PARENT SESSION
SLIDE SESSION 13: GONADAL FUNCTION
Chairs: Robert Burghart, Francisco Moran (Trainee)
Univ Ottawa-Monpetit 203
1:30 PM-3:30 PM

EFFECTS OF SB75, A GONADOTROPIN RELEASING HORMONE ANTAGONIST, ON TESTIS GROWTH AND KEY ENZYMES OF THE STEROIDOGENIC PATHWAY IN THE NEONATAL PIG.

Moran, Francisco¹, Ford, Joe², Conley, Alan¹, ^{1 2}

ABSTRACT- Cytochromes P450 17-hydroxylase/17,20-lyase (P450c17) and aromatase (P450arom) together with the redox partner proteins, NADPH-cytochrome P450 reductase (reductase) and cytochrome b5 (b5) catalyze the synthesis of androgen and estrogen by the pig testis. Gonadotropins are thought to induce and maintain not only testis weight, but also steroidogenic enzyme expression. A gonadotropin-releasing hormone antagonist (SB75) was used to examine the effect of inhibition of gonadotropin secretion on testis growth, and Leydig cell differentiation in the neonatal pig. Sixteen, day-old piglets received vehicle or treatment (SB75, 50 mg/Kg/day) for 7 or 14 days. Additional controls were castrated on day 1 and 24 of age. Circulating LH was determined by radioimmunoassay. Testis microsomes were used for total P450 concentration, protein expression and enzyme activity analysis. There was an increase in the control group from day 1 to day 24 for both P450arom and 17,20-lyase activity. P450 concentration increased from day 1 to 7 and remained unchanged until day 24. There were no differences on day 7 and day 14 in the treated animals. Treatment suppressed (P<0.01) the increase in LH, testis weight and P450arom activity. Increase in17, 20-lyase activity was also reduced (P<0.05) by treatment. P450 concentration was depressed by treatment, (P<0.01) only after 7 days. Reductase activity was not reduced. There was a strong correlation among LH levels, enzyme activities and protein expression. No change was noted in b5 expression. While it is possible that SB75 had a direct effect on the testes, we interpret these data to suggest that gonadotropic support is critical for testis growth and P450arom induction during the first two weeks of life. We conclude that SB75 blocked gonadotropic induction of testes growth, P450arom protein levels and activity, less dramatically reduced P450c17 and reductase, and had no effect on b5 protein expression. Supported by USDA-NRI 98-35203-6439

KEY WORDS: aromatase, lyase, testis, neonatal pig