Adenohypophyseal and hypothalamic GABA B receptor subunits are downregulated by estradiol in adult female rats

ESTELA B. REY-ROLDÁN; MARÍA S. BIANCHI; BERNHARD BETTLER; DAMASIA BECU-VILLALOBOS; VICTORIA A. LUX-LANTOS; CARLOS LIBERTUN

LIFE SCIENCES

Año: 2006 vol. 79 p. 342 - 350

0024-3205

Gamma-aminobutyric acid (GABA) participates in neuroendocrine regulation. Since steroid hormones have been shown to modulate the GABAergic system, here we evaluated the effect of chronic in vivo estradiol administration on GABA B receptor (GABABR) expression. GABAB1 and GABAB2 subunits were analyzed by Western Blot and RT-PCR, in hypothalami and anterior pituitaries of adult female rats: a) treated for 1 week with estradiol-valerate (a single dose of 100 mg /kg: E1), b) implanted with a 10 mg pellet of estradiol-benzoate for 5 weeks (E5) or c) on proestrous (P) d) ovariectomized (OVX). Pituitary GABABR levels were correlated to a biological effect: baclofen, a GABABR agonist, action on intracellular calcium titers ([Ca2+]i) in pituitary cells. E5 pituitaries showed a significant decrease in the expression of GABAB1 and GABAB2 mRNAs compared to P. The GABAB1a splice variant of GABAB1 was always more abundant than GABAB1b in this tissue. Similar to the pituitary, hypothalamic GABAB1 and GABAB2 mRNAs decreased in E5; this was confirmed at the protein level. In the hypothalamus GABAB1b was the main variant expressed in P rats, and was the one significantly sensitive to estradiol-induced decrease, as determined by Western Blots. Castration did not modify GABABR expression with regards to P in either tissue. In P pituitary cells baclofen induced a decrease in [Ca2+]i, in contrast this effect was lost in E5 cells. We conclude that chronic estradiol treatment negatively regulates the expression of the GABABR subunits in the pituitary and the hypothalamus. This effect is coupled to a loss of baclofen action on intracellular calcium in pituitary cells.