Dopamine and sex steroid regulation of POMC gene expression in the hypothalamus.
Previous studies have shown that POMC mRNA and peptide levels are increased in the medial basal hypothalamus (MBH) of the chronically castrated rat and are suppressed with sex steroid replacement. In a parallel time course, hypothalamic dopamine turnover similarly changes after chronic castration and sex steroid replacement. In this study we have examined the effects of dopamine on POMC in the MBH and questioned whether the increase in dopamine activity which occurs in the MBH of chronically castrated rats is responsible for the stimulation of POMC seen under these conditions. We have therefore measured POMC gene expression and peptide content in the MBH of chronically castrated male and female rats in response to the dopamine antagonist haloperidol, and in intact or sex steroid replaced animals in response to the dopamine agonist pergolide. Adult male and female rats were studied 3-4 weeks after castration with and without testosterone (T) or estradiol (E2) replacement. POMC mRNA was measured by a solution hybridization S1 nuclease protection assay; beta-endorphin (beta-EP) and alpha-MSH were measured by RIA. In the first study 4 groups of ovariectomized (OVX) rats were treated with saline, haloperidol, E2 or E2 + pergolide. The mean POMC mRNA concentration in the MBH was 0.85 +/- 0.04 pg/microgram RNA in the saline group and decreased to 0.62 +/- 0.06 pg/microgram with haloperidol (p < 0.01). A similar decrease to 0.53 +/- 0.03 pg/microgram was seen with E2 (p < 0.01); pergolide however prevented the E2 induced decrease in POMC mRNA. In the second study ORCX rats received saline or haloperidol and sham-ORCX rats received saline or pergolide.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Obstetrics and Gynecology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
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D000818:Animals; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010479:Pergolide / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology
D018492:Dopamine Antagonists; D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D010479:Pergolide; D013739:Testosterone; D004958:Estradiol; D011333:Pro-Opiomelanocortin; D015719:Single-Strand Specific DNA and RNA Endonucleases; D006220:Haloperidol; D004298:Dopamine