Effect of hypophysectomy and hormone replacement on hormone receptor levels and the growth of 7, 12 dimethylbenz(a)anthracene-induced mammary tumors in the rat

Bahauddin M. Arafah, Andrea Manni, Olof H. Pearson

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Abstract

17β-Estradiol (E2) and PRL were administered after hypophysectomy (hypox), either alone or in combination, to rats bearing 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in order to clarify the individual role of these hormones on tumor growth and estrogen (ER), progesterone (PgR), and PRL (PRLR) receptor content. Of 180 tumors, 150 (83%) regressed, 5 (3%) remained stable, and 25 (14%) continued to grow after hypox. The administration of ovine PRL (oPRL) after hypox, reactivated the growth of regressing mammary tumors, whereas E2 did not. No synergism between E2 and oPRL on tumor growth was observed. These hormones had no discernible effect on the growth rate of stable and growing tumors. PgR in hormone-dependent tumors declined from 69.9 ± 15.9 to 15 ± 8.4 fmol/mg (P < 0.005) 6 days after hypox and to 4.5 ± 4.2 fmol/mg cytosol protein (P < 0.005) 16 days after hypox. E2 administration (5 μg/day), begun 6 days after hypox and continued for 9 days, restored PgR to control levels. oPRL administration (20 IU/day) for 11 days, starting 6 days after hypox, had no effect on the PgR level. The ER level did not change in 6 days (25.5 ± 3 vs. 24.5 ± 4.2 fmol/mg) but declined to 9.2 ± 2.3 fmol/mg (P < 0.0005) in hormone-dependent tumors 16 days after hypox. The administration of either E2 or oPRL prevented the fall in ER noted in the untreated group. The PRLR level in hormone-dependent tumors declined slowly after hypox from 41.8 ± 6.1 to 35.4 ± 8.8 fmol/mg in 6 days (P = NS) and to 11.8 ± 3.4 fmol/mg (P < 0.005) in 16 days. The dministration of either E2 or PRL prevented the fall in PRLR noted in the untreated group. There was no synergism between E2 and PRL in their effects on ER, PgR, and PRLR levels in mammary tumors. ER, PgR, and PRLR were present at similar levels in hormone-independent tumors, and thus are not predictive of hormone dependency. PgR synthesis was estrogen dependent in the hormone-independent tumors. The changes in ER after hypox and PRL administration showed trends similar to those in the hormone-dependent tumors, but the differences were not statistically significant. We conclude that PRL is the predominant hormone controlling the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in rats. E2 administration induces PgR synthesis in the tumors without influencing tumor growth. The administration of either E2 or PRL after hypox can maintain both ER and PRLR levels. Thus, E2 might play an indirect role in tumor growth by maintaining PRLR. No synergism between E2 and PRL was seen in their effects on tumor growth or ER, PgR, and PRLR levels. The presence of these hormone receptors does not predict hormone responsiveness in this tumor model.

Original languageEnglish (US)
Pages (from-to)1364-1369
Number of pages6
JournalEndocrinology
Volume107
Issue number5
DOIs
StatePublished - Jan 1 1980

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Somatotropin Receptors
Hypophysectomy
Hormones
Breast Neoplasms
Progesterone
Estrogens
Neoplasms
Growth
Sheep
anthracene
olifen
Prolactin Receptors

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

@article{37f6a118327742268c6716e4c9d1f65b,
title = "Effect of hypophysectomy and hormone replacement on hormone receptor levels and the growth of 7, 12 dimethylbenz(a)anthracene-induced mammary tumors in the rat",
abstract = "17β-Estradiol (E2) and PRL were administered after hypophysectomy (hypox), either alone or in combination, to rats bearing 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in order to clarify the individual role of these hormones on tumor growth and estrogen (ER), progesterone (PgR), and PRL (PRLR) receptor content. Of 180 tumors, 150 (83{\%}) regressed, 5 (3{\%}) remained stable, and 25 (14{\%}) continued to grow after hypox. The administration of ovine PRL (oPRL) after hypox, reactivated the growth of regressing mammary tumors, whereas E2 did not. No synergism between E2 and oPRL on tumor growth was observed. These hormones had no discernible effect on the growth rate of stable and growing tumors. PgR in hormone-dependent tumors declined from 69.9 ± 15.9 to 15 ± 8.4 fmol/mg (P < 0.005) 6 days after hypox and to 4.5 ± 4.2 fmol/mg cytosol protein (P < 0.005) 16 days after hypox. E2 administration (5 μg/day), begun 6 days after hypox and continued for 9 days, restored PgR to control levels. oPRL administration (20 IU/day) for 11 days, starting 6 days after hypox, had no effect on the PgR level. The ER level did not change in 6 days (25.5 ± 3 vs. 24.5 ± 4.2 fmol/mg) but declined to 9.2 ± 2.3 fmol/mg (P < 0.0005) in hormone-dependent tumors 16 days after hypox. The administration of either E2 or oPRL prevented the fall in ER noted in the untreated group. The PRLR level in hormone-dependent tumors declined slowly after hypox from 41.8 ± 6.1 to 35.4 ± 8.8 fmol/mg in 6 days (P = NS) and to 11.8 ± 3.4 fmol/mg (P < 0.005) in 16 days. The dministration of either E2 or PRL prevented the fall in PRLR noted in the untreated group. There was no synergism between E2 and PRL in their effects on ER, PgR, and PRLR levels in mammary tumors. ER, PgR, and PRLR were present at similar levels in hormone-independent tumors, and thus are not predictive of hormone dependency. PgR synthesis was estrogen dependent in the hormone-independent tumors. The changes in ER after hypox and PRL administration showed trends similar to those in the hormone-dependent tumors, but the differences were not statistically significant. We conclude that PRL is the predominant hormone controlling the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in rats. E2 administration induces PgR synthesis in the tumors without influencing tumor growth. The administration of either E2 or PRL after hypox can maintain both ER and PRLR levels. Thus, E2 might play an indirect role in tumor growth by maintaining PRLR. No synergism between E2 and PRL was seen in their effects on tumor growth or ER, PgR, and PRLR levels. The presence of these hormone receptors does not predict hormone responsiveness in this tumor model.",
author = "Arafah, {Bahauddin M.} and Andrea Manni and Pearson, {Olof H.}",
year = "1980",
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Effect of hypophysectomy and hormone replacement on hormone receptor levels and the growth of 7, 12 dimethylbenz(a)anthracene-induced mammary tumors in the rat. / Arafah, Bahauddin M.; Manni, Andrea; Pearson, Olof H.

In: Endocrinology, Vol. 107, No. 5, 01.01.1980, p. 1364-1369.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of hypophysectomy and hormone replacement on hormone receptor levels and the growth of 7, 12 dimethylbenz(a)anthracene-induced mammary tumors in the rat

AU - Arafah, Bahauddin M.

AU - Manni, Andrea

AU - Pearson, Olof H.

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Y1 - 1980/1/1

N2 - 17β-Estradiol (E2) and PRL were administered after hypophysectomy (hypox), either alone or in combination, to rats bearing 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in order to clarify the individual role of these hormones on tumor growth and estrogen (ER), progesterone (PgR), and PRL (PRLR) receptor content. Of 180 tumors, 150 (83%) regressed, 5 (3%) remained stable, and 25 (14%) continued to grow after hypox. The administration of ovine PRL (oPRL) after hypox, reactivated the growth of regressing mammary tumors, whereas E2 did not. No synergism between E2 and oPRL on tumor growth was observed. These hormones had no discernible effect on the growth rate of stable and growing tumors. PgR in hormone-dependent tumors declined from 69.9 ± 15.9 to 15 ± 8.4 fmol/mg (P < 0.005) 6 days after hypox and to 4.5 ± 4.2 fmol/mg cytosol protein (P < 0.005) 16 days after hypox. E2 administration (5 μg/day), begun 6 days after hypox and continued for 9 days, restored PgR to control levels. oPRL administration (20 IU/day) for 11 days, starting 6 days after hypox, had no effect on the PgR level. The ER level did not change in 6 days (25.5 ± 3 vs. 24.5 ± 4.2 fmol/mg) but declined to 9.2 ± 2.3 fmol/mg (P < 0.0005) in hormone-dependent tumors 16 days after hypox. The administration of either E2 or oPRL prevented the fall in ER noted in the untreated group. The PRLR level in hormone-dependent tumors declined slowly after hypox from 41.8 ± 6.1 to 35.4 ± 8.8 fmol/mg in 6 days (P = NS) and to 11.8 ± 3.4 fmol/mg (P < 0.005) in 16 days. The dministration of either E2 or PRL prevented the fall in PRLR noted in the untreated group. There was no synergism between E2 and PRL in their effects on ER, PgR, and PRLR levels in mammary tumors. ER, PgR, and PRLR were present at similar levels in hormone-independent tumors, and thus are not predictive of hormone dependency. PgR synthesis was estrogen dependent in the hormone-independent tumors. The changes in ER after hypox and PRL administration showed trends similar to those in the hormone-dependent tumors, but the differences were not statistically significant. We conclude that PRL is the predominant hormone controlling the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in rats. E2 administration induces PgR synthesis in the tumors without influencing tumor growth. The administration of either E2 or PRL after hypox can maintain both ER and PRLR levels. Thus, E2 might play an indirect role in tumor growth by maintaining PRLR. No synergism between E2 and PRL was seen in their effects on tumor growth or ER, PgR, and PRLR levels. The presence of these hormone receptors does not predict hormone responsiveness in this tumor model.

AB - 17β-Estradiol (E2) and PRL were administered after hypophysectomy (hypox), either alone or in combination, to rats bearing 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in order to clarify the individual role of these hormones on tumor growth and estrogen (ER), progesterone (PgR), and PRL (PRLR) receptor content. Of 180 tumors, 150 (83%) regressed, 5 (3%) remained stable, and 25 (14%) continued to grow after hypox. The administration of ovine PRL (oPRL) after hypox, reactivated the growth of regressing mammary tumors, whereas E2 did not. No synergism between E2 and oPRL on tumor growth was observed. These hormones had no discernible effect on the growth rate of stable and growing tumors. PgR in hormone-dependent tumors declined from 69.9 ± 15.9 to 15 ± 8.4 fmol/mg (P < 0.005) 6 days after hypox and to 4.5 ± 4.2 fmol/mg cytosol protein (P < 0.005) 16 days after hypox. E2 administration (5 μg/day), begun 6 days after hypox and continued for 9 days, restored PgR to control levels. oPRL administration (20 IU/day) for 11 days, starting 6 days after hypox, had no effect on the PgR level. The ER level did not change in 6 days (25.5 ± 3 vs. 24.5 ± 4.2 fmol/mg) but declined to 9.2 ± 2.3 fmol/mg (P < 0.0005) in hormone-dependent tumors 16 days after hypox. The administration of either E2 or oPRL prevented the fall in ER noted in the untreated group. The PRLR level in hormone-dependent tumors declined slowly after hypox from 41.8 ± 6.1 to 35.4 ± 8.8 fmol/mg in 6 days (P = NS) and to 11.8 ± 3.4 fmol/mg (P < 0.005) in 16 days. The dministration of either E2 or PRL prevented the fall in PRLR noted in the untreated group. There was no synergism between E2 and PRL in their effects on ER, PgR, and PRLR levels in mammary tumors. ER, PgR, and PRLR were present at similar levels in hormone-independent tumors, and thus are not predictive of hormone dependency. PgR synthesis was estrogen dependent in the hormone-independent tumors. The changes in ER after hypox and PRL administration showed trends similar to those in the hormone-dependent tumors, but the differences were not statistically significant. We conclude that PRL is the predominant hormone controlling the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in rats. E2 administration induces PgR synthesis in the tumors without influencing tumor growth. The administration of either E2 or PRL after hypox can maintain both ER and PRLR levels. Thus, E2 might play an indirect role in tumor growth by maintaining PRLR. No synergism between E2 and PRL was seen in their effects on tumor growth or ER, PgR, and PRLR levels. The presence of these hormone receptors does not predict hormone responsiveness in this tumor model.

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