PRL is a 23 kDa hormone that is expressed at pituitary and extrapituitary sites. Although the breast expresses PRL, it is not known what compartments as well as cell types within the breast are responsible for PRL production, how much PRL is released from these tissues and how PRL expression is regulated. Breast PRL can contribute to breast development, local adipose tissue metabolism as well as to breast cancer progression. By identifying the sources of breast PRL and how it is regulated, the function of PRL as an autocrine/paracrine factor can be determined.
Our hypotheses were that PRL is produced by the major compartments of the breast and is regulated differently than pituitary PRL. Using human adipose and glandular explants and primary breast preadipocytes in vitro, the specific aims were to: 1) determine if biologically active PRL is produced by breast explants, 2) ascertain if PRL is regulated by ovarian steroids in these tissues, 3) verify whether breast PRL is transcribed from the superdistal promoter, 4) identify the adipose cell types responsible for PRL production, 5) identify putative ligand that may stimulate/inhibit PRL expression and release from adipocytes, and 6) compare major regions within the superdistal promoter that regulates PRL expression in primary preadipocytes, liposarcoma-derived adipocytes and breast cancer cells.
We found that PRL expression increases in a time-dependent manner in both adipose and glandular explants in vitro. PRL release also increases over time in culture and is 10-12 fold higher in adipose than glandular tissue. PRL release is decreased in glandular, but not adipose, tissue by progesterone, while estradiol has no effect on either tissue. Within adipose tissue, PRL is expressed at low levels in both primary preadipocytes and freshly isolated mature adipocytes. During differentiation PRL expression increases transiently during the commitment phase of adipogenesis. PRL expression/release in preadipocytes is stimulated by the cAMP activators IBMX, isoproterenol and PACAP. PRL transcription is driven by the superdistal promoter in primary preadipocytes, SW872, LS14 liposarcoma cells and Jurkat lymphoblast cells, but with notable differences in the relative activity of the various regions of the promoter.
|School:||University of Cincinnati|
|Department:||Cell and Molecular Biology|
|School Location:||United States -- Ohio|
|Source:||DAI-B 79/10(E), Dissertation Abstracts International|
|Keywords:||Adipogenesis, Adipose, Breast, Prolactin|
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