Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats

S. Kono, D. D. Brandon, G. R. Merriam, Donald (Lynn) Loriaux, M. B. Lipsett

Research output: Contribution to journalArticle

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Abstract

2-Hydroxyestrone (2-OHE 1) has much lower uterotropic potency than might be predicted from its uterine estrogen receptor affinity. 2-OHE 1 displaces saturably bound [ 3H]estradiol from rat uterine cytosol with a competitive inhibition constant of 8.6 nM, while the dissociation constant for 17β-estradiol (E 2) is 0.42 nM. From this ratio of binding affinities, one would expect some agonist or antagonist activity of 2-OHE 1 to be apparent at doses roughly 20-50 times the minimum effective dose of E 2. Instead, at doses of 2-OHE 1 1000 times an effective dose of E 2, no uterotropic effect was observed. When 2-OHE 1 was injected together with E 2 at dose ratios of 500:1, there was no antagonism of the effect of E 2. To examine this discrepancy, the plasma MCRs (MCR(p)s) of E 2 and 2-OHE 1 were determined by continuous infusion techniques. Plasma concentrations of 2-OHE 1 and E 2 during control and infusion periods were measured by RIAs. The MCR(p) of 2-OHE 1 averaged 50,000 ml/h, more than 100 times that of E 2 (~400 ml/h). The extraordinarily high MCR(p) of 2-OHE 1 may explain the failure to observe any biological effects of this catechol estrogen, even at high blood compartment, should be considered in handling blood samples for RIA and in devising studies of the actions of catechol estrogens.

Original languageEnglish (US)
Pages (from-to)40-43
Number of pages4
JournalEndocrinology
Volume108
Issue number1
StatePublished - 1981
Externally publishedYes

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Catechol Estrogens
Metabolic Clearance Rate
Estradiol
Estrogen Receptors
Cytosol
2-hydroxyestrone

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Kono, S., Brandon, D. D., Merriam, G. R., Loriaux, D. L., & Lipsett, M. B. (1981). Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats. Endocrinology, 108(1), 40-43.

Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats. / Kono, S.; Brandon, D. D.; Merriam, G. R.; Loriaux, Donald (Lynn); Lipsett, M. B.

In: Endocrinology, Vol. 108, No. 1, 1981, p. 40-43.

Research output: Contribution to journalArticle

Kono, S, Brandon, DD, Merriam, GR, Loriaux, DL & Lipsett, MB 1981, 'Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats', Endocrinology, vol. 108, no. 1, pp. 40-43.
Kono, S. ; Brandon, D. D. ; Merriam, G. R. ; Loriaux, Donald (Lynn) ; Lipsett, M. B. / Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats. In: Endocrinology. 1981 ; Vol. 108, No. 1. pp. 40-43.
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N2 - 2-Hydroxyestrone (2-OHE 1) has much lower uterotropic potency than might be predicted from its uterine estrogen receptor affinity. 2-OHE 1 displaces saturably bound [ 3H]estradiol from rat uterine cytosol with a competitive inhibition constant of 8.6 nM, while the dissociation constant for 17β-estradiol (E 2) is 0.42 nM. From this ratio of binding affinities, one would expect some agonist or antagonist activity of 2-OHE 1 to be apparent at doses roughly 20-50 times the minimum effective dose of E 2. Instead, at doses of 2-OHE 1 1000 times an effective dose of E 2, no uterotropic effect was observed. When 2-OHE 1 was injected together with E 2 at dose ratios of 500:1, there was no antagonism of the effect of E 2. To examine this discrepancy, the plasma MCRs (MCR(p)s) of E 2 and 2-OHE 1 were determined by continuous infusion techniques. Plasma concentrations of 2-OHE 1 and E 2 during control and infusion periods were measured by RIAs. The MCR(p) of 2-OHE 1 averaged 50,000 ml/h, more than 100 times that of E 2 (~400 ml/h). The extraordinarily high MCR(p) of 2-OHE 1 may explain the failure to observe any biological effects of this catechol estrogen, even at high blood compartment, should be considered in handling blood samples for RIA and in devising studies of the actions of catechol estrogens.

AB - 2-Hydroxyestrone (2-OHE 1) has much lower uterotropic potency than might be predicted from its uterine estrogen receptor affinity. 2-OHE 1 displaces saturably bound [ 3H]estradiol from rat uterine cytosol with a competitive inhibition constant of 8.6 nM, while the dissociation constant for 17β-estradiol (E 2) is 0.42 nM. From this ratio of binding affinities, one would expect some agonist or antagonist activity of 2-OHE 1 to be apparent at doses roughly 20-50 times the minimum effective dose of E 2. Instead, at doses of 2-OHE 1 1000 times an effective dose of E 2, no uterotropic effect was observed. When 2-OHE 1 was injected together with E 2 at dose ratios of 500:1, there was no antagonism of the effect of E 2. To examine this discrepancy, the plasma MCRs (MCR(p)s) of E 2 and 2-OHE 1 were determined by continuous infusion techniques. Plasma concentrations of 2-OHE 1 and E 2 during control and infusion periods were measured by RIAs. The MCR(p) of 2-OHE 1 averaged 50,000 ml/h, more than 100 times that of E 2 (~400 ml/h). The extraordinarily high MCR(p) of 2-OHE 1 may explain the failure to observe any biological effects of this catechol estrogen, even at high blood compartment, should be considered in handling blood samples for RIA and in devising studies of the actions of catechol estrogens.

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