Effects of dehydroepiandrosterone (DHEA) on pituitary prolactin and arcuate nucleus neuron tyrosine hydroxylase mRNA levels in the rat.
It is well documented that dehydroepiandrosterone (DHEA), an adrenal androgen, is converted into potent androgens and/or estrogens in peripheral tissues. Since sex steroids are involved in the regulation of prolactin (PRL) secretion, we have studied the effect of DHEA administration on PRL mRNA levels in both adult male and female rats. Since tuberoinfundibular dopaminergic (TIDA) neurons are involved in the negative regulation of PRL, we have also evaluated the effects of DHEA on the genetic expression of tyrosine hydroxylase (TH), the limiting enzyme in catecholamine biosynthesis in TIDA neurons. Sham-operated and castrated animals of both sexes received during 2 days DHEA at the dose of 6 mg/kg/day, starting on the first day after castration. PRL and TH mRNA levels were measured by quantitative in situ hybridization. In the male rat, orchiectomy performed 3 days earlier did not modify PRL mRNA levels. DHEA administration increased the hybridization signal in both sham-operated and orchiectomized animals. In the female, ovariectomy decreased PRL mRNA levels and, as observed in the male, DHEA treatment induced an increase in the hybridization signal in both control and ovariectomized rats. In TIDA neurons, castration increased TH mRNA levels as evaluated by number of grains over labelled neurons and the number of TH-labelled cells per section in both male and female animals. In both sham-operated male rats and orchiectomized animals, DHEA decreased the hybridization signal. In the female, DHEA administration completely prevented the increase in TH mRNA levels due to ovariectomy. In sham-operated female rats, the treatment had no effect. These data clearly indicate that in both male and female rats DHEA exerts an estrogenic influence on both PRL and TH gene expression. Although these in vivo experiments do not allow to establish whether the stimulation of PRL gene expression is due to an action of the steroid on the pituitary or at the hypothalamic level or alternatively at both sites, it is likely that one of the mechanisms of action of DHEA might be related to a decrease in dopamine release following a depression of TIDA neuron activity.
Garcia de Yebenes
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E
MRC Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
Hong
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M
Pelletier
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G
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D001345:Autoradiography; D015342:DNA Probes; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013462:Sulfur Radioisotopes; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
D015342:DNA Probes; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D003687:Dehydroepiandrosterone; D011388:Prolactin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine