In adult female rats, giving GnRH‑agonist drugs (normally used to control hormone release) made the thymus gland larger and raised the amount of thymosin‑alpha‑1, a peptide that helps the immune system. The biggest growth happened about 18 days after starting the drug and was reversed when estrogen was added. The gland got bigger without a clear increase in cell division, and the change was linked to lower reproductive hormone levels.

The potential clinical applications of GnRH agonists are growing. We studied the effects of two GnRH agonists on the adult female rat thymus in 4 experiments. GnRH agonists administered sc and continuously significantly increased wet and dry thymic weights (absolute and relative). Thymic enlargement was related to the duration of treatment with GnRH agonists. The maximum increase in thymic weight occurred at approximately 18 days following initiation of treatment with GnRH agonists. Thymic enlargement does not appear to involve enhanced mitotic activity as measured by incorporation of tritiated thymidine into thymic tissue and thymic DNA. Histologic examination and computer-assisted morphometric analysis of thymuses indicated an increase in cortex to medulla ratio most pronounced at 10 and 18 days of GnRH agonist treatment. No consistent increases in splenic weight or bone marrow cell counts were observed. Thymosin alpha-1 but not thymosin beta-4 increased in GnRH agonist-treated rats. Thymic weight correlated negatively with ovarian and uterine weights, relative adrenal weight, serum estradiol, LH, and positively with thymosin alpha-1. Exogenous estrogen administration reversed GnRH agonist-induced thymic weight increase. Whether GnRH agonists have direct thymic effects remains to be determined.