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Published on: October 2, 2017
Aromatization is not required for androgen induced changes in proopiomelanocortin gene expression in the hypothalamus
1Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Abstract:
Testosterone regulation of POMC mRNA and peptide levels has been previously demonstrated in the medial basal hypothalamus (MBH) of the rat. Although both dihydrotestosterone (DHT) and estradiol are known to affect POMC peptide levels in the MBH, it is unclear if the effects of testosterone on POMC gene expression are due to conversion by aromatization to estradiol or due to independent androgen actions. We have therefore compared the effects of the nonaromatizable androgen DHT and estradiol on POMC gene expression and beta-endorphin (beta-EP) levels in the MBH of castrated male rats. We have also examined the effect of the dopamine agonist, pergolide, on POMC in the DHT and estradiol treated animals in light of previous studies in female rats. In the first study POMC mRNA in the MBH, as measured by a solution hybridization assay, was 0.85 +/- 0.07 pg/microgram RNA 3 weeks after castration and decreased to 0.64 +/- 0.07 pg and 0.65 +/- 0.07 pg in the DHT treated rats with and without pergolide (P < 0.05). In the second study the mean POMC mRNA concentration in the MBH was 0.95 +/- 0.10 pg/microgram RNA and decreased to 0.68 +/- 0.06 pg and 0.70 +/- 0.08 pg in the estradiol treated rats with and without pergolide (P < 0.05). In both studies significant changes in beta-EP peptide levels paralleled the changes in POMC mRNA levels. We conclude that both androgens and estrogens can affect POMC mRNA levels in the male rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study investigated how androgens and estrogens affect pro-opiomelanocortin (POMC) gene expression in the hypothalamus of male rats. Both dihydrotestosterone (DHT) and estradiol were found to decrease POMC mRNA and beta-endorphin levels.
Area of Science:
- Neuroendocrinology
- Molecular Endocrinology
Background:
- Testosterone influences pro-opiomelanocortin (POMC) mRNA and peptide levels in the medial basal hypothalamus (MBH).
- It remains unclear whether testosterone's effects are mediated by its conversion to estradiol or by direct androgen actions.
Purpose of the Study:
- To compare the effects of the non-aromatizable androgen dihydrotestosterone (DHT) and estradiol on POMC gene expression and beta-endorphin (beta-EP) levels in castrated male rats.
- To examine the influence of the dopamine agonist pergolide on POMC in DHT- and estradiol-treated rats.
Main Methods:
- Solution hybridization assay to measure POMC mRNA levels in the MBH of castrated male rats.
- Administration of DHT and estradiol, with and without pergolide.
- Measurement of beta-EP peptide levels.
Main Results:
- DHT treatment significantly decreased POMC mRNA levels in the MBH of castrated male rats.
- Estradiol treatment also significantly decreased POMC mRNA levels in the MBH.
- Changes in beta-EP peptide levels consistently paralleled the observed changes in POMC mRNA levels.
Conclusions:
- Both androgens (like DHT) and estrogens (like estradiol) can independently regulate POMC mRNA levels in the male rat MBH.
- These findings suggest distinct pathways for androgen and estrogenic regulation of POMC in the male hypothalamus.
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