Sex steroid hormones change the differential distribution of the isoforms of the D2 dopamine receptor messenger RNA in the rat brain.
The two isoforms of the rat dopamine D2 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 D2L is predominant in the pituitary gland, the striatum and to a lesser extend in the olfactory tubercle, whereas the short isoform D2S 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 D2 receptor messenger RNA. Castration of male rats increased the ratio D2L/D2S 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, 17beta-estradiol had a similar effect to that of testosterone in the olfactory tubercle, indicating that testosterone may act after aromatization of estradiol. In the hypothalamus, 17beta-estradiol alone reversed the effect of castration. In the striatum, neither castration nor hormonal treatments modified the splicing of the D2 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.
Guivarc'h
D
D
Institut Alfred Fessard, UPR 2212, C.N.R.S., Gif-sur-Yvette, France.
Vernier
P
P
Vincent
J D
JD
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D007536:Isomerism; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D009919:Orchiectomy; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D013739:Testosterone / Q000494:pharmacology*; D014018:Tissue Distribution
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D013739:Testosterone; D004958:Estradiol