Steroid Hormones and Receptors of the GABAA Supramolecular Complex

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Abstract
The effects of sex steroid hormones on the different receptor binding sites of the GABAA molecule remain unclear. In this report we have demonstrated, using autoradiography techniques, that the distribution pattern of the benzodiazepine receptors (a component of the GABAA molecule) in some extrahypothalamic brain regions is altered by both in vivo and in vitro sex steroid hormone treatment. In vivo administration of the sex steroids estradiol and progesterone induced a significant change in [3H]flunitrazepam (benzodiazepine agonist) binding levels in the amygdala, and cortico and posterior brain nuclei of the female rat. In fact, elevated and diminished receptor-binding levels were obtained in the corticomedial amygdala nucleus and in the pontine central gray matter respectively, following the administration of estradiol. Significant hormonal effects were also shown for animals that received only a progesterone dose, as demonstrated by the increased and decreased receptor levels in the basolateral amygdala nucleus and cortex lamina VI and in the substantia nigra pars reticulata, respectively. It was interesting, at this point, to investigate whether the hormone effects on [3H]flunitrazepam binding changes might be mediated through a GABA-dependent activity, because the benzodiazepine and GABAA receptors are coupled to a chloride ion channel in an allosteric manner. When 50 microM GABA was added to the incubation medium, substantially altered binding levels were recorded in animals that received progesterone replacement therapy only. The GABA-induced progesterone effects both increased substantially the binding levels in the oriens-pyramidalis CA1 layer of the hippocampus and in the intermediate gray layer of the superior colliculus as well as reducing receptor levels in the substantia nigra pars reticulata.(ABSTRACT TRUNCATED AT 250 WORDS)

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