Administration of Additional Phosphorylated Prolactin During Pregnancy Inhibits Mammary Ductal Branching and Promotes Premature Lobuloalveolus Development

Abstract

Prolactin (PRL) is a hormone recognized as having both proliferative and differentiative activities in the mammary gland. Current theory proposes that it is the coexisting steroidal environment which dictates whether PRL is proliferative or differentiative. Preliminary data, presented as part of the initial proposal, however, suggested that it was the form of PRL released that dictated whether proliferation or differentiation would occur. By form of PRL we mean whether the PRL is released from the pituitary as an unmodified polypeptide or whether it is phosphorylated. To study this issue, we have produced recombinant, unmodified PRL (U-PRL) and a recombinant, molecular mimic of phosphorylated PRL, S179D PRL. In the studies conducted during the first year, we have confirmed our initial observations that U-PRL promotes growth, while S179D PRL inhibits growth and promotes differentiation. These effects were shown to be independent of progesterone, estrogen, corticosterone and placental lactogens and hence are likely to be direct effects of the different PRL forms on the mammary gland. In vitro studies have shown that treatment with S179D PRL markedly increases the ratio of short to long receptors, suggesting a mechanism which could mediate a switch from a proliferative to a differentiative response.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2001
Accession Number
ADA396550

Entities

People

  • Ameae M. Walker

Organizations

  • University of California, Riverside

Tags

DTIC Thesaurus Topics

  • Anti-Bacterial Agents
  • Biomedical Research
  • Blood
  • Breast Cancer
  • Carcinoma
  • Cells
  • Electronic Mail
  • Gene Expression
  • Glands
  • Growth Factors
  • Hormones
  • Mammary Glands
  • Observation
  • Pregnancy
  • Progesterone
  • Proteins
  • Three Dimensional

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology (Cancer Research).