Effect of androgens on sexual differentiation of pituitary gamma-aminobutyric acid receptor subunit GABAB expression

María S. Bianchi, Paolo N. Catalano, María M. Bonaventura, Patricia Silveyra, Bernhard Bettler, Carlos Libertun, Victoria A.R. Lux-Lantos

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Abstract

Previous work demonstrated a sexually dimorphic ontogenic expression of γ-aminobutyric acid receptors (GABABR) in rat pituitary. As sex steroids determine sex-specific expression patterns, we now studied the effect of sex hormones on pituitary GABABR expression. GABABR subunits, measured by Western blot and by semi-quantitative RT-PCR and luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone measured by RIA were determined in two experimental designs: First experimental design: 8- and 15-day-old females (8F, 15F); 8F and 15F treated with 100 μg testosterone propionate (TP) on day 1 of life (8F100TP, 15F100TP), 8- and 15-day-old males (8M, 15M) and 8M and 15M castrated on day 1 (8MC, 15MC). Second experimental design: 8-day-old female and male animals: 8F, 8F100TP, 8F treated with 1 μg/day TP on days 1-4 (8F1TP), 8F treated with the androgen antagonist Flutamide (Flut: 2.5 mg/100 g BW of pregnant mother on days E17-E23) (8F-Flut), 8M, 8MC, 8M treated with Flut as above (8M-Flut) and 8MC-Flut. In these animals, in addition, GABA, glutamate, aspartate and taurine were measured by HPLC in hypothalami and cortex. In the first set of experiments, GABA B1R mRNA/protein expression was higher in 8F than in 15F, 8M or 15M. In 8F100TP, GABAB1R mRNA/protein decreased to male levels. TP treatment did not alter GABAB1R expression in 15F. There was no difference in GABAB1R expression between 8M and 15M and neonatal castration did not modify its expression. In the second set of experiments, TP (1 μg) or Flut did not modify GABAB1R in 8F, while 100 μg TP continued to decrease GABAB1R expression. In 8M, Flut, alone or with castration, increased GABAB1R mRNA/protein expression to 8F. Hypothalamic GABA content followed the same pattern as pituitary GABABR expression in 8-day-old animals, suggesting a cross-regulation. With regard to hormonal levels, 100 μg, but not 1 μg TP altered gonadotropins at 8 days, although both treatments effectively androgenized females as evidenced by lack of cycling. We conclude that androgens, acting pre- and postnatally, decrease pituitary GABABR subunit expression.

Original languageEnglish (US)
Pages (from-to)129-142
Number of pages14
JournalNeuroendocrinology
Volume80
Issue number3
DOIs
StatePublished - Dec 1 2004

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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    Bianchi, M. S., Catalano, P. N., Bonaventura, M. M., Silveyra, P., Bettler, B., Libertun, C., & Lux-Lantos, V. A. R. (2004). Effect of androgens on sexual differentiation of pituitary gamma-aminobutyric acid receptor subunit GABAB expression. Neuroendocrinology, 80(3), 129-142. https://doi.org/10.1159/000082527