Modulation of epididymal delta 4-steroid 5 alpha-reductase activity in vitro by the phospholipid environment.
Cooke GM, Robaire B.
Abstract
Epididymal 5 alpha-reductase converts testosterone to 5 alpha-dihydrotestosterone. The enzyme is localized to the nuclear and microsomal membranes, and using two approaches, we investigated the relationship between 5 alpha-reductase activity and the membrane environment. In the first, nuclear and microsomal membrane fractions were treated with phospholipases to modify specifically the structure of the phospholipid component of the membranes, and the effects of these treatments on the kinetic parameters of 5 alpha-reductase were examined. The second approach was to observe the effects of phospholipids of known structure on solubilized 5 alpha-reductase activity. Treatment of the membrane fractions with phospholipase C increased the Km(app) of both the nuclear and microsomal 5 alpha-reductases for testosterone. Phospholipase A2 treatment also increased the Km(app) of the microsomal enzyme, but in contrast, the Km(app) of the nuclear 5 alpha-reductase for testosterone was unaffected. This demonstrated a fundamental difference in the role of the membrane environment in the expression of 5 alpha-reductase activity in these subcellular compartments. The ability of phospholipids to enhance the activity of solubilized 5 alpha-reductase was highly specific and structure related. Only phosphatidylcholines containing either unsaturated acyl chains or saturated acyl chains of 12 carbon atoms were found to activate 5 alpha-reductase. The most potent activator was dilauroyl phosphatidylcholine, which reduced the Km(app) values of both nuclear and microsomal 5 alpha-reductases for testosterone, without affecting the concentration of active 5 alpha-reductase (Vmax(app) ). This is the first time that an activator of 5 alpha-reductase has been found. These findings suggest that epididymal 5 alpha-reductase activity may be regulated by changes in the phospholipid environment.
ncbi.nlm.nih.gov/pubmed/3997884
Effect of dilauroylphosphatidylcholine liposomes on motility, induction of the acrosome reaction, and subsequent egg penetration of ram epididymal sperm.
- J K Graham,
- J P Nolan and
- R H Hammerstedt
- Biochemistry Program, Pennsylvania State University, University Park 16802.
Abstract
The effects of dilauroylphosphatidylcholine (PC12) on ram epididymal sperm motility, acrosome reaction (AR) induction, plasma membrane permeability, mitochondrial function, and sperm penetration into zona-free hamster eggs were determined. PC12 (50 microM) induced cell motility in caput and cauda sperm, as measured by subjective estimation and automated motility analysis. Motion parameters of treated caput sperm approached those of control ejaculated sperm. Flow cytometric analysis revealed that membrane permeability to propidium iodide and mitochondrial uptake of rhodamine 123 changed during epididymal transit. PC12 induced the AR in sperm from all epididymal regions relative to control incubated sperm (caput 17% vs. control 8%; corpus 29% vs. control 13%; proximal cauda 48% vs. control 4%; distal cauda 51% vs. control 9%). After PC12 treatment, egg penetration by sperm was increased for sperm from the corpus (corpus 7% vs. control 0%) and cauda (proximal 48% vs. control 0%; distal 51% vs. control 0%), but not for caput sperm (caput 0% vs. control 0%). These studies establish that some sperm in each region of the epididymis possess the capacity for movement and the AR. Caput sperm, however, were unique in that they could not penetrate eggs. Additional maturational changes must occur in the caput and/or corpus epididymidis before penetration capacity can be expressed.
biolreprod.org/content/44/6/1092
Effect of Dilauroylphosphatidylcholine on Human Spermatozoa:
andrologyjournal.org/cgi/reprint/13/3/260.pdf
A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects
Jae Man Lee
Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis1, 2. Structural studies have identified phospholipids as potential LRH-1 ligands3, 4, 5, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis
Nature 25 May 2011
sciencechatforum.com/viewtopic.php?f=18&t=18923
Binding of nystatin and amphotericin B with sterol-free L-dilauroylphosphatidylcholine bilayers resulting in the formation of dichroic lipid superstructures.
Milhaud J, Michels B.
Source
Laboratoire de Physicochimie Biomoleculaire et cellulaire (ESA 7033), Université Paris VI, France.
Abstract
Interactions of multilamellar vesicles (MLV) of dilauroylphosphatidylcholine (DLPC) with the polyene antibiotics, amphotericin B (AmB) and nystatin (Ny), were followed by circular dichroism (CD). These interactions proceed with both antibiotics through a slow association with high [DLPC]/[antibiotic] stoichiometric molar ratios (> or = 130), at room temperature for which DLPC membranes are in a fluid state. Microscopic investigations of the spatial distributions of the antibiotic and the MLV in the mixtures revealed that MLV form clusters inside which the antibiotic is strongly concentrated and lipid superstructures appear. Concomitantly with the appearance of these superstructures a DLPC dichroic signal emerges. This observation indicates that the chiral properties of antibiotic oligomers can induce a chirality of the DLPC molecules which are bound to them. These results support the hypothesis of a recent molecular modeling of AmB oligomers which postulates that their chiral properties result from a chiral assemblage of antibiotic molecules (Millié et al., J. Phys. Chem. B, in press).
PMID:
10533264
[PubMed - indexed for MEDLINE]
ncbi.nlm.nih.gov/pubmed/10533264
May be thats why it might help!