Psychosocial Stress Exposure Disrupts Mammary Gland Development

Marianna B. Johnson, Joscelyn N. Hoffmann, Hannah M. You, Ricardo R. Lastra, Sully Fernandez, Jordan W. Strober, Ahmad B. Allaw, Matthew J. Brady, Suzanne D. Conzen, Martha K. McClintock

Research output: Contribution to journalArticle

Abstract

Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8–25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats. We then demonstrate that social isolation increased stress reactivity to everyday stressors, resulting in downregulation of glucocorticoid receptor (GR) expression in the MG epithelium. Surprisingly, given that chemical carcinogens increase MG cancer risk by preventing normal terminal end bud (TEB) differentiation, chronic isolation stress did not alter TEBs. Instead, isolation blunted MG growth and alveolobular differentiation and reduced epithelial cell proliferation in these structures. Social isolation also enhanced corpora luteal progesterone at all ages but reduced estrogenization only in early adulthood, a pattern that precludes modulated ovarian function as a sufficient mechanism for the effects of isolation on MG development. This longitudinal study of natural variation provides an integrated view of MG development and the importance of increased GR activation in nulliparous ductal growth and alveolobular differentiation. Thus, social isolation and its physiological sequelae disrupt MG growth and differentiation and suggest a contribution of stress exposure during puberty and young adulthood to the previously observed increase in invasive MG cancer observed in chronically socially-isolated adult Sprague-Dawley rats.

Original languageEnglish (US)
Pages (from-to)59-73
Number of pages15
JournalJournal of mammary gland biology and neoplasia
Volume23
Issue number1-2
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

Fingerprint

Human Mammary Glands
Social Isolation
Breast Neoplasms
Glucocorticoid Receptors
Puberty
Sprague Dawley Rats
Longitudinal Studies
Growth
Corpus Luteum
Environmental Exposure
Carcinogens
Progesterone
Down-Regulation
Epithelium
Epithelial Cells
Cell Proliferation

Keywords

  • Alveolobular development
  • Mammary gland
  • Puberty
  • Stress
  • Terminal end buds
  • Young adulthood

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Johnson, M. B., Hoffmann, J. N., You, H. M., Lastra, R. R., Fernandez, S., Strober, J. W., ... McClintock, M. K. (2018). Psychosocial Stress Exposure Disrupts Mammary Gland Development. Journal of mammary gland biology and neoplasia, 23(1-2), 59-73. https://doi.org/10.1007/s10911-018-9392-4

Psychosocial Stress Exposure Disrupts Mammary Gland Development. / Johnson, Marianna B.; Hoffmann, Joscelyn N.; You, Hannah M.; Lastra, Ricardo R.; Fernandez, Sully; Strober, Jordan W.; Allaw, Ahmad B.; Brady, Matthew J.; Conzen, Suzanne D.; McClintock, Martha K.

In: Journal of mammary gland biology and neoplasia, Vol. 23, No. 1-2, 01.06.2018, p. 59-73.

Research output: Contribution to journalArticle

Johnson, MB, Hoffmann, JN, You, HM, Lastra, RR, Fernandez, S, Strober, JW, Allaw, AB, Brady, MJ, Conzen, SD & McClintock, MK 2018, 'Psychosocial Stress Exposure Disrupts Mammary Gland Development', Journal of mammary gland biology and neoplasia, vol. 23, no. 1-2, pp. 59-73. https://doi.org/10.1007/s10911-018-9392-4
Johnson MB, Hoffmann JN, You HM, Lastra RR, Fernandez S, Strober JW et al. Psychosocial Stress Exposure Disrupts Mammary Gland Development. Journal of mammary gland biology and neoplasia. 2018 Jun 1;23(1-2):59-73. https://doi.org/10.1007/s10911-018-9392-4
Johnson, Marianna B. ; Hoffmann, Joscelyn N. ; You, Hannah M. ; Lastra, Ricardo R. ; Fernandez, Sully ; Strober, Jordan W. ; Allaw, Ahmad B. ; Brady, Matthew J. ; Conzen, Suzanne D. ; McClintock, Martha K. / Psychosocial Stress Exposure Disrupts Mammary Gland Development. In: Journal of mammary gland biology and neoplasia. 2018 ; Vol. 23, No. 1-2. pp. 59-73.
@article{4c779e1adbd34294821300486ccbe909,
title = "Psychosocial Stress Exposure Disrupts Mammary Gland Development",
abstract = "Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8–25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats. We then demonstrate that social isolation increased stress reactivity to everyday stressors, resulting in downregulation of glucocorticoid receptor (GR) expression in the MG epithelium. Surprisingly, given that chemical carcinogens increase MG cancer risk by preventing normal terminal end bud (TEB) differentiation, chronic isolation stress did not alter TEBs. Instead, isolation blunted MG growth and alveolobular differentiation and reduced epithelial cell proliferation in these structures. Social isolation also enhanced corpora luteal progesterone at all ages but reduced estrogenization only in early adulthood, a pattern that precludes modulated ovarian function as a sufficient mechanism for the effects of isolation on MG development. This longitudinal study of natural variation provides an integrated view of MG development and the importance of increased GR activation in nulliparous ductal growth and alveolobular differentiation. Thus, social isolation and its physiological sequelae disrupt MG growth and differentiation and suggest a contribution of stress exposure during puberty and young adulthood to the previously observed increase in invasive MG cancer observed in chronically socially-isolated adult Sprague-Dawley rats.",
keywords = "Alveolobular development, Mammary gland, Puberty, Stress, Terminal end buds, Young adulthood",
author = "Johnson, {Marianna B.} and Hoffmann, {Joscelyn N.} and You, {Hannah M.} and Lastra, {Ricardo R.} and Sully Fernandez and Strober, {Jordan W.} and Allaw, {Ahmad B.} and Brady, {Matthew J.} and Conzen, {Suzanne D.} and McClintock, {Martha K.}",
year = "2018",
month = "6",
day = "1",
doi = "10.1007/s10911-018-9392-4",
language = "English (US)",
volume = "23",
pages = "59--73",
journal = "Journal of Mammary Gland Biology and Neoplasia",
issn = "1083-3021",
publisher = "Springer New York",
number = "1-2",

}

TY - JOUR

T1 - Psychosocial Stress Exposure Disrupts Mammary Gland Development

AU - Johnson, Marianna B.

AU - Hoffmann, Joscelyn N.

AU - You, Hannah M.

AU - Lastra, Ricardo R.

AU - Fernandez, Sully

AU - Strober, Jordan W.

AU - Allaw, Ahmad B.

AU - Brady, Matthew J.

AU - Conzen, Suzanne D.

AU - McClintock, Martha K.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8–25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats. We then demonstrate that social isolation increased stress reactivity to everyday stressors, resulting in downregulation of glucocorticoid receptor (GR) expression in the MG epithelium. Surprisingly, given that chemical carcinogens increase MG cancer risk by preventing normal terminal end bud (TEB) differentiation, chronic isolation stress did not alter TEBs. Instead, isolation blunted MG growth and alveolobular differentiation and reduced epithelial cell proliferation in these structures. Social isolation also enhanced corpora luteal progesterone at all ages but reduced estrogenization only in early adulthood, a pattern that precludes modulated ovarian function as a sufficient mechanism for the effects of isolation on MG development. This longitudinal study of natural variation provides an integrated view of MG development and the importance of increased GR activation in nulliparous ductal growth and alveolobular differentiation. Thus, social isolation and its physiological sequelae disrupt MG growth and differentiation and suggest a contribution of stress exposure during puberty and young adulthood to the previously observed increase in invasive MG cancer observed in chronically socially-isolated adult Sprague-Dawley rats.

AB - Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8–25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats. We then demonstrate that social isolation increased stress reactivity to everyday stressors, resulting in downregulation of glucocorticoid receptor (GR) expression in the MG epithelium. Surprisingly, given that chemical carcinogens increase MG cancer risk by preventing normal terminal end bud (TEB) differentiation, chronic isolation stress did not alter TEBs. Instead, isolation blunted MG growth and alveolobular differentiation and reduced epithelial cell proliferation in these structures. Social isolation also enhanced corpora luteal progesterone at all ages but reduced estrogenization only in early adulthood, a pattern that precludes modulated ovarian function as a sufficient mechanism for the effects of isolation on MG development. This longitudinal study of natural variation provides an integrated view of MG development and the importance of increased GR activation in nulliparous ductal growth and alveolobular differentiation. Thus, social isolation and its physiological sequelae disrupt MG growth and differentiation and suggest a contribution of stress exposure during puberty and young adulthood to the previously observed increase in invasive MG cancer observed in chronically socially-isolated adult Sprague-Dawley rats.

KW - Alveolobular development

KW - Mammary gland

KW - Puberty

KW - Stress

KW - Terminal end buds

KW - Young adulthood

UR - http://www.scopus.com/inward/record.url?scp=85045856017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045856017&partnerID=8YFLogxK

U2 - 10.1007/s10911-018-9392-4

DO - 10.1007/s10911-018-9392-4

M3 - Article

C2 - 29687293

AN - SCOPUS:85045856017

VL - 23

SP - 59

EP - 73

JO - Journal of Mammary Gland Biology and Neoplasia

JF - Journal of Mammary Gland Biology and Neoplasia

SN - 1083-3021

IS - 1-2

ER -