SEX STEROID-HORMONES CHANGE THE DIFFERENTIAL DISTRIBUTION OF THE ISOFORMS OF THE D-2 DOPAMINE-RECEPTOR MESSENGER-RNA IN THE RAT-BRAIN

The two isoforms of the rat dopamine D-2 receptor are generated by alternative splicing of the pre-messenger RNA and differ in the length of their third cytoplasmic loop involved in coupling to G-proteins. As quantified by polymerase chain reaction, the long isoform D-2L is predominant in the pituitary gland, the striatum and to a lesser extend in the olfactory tubercle, whereas the short isoform D-2S is relatively more abundant in the hypothalamus and the substantia nigra. Changes in circulating sex hormone levels modulated the splicing without affecting the total amount of D-2 receptor messenger RNA. Castration of male rats increased the ratio D-2L/D-2S in the pituitary, hypothalamus and substantia nigra, and decreased it in the olfactory tubercle. Testosterone substitution reversed the effect of castration in the pituitary and olfactory tubercle but not in the substantia nigra. In castrated rats, 17 beta-estradiol had a similar effect to that of testosterone in the olfactory tubercle, indicating that testosterone may act after aromatization to estradiol. In the hypothalamus, 17 beta-estradiol alone reversed the effect of castration. In the striatum, neither castration nor hormonal treatments modified the splicing of the D-2 receptor mRNA. Treatment of animals with specific androgen and estrogen receptor blockers confirmed that steroids were acting through their specific intracellular receptors. These observations suggest a molecular mechanism, physiologically relevant, by which circulating sex hormones could modulate dopamine transmission in areas implicated in reproductive and parental behaviours.