Local insulin-like growth factor-II mediates prolactin-induced mammary gland development

Russell C. Hovey, Jessica Harris, Darryl L. Hadsell, Adrian V. Lee, Christopher J. Ormandy, Barbara K. Vonderhaar

Research output: Contribution to journalArticle

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Abstract

Prolactin (PRL) is a major determinant of mammary epithelial cell proliferation during alveolar development in sexually mature and pregnant mice. To date, it has not been clear whether PRL effects these responses alone or by also invoking the action of autocrine/paracrine growth factors. In this study, we provide evidence that part of the effect of PRL on mammary gland growth is mediated by IGF-II. During sexual maturity and in early pregnancy, the level of IGF-II mRNA in the mammary gland was increased concurrent with increased PRL receptor expression. The level of IGF-II mRNA was reduced in mammary tissue from PRL receptor-/- mice during early pregnancy, and explants of mouse mammary gland and HC11 mammary epithelial cells both increased their expression of IGF-II after exposure to PRL in vitro. These findings coincided with the demonstration that IGF-II stimulated alveolar development in mammary glands in whole organ culture. PRL was most efficacious in stimulating IGF-II gene transcription from promoter 3 of the mouse IGF-II gene in vitro. Insight into the mechanism by which PRL induced IGF-II expression was provided by the fact that it was blocked by the Jak2 inhibitor AG490 and the MAPK inhibitor PD98059. Finally, induction of insulin receptor substrate (IRS)-1 in the mammary glands of PRL-treated mice and induction of IRS-1 and IRS-2 after treatment with PRL plus progesterone indicates that these molecules are induced by PRL as potential signaling intermediates downstream from IGF-I/insulin receptors. Together, these data demonstrate a role for IGF-II as a mediator of PRL action in the mouse mammary gland during ductal branching and alveolar development.

Original languageEnglish (US)
Pages (from-to)460-471
Number of pages12
JournalMolecular Endocrinology
Volume17
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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Insulin-Like Growth Factor II
Human Mammary Glands
Prolactin
Insulin Receptor Substrate Proteins
Prolactin Receptors
Breast
Epithelial Cells
Pregnancy
IGF Type 1 Receptor
Messenger RNA
Organ Culture Techniques
Insulin Receptor
Genes
Progesterone
Intercellular Signaling Peptides and Proteins
Cell Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Hovey, R. C., Harris, J., Hadsell, D. L., Lee, A. V., Ormandy, C. J., & Vonderhaar, B. K. (2003). Local insulin-like growth factor-II mediates prolactin-induced mammary gland development. Molecular Endocrinology, 17(3), 460-471. https://doi.org/10.1210/me.2002-0214

Local insulin-like growth factor-II mediates prolactin-induced mammary gland development. / Hovey, Russell C.; Harris, Jessica; Hadsell, Darryl L.; Lee, Adrian V.; Ormandy, Christopher J.; Vonderhaar, Barbara K.

In: Molecular Endocrinology, Vol. 17, No. 3, 01.03.2003, p. 460-471.

Research output: Contribution to journalArticle

Hovey, RC, Harris, J, Hadsell, DL, Lee, AV, Ormandy, CJ & Vonderhaar, BK 2003, 'Local insulin-like growth factor-II mediates prolactin-induced mammary gland development', Molecular Endocrinology, vol. 17, no. 3, pp. 460-471. https://doi.org/10.1210/me.2002-0214
Hovey, Russell C. ; Harris, Jessica ; Hadsell, Darryl L. ; Lee, Adrian V. ; Ormandy, Christopher J. ; Vonderhaar, Barbara K. / Local insulin-like growth factor-II mediates prolactin-induced mammary gland development. In: Molecular Endocrinology. 2003 ; Vol. 17, No. 3. pp. 460-471.
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