Evidence for sexual dimorphism of estrogen receptors in hypothalamus and thymus of neonatal and immature Wistar rats

It is hypothesized that the rat thymus is sexually differentiated. To begin testing this, we used the 5-day-old rat, whose hypothalamus is sexually di fferentiated during this period. Cytosolic estrogen receptors (ER) were mea sured in cytosols prepared from the brain, thymus and uterus of Wistar rats at 5, 18 and 30 days post-partum. ER concentrations were significantly hig her in hypothalamus in cytosols of female 5-day-old rats, and this differen ce had disappeared by day 18. The pattern in thymus was identical to that o bserved in hypothalamus, suggesting the presence in the thymus of the aroma tase system that converts androgen to estrogen, and that estrogen-mediated sexual differentiation of thymus might be proceeding at 5 days. Unlike the case for hypothalamus, no experimental model exists at present for testing functional sexual differentiation in thymus. Therefore we tested the effect s of aromatase inhibitors on estrogen receptor activity in thymus well afte r the five-day period, and before atrophy of the thymus has commenced. Male and female rats were implanted at 15 days of age with SILASTIC implants co ntaining 5 mg of estradiol or with 25 mg of the aromatase inhibitor 4-hydro xyandrostenedione (4-OHA) and cytosolic ER prepared at 30 days and activity measured. Administration of estradiol resulted in failure to detect availa ble receptor, suggesting that the binding components measured were ER. Afte r 4-OHA administration, ER concentrations were significantly increased in c ytosols from male but not female hypothalamus and thymus, There is therefor e a basis for exploring further the hypothesis that rat thymus is sexually differentiated. (C) 1999 International Society for Immunopharmacology. Publ ished by Elsevier Science Ltd. All rights reserved.