A novel approach to assess changes in endocrine secretion: analysis of GnRH antagonist (Nal-Glu) suppression of gonadotropin release in ovariectomized ewes

Department of Pediatrics, University of Michigan, Ann Arbor 48109-0404, USA.

Circulating hormone levels reflect the outcome of multiple feedback systems. A method to accurately assess the dynamics of hormonal changes in samples collected at infrequent intervals and compare these dynamic processes among treatment groups is presented. In this approach, a smooth curve is fitted to each time series of concentrations produced in an experiment, the curves are summarized by numerical measurements, and the measurements are subjected to statistical analysis. The method is demonstrated on data from an experiment that explores the differential effects of a competitive GnRH receptor antagonist (Nal-Glu) on circulating levels of LH and FSH. In this experiment, six adult ovariectomized Suffolk ewes were treated with one of three doses of Nal-Glu using a crossover design. LH and FSH concentrations were determined in hourly samples of jugular blood for 24 h after treatment. Applying the analytical approach, we observed differential effects of increasing concentrations of Nal-Glu on circulating LH and FSH concentrations. The magnitude of LH suppression was similar from dose to dose, while the duration of LH suppression was dose-dependent. In contrast, all doses of Nal-Glu elicited similar effects on the amplitude, duration and time to recovery of FSH suppression. Studies conducted in vitro utilizing dispersed ovine pituitary cells in culture demonstrated that the differential effects of Nal-Glu on FSH and LH secretion were not the outcome of differential sensitivity of FSH and LH to GnRH. The differential effects of Nal-Glu on circulating LH and FSH concentrations may be due to a number of factors, including other releasing or release-inhibiting hormones, paracrine modulators involved in selective regulation of FSH, and/or differences in clearances.

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