Endocrine
The authors have previously shown that the type 1 insulin-like growth factor receptor (IGF-1R) is decreased in the transformation from benign to malignant human prostate epithelial cells in vivo. Further, in a well-described human SV40-T immortalized human epithelial cell system beginning with the immortalized, but rarely tumorigenic P69SV40-T cell line, to the highly tumorigenic and metastatic M12...
Human marrow was obtained as material discarded during total hip replacement and was established in culture with phenol red-free α-MEM with 10% fetal bovine serum (FBS) and antibiotics. Insulin-like growth factor I (IGF-I) and its binding proteins were secreted by human marrow cells, in amounts that increased with time in culture. Western ligand blotting showed that insulin-like growth factor binding...
The loss or functional inactivation of tumor suppressor genes appears to be one of the most fundamental genetic mechanisms of tumorigenesis, and rational insights into the signaling pathways of tumor suppressor genes have emerged as a successful strategy of identifying novel drug discovery targets downstream of the tumor suppressor protein itself. Elucidation of novel pathways downstream of p53 have...
Over the last several years, the authors have studied the relationship of insulin-like growth factors (IGFs) and the insulin-like growth factor binding proteins (IGFBPs) in the circulation in a number of clinical settings. Patterns have emerged that seem to be characteristic of various conditions. In aging, there are marked decreases in IGF-I, and-II, normal levels of IGFBP-3, and marked increases...
Because impaired bone formation is a major contributor to the pathogenesis of senile (type II) osteoporosis, and because insulin-like growth factors (IGFs) have been shown to be important stimulators of bone formation in vitro and in vivo, studies have been focused towards clarifying the role of IGF system in the age-related impairment in bone formation. To evaluate if changes in circulating and bone...
Insulin-like growth factor binding protein (IGFBP) degrading proteinase activities have been described in biological fluids and conditioned media from numerous cell lines. To identify and characterize IGFBP-degrading proteinases, our laboratory has developed IGFBP substrate zymography. Herein, we illustrate how IGFBP substrate zymography can be used both to identify candidate IGFBP-degrading proteinases...
The insulin-like growth factor binding proteins (IGFBPs) are a family of seven structurally homologous proteins that bind insulin-like growth factor 1 (IGF-1) and IGF-II with high affinity, thereby modulating the actions of IGFs. Several lines of recent evidence from various cell systems have suggested that IGFBPs, especially IGFBP-3, may play more active, IGF-independent, roles in growth regulation...
Loss of muscle mass and strength are well-known consequences of aging. The growth hormone/IGF-I pathway is both impaired with aging and essential for growth and maintenance of skeletal muscle. Despite this, growth hormone (GH) replacement has not been effective in increasing muscle mass and strength in the elderly. Possible explanations for this failure include 1. The presence of other age-related...
Remarkable decreases in growth hormone (GH) secretion accompany healthy aging. The pathophysiology of this hyposomatotropism is confounded by concurrent changes in body composition (with increased visceral fat), physiological declines in estrogen and androgen concentrations, differences in gender responses to aging, and alterations not only in the quantity of GH secreted, but also (as more recently...
Human chorionic gonadotropin (hCG), purified from the urine of 14 individuals with normal pregnancy, diabetic pregnancy, hydatidiform mole, or choriocarcinoma, plus two hCG standard preparations, was examined for concurrent peptide-sequence and asparagine (N)- and serine (O)-linked carbohydrate heterogeneity. Protein-sequence analysis was used to measure amino-terminal heterogeneity and the “nicking”...
Proforms of gastrointestinal peptide hormones and neuropeptides are processed, in part, by prohormone convertases (PCs) to mature, biologically active peptides. The purpose of this study was to characterize the mRNA levels of PC-6 isoforms, PC-6A and PC-6B, in the gastrointestinal tract and pancreas of the rat, and to investigate the effects of a fasting and refeeding regimen, and a high-fat diet...
Several Gi-protein-coupled receptors normally expressed in islet β-cells inhibit insulin secretion on binding of their respective agonists. To study the effect of supraphysiologic expression of such a receptor in insulin-secreting β-cells, we stably transfected cDNA encoding the mouse α2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected, each overexpressing the α...
Although it is generally accepted that tubulin plays an important role in G-protein-mediated signal transduction in a variety of systems, the mechanism of this phenomenon is not completely understood. G-protein-tubulin interaction at the cell membrane and the cytosol, and the influence of such an interaction on cellular signaling are discussed in this review article. Because the diameter of...
Both 17β-estradiol (17β) and the vitamin D metabolites, 1,25-(OH)2D3 (1,25) and 24,25-(OH)2D3 (24,25), regulate endochondral bone formation in vivo and in vitro. The effects of 17β are sex-specific and cell maturation-dependent. Similarly, the effects of 1,25 and 24,25 are cell maturation-dependent, with 1,25 affecting growth zone chondrocytes (GC) and 24,25 affecting resting zone chondrocytes (RC)...
We evaluated the influence of continual estrogen replacement therapy (ERT) as presently practiced by postmenopausal women with conjugated estrogens and medroxyprogesterone acetate (MPA) on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and cellular immunity. Thirty-nine postmenopausal women were evaluated (12 on no replacement, 14 on estrogen only, and 13 on estrogen and MPA). In...
Pituitary adenylate cyclase activating polypeptide (PACAP) is a new member of the secretin/VIP family of peptides. The specific receptor for PACAP has been cloned in rat, human, and bovine tissues. The distribution of the transcripts of PACAP receptor genes has been studied in various tissues usingin situ hybridization. However, the unavailability of a specific antibody against the PACAP receptor...