Subject(s)
Intracranial Aneurysm/etiology , Lupus Erythematosus, Systemic/complications , Stroke/complications , Vasculitis, Central Nervous System/complications , Angiography, Digital Subtraction , Carotid Arteries/diagnostic imaging , Female , Humans , Lupus Erythematosus, Systemic/diagnosis , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Vasculitis, Central Nervous System/diagnosis , Young AdultSubject(s)
Female , Humans , Middle Aged , Deglutition Disorders , Hyperostosis, Diffuse Idiopathic Skeletal , Syndrome , SpineABSTRACT
BACKGROUND: Parathyroid hormone-related protein (PTHrP) is the primary factor responsible for humoral hypercalcemia of malignancy. The hypercalcemic actions of PTHrP occur via stimulation of renal distal tubular calcium reabsorption and increased osteoclastic bone resorption. These effects of PTHrP are thought to be mediated through a common parathyroid hormone (PTH)/PTHrP receptor. In addition to the well-established role of PTHrP in bone remodeling, PTHrP is believed to be an important mediator of cellular growth and differentiation in a number of nonbony tissues. We recently demonstrated abundant expression of PTHrP in normal and malignant human prostatic tissues, and in cultured prostatic epithelial cells. METHODS: In vitro assays were used to test growth-regulatory activity of synthetic and endogenous PTHrP peptides on normal prostatic epithelial cells. RESULTS: No growth-regulatory activity could be demonstrated. CONCLUSIONS: PTHrP is not an autocrine growth factor for normal prostatic epithelial cells.
Subject(s)
Parathyroid Hormone/pharmacology , Prostate/drug effects , Proteins/pharmacology , Cell Count/drug effects , Cell Division/drug effects , Culture Media, Serum-Free/chemistry , Humans , Male , Parathyroid Hormone/antagonists & inhibitors , Parathyroid Hormone-Related Protein , Prostate/cytology , Proteins/antagonists & inhibitorsABSTRACT
Parathyroid hormone-related protein (PTHrP) has previously been shown to be expressed in human prostatic tissue and in prostatic cancer cell lines. In the present study, PTHrP immunoreactivity was detected in the glandular epithelium of normal prostate and benign prostatic hyperplasia (BPH), as well as in prostatic adenocarcinoma (CaP). Epithelial cell cultures derived from normal, BPH, and CaP tissues were also stained by antibodies against PTHrP, and northern analysis revealed multiple transcripts of PTHrP in the cellular RNA. PTHrP (1-34) was measurable by radioimmunoassay (RIA) in media conditioned by the prostatic epithelial cell cultures, and PTHrP accumulated in conditioned media during a 72 hr time course. Addition of complete growth medium to starved cells resulted in increased PTHrP mRNA levels by 1 hr, with maximal stimulation at 8-24 hr. Several individual factors contained in the complete growth medium were tested for their ability to regulate PTHrP expression. Epidermal growth factor (EGF) was the major inducer of PTHrP expression, while cholera toxin, bovine pituitary extract, hydrocortisone, and insulin had minimal or no effect on PTHrP transcript levels. Since each of these factors is growth stimulatory, the unique ability of EGF to induce PTHrP is apparently unrelated to mitogenicity. 1,25-Dihydroxyvitamin D3[1,25(OH)2D3], an inhibitor of PTHrP expression in several other cell types, had no effect on steady-state levels of PTHrP mRNA expressed by epithelial cells in complete growth medium, although prostate cells have vitamin D receptors and are responsive to 1,25(OH)2D3 in other ways. Our results indicate that PTHrP expression is not confined to the neuroendocrine cells of the human prostate and that our culture system can be used as a model to investigate the role of PTHrP in the prostate.
