Catecholestrogen regulation of prolactin synthesis in pituitary cell culture.
The 2-hydroxycatecholestrogens, 2-hydroxyestradiol [1,3,5-(10)estratriene-2,3,17 beta-triol] (2-OHE2) and 2-hydroxyestrone [2,3-dihydroxy-1,3,5-(10)-estratriene-17-one] (2-OHE1) were tested for their ability to alter PRL production and PRL messenger RNA (mRNA) levels in rat pituitary cell cultures. Treatment of cells with 10(-8) M 2-OHE1 or 2-OHE2 resulted in increased PRL secretion at 24 and 48 h (to 167% and 211% of control, respectively), but not at 4 h. Metabolism studies of radioactive 2-OHE1 and 2-OHE2 in parallel cultures demonstrated that the major metabolite at all times for either compound was the 2-methoxy derivative. After 24 h of treatment, nearly 40% of each compound was the original catecholestrogen, and at no time was there any detectable conversion to estradiol or estrone. Treatment of pituitary cells for 48 h with increasing concentrations of 2-OHE1 or 2-OHE2 resulted in a biphasic PRL dose response. PRL secretion was increased 3.6-fold for 2-OHE2 and 2.4-fold for 2-OHE1 between 10(-10) M and 10(-8) M. At concentrations above 5 X 10(-8) M, however, both compounds decreased PRL levels until, at 10(-6) M 2-OHE1 or 2-OHE2, PRL levels were 40-70% of control. Changes in PRL mRNA levels paralleled those of secretion. Treatment of pituitary cells with 10(-8) M of either 17 beta-estradiol (E2), 2-OHE1, or 2-OHE2 resulted in 2- to 5-fold increases in translatable and hybridizable PRL mRNA. The addition of 10(-7) M E2 plus 10(-8) M 2-OHE1 or 2-OHE2 resulted in PRL secretion and PRL mRNA levels equal to those resulting from E2 stimulation alone. The inhibition in PRL secretion and PRL mRNA levels caused by 10(-6) M 2-OHE1 or 2-OHE2 was partially overcome by coincubation of cultures with E2. Thus, 2-OHE1 and 2-OHE2 at low concentrations (less than 10(-8) M) can act on the pituitary as E2 agonists to increase PRL synthesis but at high concentrations may act as inhibitors of PRL production.
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives*; D005260:Female; D006894:Hydroxyestrones / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D006894:Hydroxyestrones; D012333:RNA, Messenger; D004970:Estrone; D004958:Estradiol; D011388:Prolactin; C001390:2-hydroxyestradiol; C024980:2-hydroxyestrone