Mechanisms of inhibition of human benign prostatic hyperplasia in vitro by the luteinizing hormone-releasing hormone antagonist cetrorelix
Agnieszka Siejka
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education,
Divisions of Hematology/Oncology and Endocrinology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorCorresponding Author
Andrew V. Schally
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education,
Department of Pathology, and
Divisions of Hematology/Oncology and Endocrinology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA
Andrew V. Schally or Nektarios Barabutis, Research Service (151), Veterans Affairs Medical Center, 1201 North-west 16th Street, Miami, FL 33125, USA.e-mail: [email protected]@gmail.comSearch for more papers by this authorNorman L. Block
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education,
Department of Pathology, and
Divisions of Hematology/Oncology and Endocrinology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorCorresponding Author
Nektarios Barabutis
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education,
Department of Pathology, and
Andrew V. Schally or Nektarios Barabutis, Research Service (151), Veterans Affairs Medical Center, 1201 North-west 16th Street, Miami, FL 33125, USA.e-mail: [email protected]@gmail.comSearch for more papers by this authorAgnieszka Siejka
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education,
Divisions of Hematology/Oncology and Endocrinology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorCorresponding Author
Andrew V. Schally
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education,
Department of Pathology, and
Divisions of Hematology/Oncology and Endocrinology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA
Andrew V. Schally or Nektarios Barabutis, Research Service (151), Veterans Affairs Medical Center, 1201 North-west 16th Street, Miami, FL 33125, USA.e-mail: [email protected]@gmail.comSearch for more papers by this authorNorman L. Block
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education,
Department of Pathology, and
Divisions of Hematology/Oncology and Endocrinology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorCorresponding Author
Nektarios Barabutis
Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education,
Department of Pathology, and
Andrew V. Schally or Nektarios Barabutis, Research Service (151), Veterans Affairs Medical Center, 1201 North-west 16th Street, Miami, FL 33125, USA.e-mail: [email protected]@gmail.comSearch for more papers by this authorAbstract
OBJECTIVE
To assess the mechanism by which the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix exerts its effects in men with benign prostatic hyperplasia (BPH), as it produces a long-lasting improvement in lower urinary tract symptoms that is only partly accounted for by the transient reduction in testosterone levels, and the beneficial results could be due to direct inhibitory effects of cetrorelix on the prostate exerted through prostatic LHRH receptors.
MATERIALS AND METHODS
Using the BPH-1 cell line we evaluated the effects of cetrorelix in vitro on the proliferation and the expression of receptors for LHRH, epidermal growth factor (EGF), α1A-adrenergic receptor, STAT-3 transcription factor and the response to growth factors insulin-like growth factor (IGF)-1 and -II and fibroblast growth factor (FGF)-2.
RESULTS
There was expression of LHRH receptors in the human BPH-1 cell line. Cetrorelix had inhibitory effects on the proliferation rate of BPH-1 cells, also reflected by the decrease in the expression of the proliferating cell nuclear antigen (PCNA). Cetrorelix inhibited the stimulatory effect of the growth factors IGF-I and -II and FGF-2 on the proliferation of this line. Cetrorelix also downregulated the expression of the receptors for LHRH and EGF, as well as of α1A-adrenergic receptors, and inhibited the activation of the STAT3 transcription factor.
CONCLUSIONS
The results show that in vitro cetrorelix can directly inhibit the proliferation rate of the human BPH-1 cell line by counteracting growth factors like IGF-I and -II and FGF-2, and downregulating the LHRH receptor and α-adrenergic receptors, as well as transcription factors.
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