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MARGARET A. SHUPNIK, ANNE KLIBANSKI, CHRISTOPHER LONGCOPE, E. CHESTER RIDGWAY, Catecholestrogen Regulation of Prolactin Synthesis in Pituitary Cell Culture, Endocrinology, Volume 117, Issue 3, 1 September 1985, Pages 939–946, https://doi.org/10.1210/endo-117-3-939
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Abstract
The 2-hydroxycatecholestrogens, 2-hydroxyestradiol [1,3,5-(10)estratriene-2,3,17β-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 10−8m 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 10−10m and 10−8m. At concentrations above 5 × 10−8m, however, both compounds decreased PRL levels until, at 10−6m 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 10−8m of either 17β-estradiol (E2), 2-OHE1, or 2-OHE2 resulted in 2- to 5-fold increases in translatable and hybridizable PRL mRNA. The addition of 10−7m E2 plus 10−8m 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 10−6m 2-OHE1 or 2-OHE2 was partially overcome by coincubation of cultures with E2. Thus, 2- OHE1 and 2-OHE2 at low concentrations (<10−8m) can act on the pituitary as E2 agonists to increase PRL synthesis but at high concentrations may act as inhibitors of PRL production. (Endocrinology117: 939–946, 1985)
