title: Ethanol and estradiol modulate alternative splicing of dopamine D2 receptor messenger RNA and abolish the inhibitory action of bromocriptine on prolactin release from the pituitary gland.
abstract: BACKGROUND
  Several reports show evidence for the existence of high levels of prolactin (PRL) in alcoholic men and women. Previously we have shown that ethanol increases PRL release both in vivo and in vitro. How ethanol increases PRL release is not well understood.
  
  
  METHODS
  In this study, we determined the effects of ethanol in the presence and absence of estradiol-17 beta on PRL messenger RNA (mRNA) levels, dopamine D2 receptor mRNA splicing, and the PRL-inhibitory response of a dopaminergic agent, bromocriptine, in the pituitary of Fischer-344 rats and in primary cultures of anterior pituitary cells. Real-time reverse transcriptase-polymerase chain reaction was used for mRNA detection, and radioimmunoassay was used for hormone detection.
  
  
  RESULTS
  Estradiol and ethanol alone increased PRL mRNA expression in the pituitary gland. Ethanol also potentiated estradiol action on PRL mRNA expression in the pituitary. Determination of the D2 receptor splicing, by determining the changes in the percentage of D2 receptor mRNA expressed as its long form (D2L) and as its short form (D2S), revealed that both ethanol and estradiol altered D2 receptor splicing. Ethanol and estradiol, alone and together, increased the percentage of the D2L receptor but decreased the D2S receptor percentage. Similarly, ethanol and estradiol alone and in combination increased D2L, but decreased the D2S receptor percentage in primary cultures of pituitary cells. Evaluation of bromocriptine's inhibition of PRL release in primary cultures of pituitary cells indicated that ethanol reduced the ability of this D2 receptor agonist to inhibit PRL release.
  
  
  CONCLUSIONS
  These results confirm estradiol's inhibition of D2 function and provide novel evidence that ethanol, like estradiol, reduces dopamine's ability to inhibit PRL release by modifying alternative splicing of the dopamine D2 receptor in the pituitary.
authors.affiliation: Endocrinology Program, Biomedical Division, Center of Alcohol Studies and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, 08901, USA.
authors.forename: Souichi
authors.initials: S
authors.lastname: Oomizu
authors.forename: Nadka
authors.initials: N
authors.lastname: Boyadjieva
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Sarkar
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001971:Bromocriptine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D000431:Ethanol; D004958:Estradiol; D011388:Prolactin