Comparative dynamic studies on the biological responses to estriol and 17β-estradiol in the fetal uterus of guinea pig: Relationship to circulating estrogen concentrations

A. Gulino, C. Sumida, C. Gelly, N. Giambiagi, J. R. Pasqualini

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Abstract

This study compares the kinetics of biological responses to estriol (E 3) and 17β-estradiol (E 2) treatment (uterotrophic effect and uterine progesterone receptor stimulation) in the fetal uterus of guinea pig. A single sc administration of 1 mg/kg of E 2 or E 3 to pregnant guinea pigs provokes a slight early uterotrophic effect in the fetus after 3 h for E 3 and 6 h for E 2 (26% increase for both in relation to controls) and a late uterotrophic effect that is maximal 2 days after treatment with both E 2 and E 3 (80% increase). This second phase of the uterotrophic effect is of shorter duration in E 3-treated animals (return to control values after 7 days) than in E 2-treated animals (maintain maximal values 7 days after treatment). The same treatment provokes a stimulation of uterine progesterone receptor that is detectable sooner for E 3-treated (3 h) than for E 2-treated animals (6 h) and that is maximal between 15 h and 24 h after hormone administration (10-fold increase in relation to controls). The maximal uterine wet weight and concentration of uterine progesterone receptor attained after a single injection of either E 3 or E 2 are the same as those found after three daily injections of either hormone. This uterotrophic effect was not accompanied by an increase in DNA content. Both E 3 and E 2 are capable of translocating estrogen receptor from the cytosol into the nucleus, but E 3 causes this transfer more rapidly (1 h) than E 2 (3-6 h). After translocation, E 3-receptor complex is rapidly released by the nucleus, but the levels still remain significantly higher than control values up to 24 h. In contrast, low levels of E 2-receptor complex remain in the nucleus for at least 7 days after a single administration of E 2. The appearance of the two biological responses is related to the time of estrogen receptor translocation by both E 3 and E 2, whereas only the prolonged uterotrophic effect can be correlated with the persistence of estrogen receptor in the nucleus, since a dissociation of the disappearance curves of the two responses is observed after E 2 administration. The similar responses to E 3 and E 2, as well as their different kinetic patterns, can be explained by the concentrations of the hormones in the fetal plasma and by their relatively slow clearance from the circulation: although both hormones remain at sufficiently high levels for enough time to provoke the maximal late uterotrophic effect, the E 3 levels between 3 and 7 days after treatment are not sufficient to maintain the E 3-receptor complex in the nucleus. Thus, in the fetal guinea pig uterus, E 3 when maintained at persistent and high levels elicits estrogenic responses similar to E 2.

Original languageEnglish
Pages (from-to)748-756
Number of pages9
JournalEndocrinology
Volume109
Issue number3
Publication statusPublished - 1981

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Estriol
Uterus
Estradiol
Estrogens
Guinea Pigs
Progesterone Receptors
Estrogen Receptors
Hormones
Therapeutics
Injections
Cytosol
Fetus
Weights and Measures
DNA

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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Comparative dynamic studies on the biological responses to estriol and 17β-estradiol in the fetal uterus of guinea pig : Relationship to circulating estrogen concentrations. / Gulino, A.; Sumida, C.; Gelly, C.; Giambiagi, N.; Pasqualini, J. R.

In: Endocrinology, Vol. 109, No. 3, 1981, p. 748-756.

Research output: Contribution to journalArticle

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title = "Comparative dynamic studies on the biological responses to estriol and 17β-estradiol in the fetal uterus of guinea pig: Relationship to circulating estrogen concentrations",
abstract = "This study compares the kinetics of biological responses to estriol (E 3) and 17β-estradiol (E 2) treatment (uterotrophic effect and uterine progesterone receptor stimulation) in the fetal uterus of guinea pig. A single sc administration of 1 mg/kg of E 2 or E 3 to pregnant guinea pigs provokes a slight early uterotrophic effect in the fetus after 3 h for E 3 and 6 h for E 2 (26{\%} increase for both in relation to controls) and a late uterotrophic effect that is maximal 2 days after treatment with both E 2 and E 3 (80{\%} increase). This second phase of the uterotrophic effect is of shorter duration in E 3-treated animals (return to control values after 7 days) than in E 2-treated animals (maintain maximal values 7 days after treatment). The same treatment provokes a stimulation of uterine progesterone receptor that is detectable sooner for E 3-treated (3 h) than for E 2-treated animals (6 h) and that is maximal between 15 h and 24 h after hormone administration (10-fold increase in relation to controls). The maximal uterine wet weight and concentration of uterine progesterone receptor attained after a single injection of either E 3 or E 2 are the same as those found after three daily injections of either hormone. This uterotrophic effect was not accompanied by an increase in DNA content. Both E 3 and E 2 are capable of translocating estrogen receptor from the cytosol into the nucleus, but E 3 causes this transfer more rapidly (1 h) than E 2 (3-6 h). After translocation, E 3-receptor complex is rapidly released by the nucleus, but the levels still remain significantly higher than control values up to 24 h. In contrast, low levels of E 2-receptor complex remain in the nucleus for at least 7 days after a single administration of E 2. The appearance of the two biological responses is related to the time of estrogen receptor translocation by both E 3 and E 2, whereas only the prolonged uterotrophic effect can be correlated with the persistence of estrogen receptor in the nucleus, since a dissociation of the disappearance curves of the two responses is observed after E 2 administration. The similar responses to E 3 and E 2, as well as their different kinetic patterns, can be explained by the concentrations of the hormones in the fetal plasma and by their relatively slow clearance from the circulation: although both hormones remain at sufficiently high levels for enough time to provoke the maximal late uterotrophic effect, the E 3 levels between 3 and 7 days after treatment are not sufficient to maintain the E 3-receptor complex in the nucleus. Thus, in the fetal guinea pig uterus, E 3 when maintained at persistent and high levels elicits estrogenic responses similar to E 2.",
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AU - Sumida, C.

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AU - Giambiagi, N.

AU - Pasqualini, J. R.

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N2 - This study compares the kinetics of biological responses to estriol (E 3) and 17β-estradiol (E 2) treatment (uterotrophic effect and uterine progesterone receptor stimulation) in the fetal uterus of guinea pig. A single sc administration of 1 mg/kg of E 2 or E 3 to pregnant guinea pigs provokes a slight early uterotrophic effect in the fetus after 3 h for E 3 and 6 h for E 2 (26% increase for both in relation to controls) and a late uterotrophic effect that is maximal 2 days after treatment with both E 2 and E 3 (80% increase). This second phase of the uterotrophic effect is of shorter duration in E 3-treated animals (return to control values after 7 days) than in E 2-treated animals (maintain maximal values 7 days after treatment). The same treatment provokes a stimulation of uterine progesterone receptor that is detectable sooner for E 3-treated (3 h) than for E 2-treated animals (6 h) and that is maximal between 15 h and 24 h after hormone administration (10-fold increase in relation to controls). The maximal uterine wet weight and concentration of uterine progesterone receptor attained after a single injection of either E 3 or E 2 are the same as those found after three daily injections of either hormone. This uterotrophic effect was not accompanied by an increase in DNA content. Both E 3 and E 2 are capable of translocating estrogen receptor from the cytosol into the nucleus, but E 3 causes this transfer more rapidly (1 h) than E 2 (3-6 h). After translocation, E 3-receptor complex is rapidly released by the nucleus, but the levels still remain significantly higher than control values up to 24 h. In contrast, low levels of E 2-receptor complex remain in the nucleus for at least 7 days after a single administration of E 2. The appearance of the two biological responses is related to the time of estrogen receptor translocation by both E 3 and E 2, whereas only the prolonged uterotrophic effect can be correlated with the persistence of estrogen receptor in the nucleus, since a dissociation of the disappearance curves of the two responses is observed after E 2 administration. The similar responses to E 3 and E 2, as well as their different kinetic patterns, can be explained by the concentrations of the hormones in the fetal plasma and by their relatively slow clearance from the circulation: although both hormones remain at sufficiently high levels for enough time to provoke the maximal late uterotrophic effect, the E 3 levels between 3 and 7 days after treatment are not sufficient to maintain the E 3-receptor complex in the nucleus. Thus, in the fetal guinea pig uterus, E 3 when maintained at persistent and high levels elicits estrogenic responses similar to E 2.

AB - This study compares the kinetics of biological responses to estriol (E 3) and 17β-estradiol (E 2) treatment (uterotrophic effect and uterine progesterone receptor stimulation) in the fetal uterus of guinea pig. A single sc administration of 1 mg/kg of E 2 or E 3 to pregnant guinea pigs provokes a slight early uterotrophic effect in the fetus after 3 h for E 3 and 6 h for E 2 (26% increase for both in relation to controls) and a late uterotrophic effect that is maximal 2 days after treatment with both E 2 and E 3 (80% increase). This second phase of the uterotrophic effect is of shorter duration in E 3-treated animals (return to control values after 7 days) than in E 2-treated animals (maintain maximal values 7 days after treatment). The same treatment provokes a stimulation of uterine progesterone receptor that is detectable sooner for E 3-treated (3 h) than for E 2-treated animals (6 h) and that is maximal between 15 h and 24 h after hormone administration (10-fold increase in relation to controls). The maximal uterine wet weight and concentration of uterine progesterone receptor attained after a single injection of either E 3 or E 2 are the same as those found after three daily injections of either hormone. This uterotrophic effect was not accompanied by an increase in DNA content. Both E 3 and E 2 are capable of translocating estrogen receptor from the cytosol into the nucleus, but E 3 causes this transfer more rapidly (1 h) than E 2 (3-6 h). After translocation, E 3-receptor complex is rapidly released by the nucleus, but the levels still remain significantly higher than control values up to 24 h. In contrast, low levels of E 2-receptor complex remain in the nucleus for at least 7 days after a single administration of E 2. The appearance of the two biological responses is related to the time of estrogen receptor translocation by both E 3 and E 2, whereas only the prolonged uterotrophic effect can be correlated with the persistence of estrogen receptor in the nucleus, since a dissociation of the disappearance curves of the two responses is observed after E 2 administration. The similar responses to E 3 and E 2, as well as their different kinetic patterns, can be explained by the concentrations of the hormones in the fetal plasma and by their relatively slow clearance from the circulation: although both hormones remain at sufficiently high levels for enough time to provoke the maximal late uterotrophic effect, the E 3 levels between 3 and 7 days after treatment are not sufficient to maintain the E 3-receptor complex in the nucleus. Thus, in the fetal guinea pig uterus, E 3 when maintained at persistent and high levels elicits estrogenic responses similar to E 2.

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