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Gonadotropin-releasing Hormone Agonist Administration Affects the Thymopoiesis in Adult Female Rats Independently on Gonadal Hormone Production


Address reprint requests to Gordana Leposavić, Department of Physiology, Faculty of Pharmacy, 450 Vojvode Stepe, 11221 Belgrade (Kumodraž), Serbia and Montenegro.


Problem:  In addition to having an indirect effect on the T-cell development by controlling the production of ovarian steroids, an accumulating body of evidence suggest that GnRH analogue (GnRH-A) administration may exert a thymopoietic regulatory effect that is not mediated by ovarian hormones.

Method of study:  In non-ovariectomized (non-OVX) and OVX adult female AO rats treated s.c. with GnRH-A or saline (controls), over 14 days, were estimated the thymic cellularity and thymocyte expression of CD4/CD8/TCRαβ by stereological analysis and three-color flow cytometry, respectively.

Results:  GnRH-A in both groups of rats diminished the thymic cellularity. In non-OVX rats GnRH-A increased the relative numbers of immature cells (CD4-8-TCRαβ, CD4-8-TCRαβlow and CD4+8-TCRαβlow), and reduced those of positively selected CD4+8+TCRαβhigh and mature (CD4-8+TCRαβhigh, CD4+8-TCRαβhigh) cells, suggesting decelerated expression of TCRαβ followed by less efficient positive selection and further maturation of the selected cells. Differently, in OVX rats GnRH-A decreased the percentage of immature (CD4-8-TCRαβ, CD4+8+ TCRαβ) cells and increased those of all TCRαβhigh subsets, suggesting an increased rate of early thymocyte differentiation, more efficient positive selection and further maturation of the selected cells.

Conclusions:  The effect of GnRH-A administration is affected by the presence of ovarian steroids.