Multihormonal regulation of dehydroepiandrosterone sulfotransferase messenger ribonucleic acid levels in adult rat liver.
Hydroxysteroid sulfotransferases (DHEA ST) represent a family of enzymes that catalyze the conversion of dehydroepiandrosterone and other 3 beta-hydroxysteroids into more hydrophilic water-soluble sulfate conjugates. The present study was designed to investigate the regulation of hepatic DHEA ST expression by sex steroids and pituitary hormones, namely GH and PRL, in both male and female rats. DHEA ST mRNA levels were measured by dot blot hybridization using a 332-basepair fragment of rat DHEA ST (ST-20) cDNA as a probe. Hepatic DHEA ST mRNA levels were 2.8-fold higher in females than in males. A 15-day gonadectomy did not affect DHEA ST mRNA levels in the male liver; in females, a 35% decrease in DHEA ST mRNA levels compared with those in intact controls was observed. Administration of 17 beta-estradiol (E2; 1 microgram/kg, twice daily) alone had no effect on the accumulation of DHEA ST mRNA, but the same treatment completely reversed the marked inhibitory effect of dihydrotestosterone (DHT; 400 micrograms/kg, twice daily) on this parameter in both gonadectomized males and females. In female rats, 24-day hypophysectomy (HYPOX) decreased DHEA ST mRNA levels by 62%, whereas no change was detected in males. In HYPOX animals, treatment with E2 or DHT for 9 days starting 15 days after surgery had no effect on hepatic DHEA ST mRNA levels in rats of both sexes. In intact males, the presence of pituitary implants under the kidney capsule increased DHEA ST mRNA levels by 190% (above the control), which reached levels similar to those in intact females, whereas pituitary implants exerted no effect on this parameter in intact females. However, treatment of HYPOX rats with ovine PRL (oPRL; 4 mg/kg, twice daily) had no significant effect on the accumulation of DHEA ST mRNA in male and female animals. In HYPOX females, administration of rat GH (80 micrograms/kg, twice daily) had no effect on DHEA ST mRNA levels, whereas continuous infusion of rat GH (3.6 micrograms/h), using osmotic minipumps to mimic the female GH secretory pattern, increased this parameter by 290% (above the control value), thus completely reversing the effect of hypophysectomy. In HYPOX males, both modes of GH administration increased DHEA ST mRNA levels by 70-90% (above the control). The present study demonstrates that in both gonadectomized male and female rats, administration of E2 completely blocks the marked inhibitory effect of DHT on hepatic DHEA ST mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)
Labrie
Y
Y
Centre Hospitalier de L'Université Laval Research Center, Quebec, Canada.
Couët
J
J
Simard
J
J
Labrie
F
F
D000818:Animals; D001483:Base Sequence; D002369:Castration; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006728:Hormones / Q000502:physiology*; D007016:Hypophysectomy; D008099:Liver / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015238:Sulfotransferases / Q000235:genetics*
D006728:Hormones; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D004958:Estradiol; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase