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 SI nuclease protection assay; β-endorphin (β-EP) and α-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/µg RNA in the saline group and decreased to 0.62 ± 0.06 pg/µg with haloperidol (p < 0.01). A similar decrease to 0.53 ± 0.03 pg/µg 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. The mean POMC mRNA level was 1.05 ± 0.13 pg/ µg RNA in the ORCX rats and decreased to 0.69 ± 0.09 after haloperidol (p < 0.05), a level similar to that noted in the intact group. However, POMC mRNA levels in the intact pergolide treated group were not different from the intact untreated group. In the third study, ORCX rats were treated with T or T + pergolide. POMC mRNA again fell significantly in the T-treated rats; a similar decline was seen after T + pergolide treatment. Thus in contrast to the female rats, pergolide did not block the sex steroid induced suppression of POMC mRNA in the MBH. In all 3 studies the concentrations of β-EP and α-MSH in the MBH were lower in the intact or steroid replaced rats compared to castrated unreplaced rats; neither haloperidol or pergolide had any significant effect on β-EP or α-MSH levels. Thus dopamine antagonism suppressed POMC mRNA levels in the MBH of chronically castrated male and female rats and the dopamine agonist pergolide stimulated POMC mRNA levels in the MBH of E2-replaced female rats. We conclude that dopamine stimulates POMC genes expression in the MBH and suggest that the changes in dopamine tone that occur with castration and sex steroid replacement may mediate some of the parallel changes in POMC that occur under these conditions.

Keywords:
Proopiomelanocortin, β-Endorphin, α-MSH, Dopamine, Estradiol, Testosterone, Hypothalamus
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© 1993 S. Karger AG, Basel
1993
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