Background: In the current study, we have investigated the individual roles of unmodified, wild-type prolactin (WT PRL) and a molecular mimic of phosphorylated prolactin (S179D PRL) in the normal rat prostate.
Methods: In the first animal experiment, recombinant WT PRL and S179D PRL were delivered to adult male rats at a rate of 14 microg/kg per day for 3 weeks. In the second animal experiment, two subcutaneous (200 microg/kg) injections of long-acting forms of the two PRLs were given to adult male rats on day 1 and day 22 for a total of 5.5 weeks of treatment.
Results: The different forms of PRL had opposite effects on the normal rat prostate, independently of androgens. WT PRL promoted morphologic changes in prostate epithelium consistent with preparation for cell proliferation, whereas S179D PRL produced morphologic evidence of a more differentiated epithelium. Northern blot analysis of expression of the two major prostate specific proteins, prostatein and probasin, showed that WT PRL decreased, whereas S179D PRL increased, the expression of the mRNAs for these two proteins. At the same time, S179D PRL reduced both testosterone and dihydrotestosterone levels.
Conclusion: We conclude that PRL is an important modulator of normal rat prostate biology and that different forms of PRL have specific functions. The molecular mimic of phosphorylated PRL, S179D PRL, is the most important in terms of epithelial cell differentiation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/pros.10168 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
S179D Prolactin Sensitizes Human PC3 Prostate Cancer Xenografts to Anti-tumor Effects of Well-Tolerated Doses of Calcitriol.
J Cancer Sci Clin Ther
October 2020
Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA.
Calcitriol has been shown to have multiple anti-prostate cancer effects both and in xenograft models, and associations between low levels of calcitriol and more aggressive forms of prostate cancer have been observed clinically. However, the concentrations of calcitriol required to have a substantive anti-cancer effect are toxic. In previous work, we had observed that the selective prolactin receptor modulator, S179D PRL, sensitized prostate cancer cells to physiological concentrations of calcitriol through an ability to increase expression of the vitamin D receptor.
View Article and Find Full Text PDFProlactin inhibits a major tumor-suppressive function of wild type BRCA1.
Cancer Lett
June 2016
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA. Electronic address:
Even though mutations in the tumor suppressor, BRCA1, markedly increase the risk of breast and ovarian cancer, most breast and ovarian cancers express wild type BRCA1. An important question is therefore how the tumor-suppressive function of normal BRCA1 is overcome during development of most cancers. Because prolactin promotes these and other cancers, we investigated the hypothesis that prolactin interferes with the ability of BRCA1 to inhibit the cell cycle.
View Article and Find Full Text PDFBlockade of estrogen-stimulated proliferation by a constitutively-active prolactin receptor having lower expression in invasive ductal carcinoma.
Cancer Lett
March 2015
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA. Electronic address:
A comprehensive understanding of prolactin's (PRL's) role in breast cancer is complicated by disparate roles for alternatively-spliced PRL receptors (PRLR) and crosstalk between PRL and estrogen signaling. Among PRLRs, the short form 1b (SF1b) inhibits PRL-stimulated cell proliferation. In addition to ligand-dependent PRLRs, constitutively-active varieties, missing the S2 region of the extracellular domain (ΔS2), naturally occur.
View Article and Find Full Text PDFBoth prolactin (PRL) and a molecular mimic of phosphorylated PRL, S179D-PRL, protect the hippocampus of female rats against excitotoxicity.
Neuroscience
January 2014
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autonoma de Mexico, Querétaro 76230, Mexico.
Prolactin (PRL) has many functions in the CNS, including neuroprotection. During lactation, the dorsal hippocampus is protected from excitotoxic kainic acid (KA)-induced cellular damage. We have previously reported that systemic pre-treatment with ovine PRL had similar protective effects in female rats.
View Article and Find Full Text PDFA mimic of phosphorylated prolactin induces apoptosis by activating AP-1 and upregulating p21/waf1 in human prostate cancer PC3 cells.
Oncol Lett
November 2012
Department of Epidemiology and Health Statistics, School of Public Health and Family Medicine;
A mimic of phosphorylated prolactin (S179D PRL) has been demonstrated to inhibit prostate cancer cell growth in vitro and in vivo; however, the mechanisms involved in this process remain unknown. In this study, we identified that a four-day treatment of S179D PRL (1 μg/ml) in human prostate PC3 cancer cells activated JNK, c-fos and c-jun, and led to apoptosis. We also demonstrated that p21/waf1 was upregulated in cells transfected with the human PRL receptor (S1b) following a four-day incubation with S179D PRL (1 μg/ml).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!