A NOVEL-APPROACH TO ASSESS CHANGES IN ENDOCRINE SECRETION - ANALYSIS OF GNRH ANTAGONIST (NAL-GLU) SUPPRESSION OF GONADOTROPIN-RELEASE IN OVARIECTOMIZED EWES

Circulating hormone levels reflect the outcome of multiple feedback sy stems, 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 sm ooth curve is fitted to each time series of concentrations produced in an experiment, the curves are summarized by numerical measurements, a nd the measurements are subjected to statistical analysis. The method is demonstrated on data from an experiment that explores the different ial effects of a competitive GnRH receptor antagonist (Nal-Glu) on cir culating levels of LH and FSH. In this experiment, six adult ovariecto mized Suffolk ewes were treated with one of three doses of Nal-Glu usi ng a crossover design, LH and FSH concentrations were determined in ho urly samples of jugular blood for 24 h after treatment. Applying the a nalytical approach, we observed differential effects of increasing con centrations of Nal-Glu on circulating LH and FSH concentrations, The m agnitude of LH suppression was similar from dose to dose, while the du ration 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 d ispersed ovine pituitary cells in culture demonstrated that the differ ential effects of Nal-Glu on FSH and LH secretion were not the outcome of differential sensitivity of FSH and LH to GnRH. The differential e ffects of Nal-Glu on circulating LH and FSH concentrations may be due to a number of factors, including other releasing or release-inhibitin g hormones, paracrine modulators involved in selective regulation of F SH, and/or differences in clearances.