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ARS Home » Pacific West Area » Dubois, Idaho » Range Sheep Production Efficiency Research » Research » Publications at this Location » Publication #161799
Title: FETAL EXPOSURE TO AN AROMATASE INHIBITOR ALTERS SECRETION OF LUTEINIZING HORMONE IN CASTRATED POST-PUBERTAL RAMS

Author
item SCHRUNK, JESSICA - OREGON STATE UNIVERSITY
item Stellflug, John
item ROSELLI, CHARLES - OREGON HEALTH SCIENCE
item STORMSHAK, FREDRICK - OREGON STATE UNIVERSITY

Submitted to: Society for the Study of Reproduction Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 7/1/2004
Publication Date: 7/1/2004
Citation: Schrunk, J.M., Stellflug, J.N., Roselli, C.E., Stormshak, F. 2004. Fetal exposure to an aromatase inhibitor alters secretion of luteinizing hormone in castratedpost-pubertal rams [abstract]. Biology of Reproduction. 71(1):220.

Interpretive Summary: Conversion of testosterone to estrogen in the male brain by aromatase enzyme is crucial for defeminization and masculinization of the brain. To examine the role of estrogen in sexual differentiation of the male ovine brain, pregnant ewes were treated with an aromatase inhibitor, to block the conversion of testosterone to estrogen. Pregnant ewes were given daily subcutaneous injections of either polyethylene glycol (vehicle, n=10) or of aromatase inhibitor (n=10) from Days 50 to 80 of pregnancy. At 20 mo of age, eight rams, four from control and four from treated ewes, were castrated. Five mo after castration, rams were given estrogen intramuscularly to determine whether in utero exposure to aromatase inhibitor would cause these rams to exhibit a luteinizing hormone surge, thus suggesting that defeminization of the brain had failed to occur. Injection of estrogen failed to provoke a luteinizing hormone surge in either group, but basal levels of luteinizing hormone were significantly lower in aromatase inhibitor-treated rams than in controls. To determine whether altered basal luteinizing hormone secretion was due to an effect of the aromatase inhibitor at the level of the hypothalamus or the pituitary (specific brain regions), rams were administered gonadotropin-releasing hormone. At 30 mo, the same castrated rams were given gonadotropin-releasing hormone intravenously. Injection of gonadotropin-releasing hormone caused a significant increase in luteinizing hormone secretion in both control and aromatase inhibitor-treated rams, but the surge release of luteinizing hormone did not differ. However, as after injection of estrogen, basal levels of luteinizing hormone in rams exposed to aromatase inhibitor were significantly lower than in controls. These data suggest that the lower basal luteinizing hormone levels in aromatase inhibitor treated-rams represent a difference in the brain function supporting the hypothesis that aromatization of testosterone to estrogen plays a crucial role in the developing male brain.

Technical Abstract: Conversion of testosterone (T) to estradiol-17ß (E2) in the male brain by aromatase is crucial for defeminization and masculinization of the hypothalamus. To examine the role of estrogen in sexual differentiation of the male ovine brain, pregnant ewes were treated with 1,4,6-androstatriene-3,17-dione (ATD), an aromatase inhibitor, to block the conversion of T to E2. Twenty ewes were given s.c. injections of either 3 ml polyethylene glycol (vehicle, n=10) or 100 mg/day ATD (n=10) from Days 50 to 80 of gestation. At 20 mo of age, eight rams, four from control and four from treated ewes, were castrated. Five mo after castration rams were given 50 µg E2 i.m. to determine whether in utero exposure to ATD would cause these rams to exhibit an LH surge, thus suggesting that defeminization of the hypothalamus had failed to occur. Prior to E2 challenge (0 h), blood was drawn hourly for 4 h to determine basal levels of LH, and then subsequently every 2 h for 36 h. Serum was collected and stored frozen until analyzed for LH by use of RIA. The resulting data on serum concentrations of LH were analyzed statistically by ANOVA . Injection of E2 failed to provoke an LH surge in either group, but basal levels of LH were lower (P<0.05) in ATD-treated rams than in controls. To determine whether altered basal LH secretion was due to an effect of the ATD at the level of the hypothalamus or the pituitary, rams were administered GnRH. At 30 mo, the same castrated rams were given 100 µg GnRH i.v. at 0 h. Blood samples were collected at 15 min intervals for 1 h prior to and after GnRH challenge, and then at 30 min intervals for the following 2 h. Serum was collected, analyzed for LH concentrations, and the data evaluated statistically as described above. Injection of GnRH caused a significant increase in LH secretion in both control and ATD-exposed rams, but the surge release of LH did not differ (P>0.05). However, as after injection of E2, basal levels of LH in rams exposed to ATD were lower than in controls (P<0.05). These data suggest that the lower basal LH levels in these rams represent a difference in the hypothalamic function supporting the hypothesis that aromatization of T to E2 plays a crucial role in the developing male brain. Research supported by NIH NCRR grant R01RR014270.