ABSTRACT
Activin, a member of the transforming growth factor-beta superfamily of growth and differentiation factors, has a number of actions in embryonic as well as adult tissues. These actions are mediated via a family of receptors containing two subtypes and at least two members of each subtype. Recent evidence demonstrates that activin-responsive cell lines containing different subsets of these receptors are valuable models for dissecting functional relationships among receptor subtype, signal transduced, and response obtained. TT cells, derived from a p53(-/-)/alpha-inhibin(-/-) mouse testicular tumor, respond to activin by proliferating, a response that can be inhibited by follistatin (FS) treatment. Using semiquantitative RT-PCR methods, we characterized steady state messenger RNA (mRNA) levels for the inhibin/activin subunits, FS, and activin receptor subtypes under basal conditions and in the presence of activin or FS. These cells produced ample immunoreactive activin A and FS, necessitating higher treatment doses to observe any modulation of cellular proliferation. Furthermore, in the presence of exogenous activin, mRNA levels for activin receptor type IIA (ACTRIIA) and betaA were significantly and profoundly suppressed. In addition, both ACTR1B and ACTRIIB were detectable and down-regulated by exogenous activin, although not to the degree observed for ACTRIIA and betaA. Finally, activin treatment at the higher doses, which decreased activin receptor mRNA levels, resulted in inhibition of cellular proliferation. Taken together with previous observations, our results support the model that these tumor cells respond to an autocrine activin signal by proliferating, whereas exogenous or excess activin results in down-regulation of activin receptor and activin biosynthesis, suggesting a potential autocrine/paracrine mechanism by which activin can modulate its own signal.
Subject(s)
Inhibins/physiology , RNA, Messenger/analysis , Receptors, Growth Factor/genetics , Testicular Neoplasms/metabolism , Activin Receptors , Activins , Animals , Cell Division , Follistatin , Glycoproteins/genetics , Glycoproteins/metabolism , Male , Mice , Testicular Neoplasms/pathology , Tumor Cells, CulturedABSTRACT
The effects of consuming foods containing 0 (control), 3.4, 6.8, or 10.2 g psyllium seed husk (PSH)/d for 24 wk on the serum lipid profile were assessed in this randomized, double-blind controlled study. Men and women (n = 286) with LDL-cholesterol concentrations between 3.36 and 5.68 mmol/L (130 and 220 mg/dL) were randomly assigned to one of four treatment groups after following a low-fat diet for > or = 8 wk. At week 24, LDL cholesterol was 3% above baseline in the control group. In the group consuming 10.2 g PSH/d, LDL cholesterol remained below baseline during treatment, with a value 5.3% below that of the control group at week 24 (P < 0.05 compared with the control group). No significant differences were observed in HDL cholesterol or triacylglycerol. Although modest, the effect of 10.2 g PSH/d on LDL cholesterol (relative to the control) persisted throughout the 24-wk treatment period, indicating potential for long-term benefit.
Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dietary Fiber/therapeutic use , Hypercholesterolemia/diet therapy , Psyllium/therapeutic use , Triglycerides/blood , Adult , Aged , Aged, 80 and over , Diet Records , Dietary Fiber/administration & dosage , Dietary Fiber/adverse effects , Double-Blind Method , Female , Humans , Hypercholesterolemia/blood , Male , Middle Aged , Patient Compliance , Psyllium/administration & dosage , Psyllium/adverse effectsABSTRACT
Marine oil plus simvastatin is an effective therapy for improving serum triglycerides, non-high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with combined hyperlipidemia. Concurrent administration does not attenuate the individual effects of either marine oil or simvastatin on the serum lipid profile.
Subject(s)
Fish Oils/therapeutic use , Hyperlipidemia, Familial Combined/drug therapy , Hypolipidemic Agents/therapeutic use , Lovastatin/analogs & derivatives , Double-Blind Method , Drug Therapy, Combination , Female , Fish Oils/administration & dosage , Humans , Hypolipidemic Agents/administration & dosage , Lovastatin/administration & dosage , Lovastatin/therapeutic use , Male , Simvastatin , Triglycerides/bloodABSTRACT
Follistatin (FS) is the principle high affinity activin-binding protein in tissues such as the pituitary and ovary as well as in serum. In addition, the activin-binding peaks identified after gel filtration of serum or human follicular fluid (hFF) exhibited high affinity and low reversibility binding kinetics, with higher concentrations in hFF than serum. This extremely low reversibility was also observed for recombinant human follistatin 288 (rhFS288) under a variety of incubation conditions, further supporting the identification of the serum and hFF activin-binding proteins as FS. Using enhanced resolution gel filtration, immunoprecipitation with monoclonal antibodies to rhFS288, and sulfated carbohydrate binding, activin-FS complexes in hFF and serum differed. The activin-FS complex in hFF elutes at approximately 200-300 kDa, is immunoprecipitated by anti-hFS288 monoclonal antibodies, and binds to sulfate Cellufine matrix, all characteristics similar to those of recombinant human FS288. In contrast, the activin binding peak in human serum elutes at an apparent Mr of 60-70 kDa, is no precipitated by anti-rhFS288 monoclonal antibodies, and is weakly bound by sulfate Cellufine matrix, characteristics shared by rhFS315 conditioned medium. As the forms of FS that bind sulfate-containing matrices also bind to cell surface proteoglycans, the molecular differences reported here for serum and hFF activin-binding proteins have implications for potential tissue-specific forms of FS that may well have distinct biological functions.
