount of LH released per burst and preserved orderliness of the LH release process strongly suggest that a deficient 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 proestrous LH surge in middle age.

¹ This investigation was supported by NIH Grants R29-AG07452 (to D.W.M.), R01-AG14799 (to J.D.V.), R01-AG05977 (to W.S.E.); the University of Virginia Reproduction Research Center, P30-HD28934 (J.D.V., W.S.E.); and the University of Virginia National Science Foundation Center for Biological Timing.

² Correspondence: Dennis W. Matt, Department of Obstetrics and Gynecology, Medical College of Virginia, Box 34, Richmond, VA 23298. FAX: 804 828 0573; matt{at}hsc.vcu.edu

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