Pituitary GABAB receptor subunit expression: effect of testosterone (T) and sexual differentiation

C LIBERTUN; M BIANCHI; M FERNANDEZ; P CATALANO; B BETTLER; V LUX-LANTOS

New York, USA

Congreso; Eighth International Pituitary Congress; 2003

A clear sexually dimorphic ontogenic expression of GABAB receptor (RGABAB) subunits in rat pituitary membranes has been shown (Neuropharmacology 40:185-192:2001). Here we investigated the role of perinatal testosterone on RGABAB subunit expression. Rat groups: 8 day-old females (8F); 8F treated with 1 mg/day of TP on days 1-4; 8F treated with 100 mg TP on day 1; 8F treated with flutamide (FL: 2.5 mg/100g BW of pregnant mother, embryonic days 17-23), 8 day-old males (8M), 8M castrated on day 1, 8M treated with FL as above; 8M treated with FL and castrated on day 1; 15 day-old females (15F); 15F treated with 100 mg TP on day 1; 15 day-old males (15M) and 15M castrated on day 1. Rats were decapitated on day 8 or 15, trunk and pituitaries collected and frozen. R-GABA-B subunit expression was determined on pituitary membranes by Western Blot with antiserum Ab 174.1 which detects GABAB1a/b subunits, using a syntaxin expression to ensure comparable protein load. Hormones were determined by RIA. GABAB1a and GABAB1b expression was higher in 8F than in 15F or 8M (GABAB1a (AU): 8F: 0.98±0.08 vs 15F: 0.46±0.6 vs 8M: 0.56±0.02, p<0.01). 100 mg TP in 8F, but not in 15F, decreased RGABAB subunit expression to male levels (p<0.05). 1mg TP, or FL, in 8F did not alter subunit expression. In 8M, FL treatment, alone or with castration, increased subunit expression to 8F levels, though castration alone was not effective (GABAB1a (AU): 8M-castr: 0.67±0.06, 8M-FL: 0.81±0.05, 8M-Fl-castr: 0.97±0.03). 100 mg TP, but not 1mg TP, profoundly altered serum gonadotropins at 8 days of life, though both treatments effectively adrogenized animals, as evidenced by lack of cycling and LH surge in rats reaching adulthood. We conclude that androgens, acting pre- and post-natally, decrease pituitary RGABAB subunit expression.