Abstract
The interaction of progesterone (PG), 17-hydroxyprogesterone (17-OHPG), 21-hydroxyprogesterone (21-OHPG), medroxyprogesterone (MP), medroxyprogesterone acetate (MPA), and dydrogesterone (DYG), with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) multilamellar liposome, was investigated as a function of drug concentration using Fourier transform infrared spectroscopy and differential scanning calorimetry. The results reveal that progesterone and its derivatives changed the physical properties of the DPPC bilayers by decreasing the main phase-transition temperature (T m) and enthalpy (ΔH m), abolishing the pre-transition and disordering the membrane. From the thermodynamic parameters analysis, we concluded that PG, 21-OHPG, and MPA are localized inside the membrane. Whereas, the insertion of 17-OHPG in the lipid bilayers cannot be excluded in view of the significant decrease in the transition enthalpy at two molar ratios. MP and DYG are rather localized near the polar heads of phospholipids at the interface water-lipid bilayer. PG derivatives increase the membrane fluidity in the order: PG ≈ 21-OHPG ≈ MPA > 17-OHPG > MP ≈ DYG. The distinct effects produced by steroids are discussed in terms of hydrophobicity and chemical structure.
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References
Al-Asmakh M (2007) Reproductive functions of progesterone. Middle East Fertil Soc J 12(3):147–152
Alvarez Nunez FA, Yalkowsky SH (1997) Correlation between log P and ClogP for some steroids. J Pharm Sci 86(10):1187–1189
Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13:238–252
Bhardwaj U, Burgess DJ (2010) Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone. Int J Pharm 388:181–189
Biruss B, Dietl R, Valenta C (2007) The influence of selected steroid hormones on the physicochemical behavior of DPPC liposomes. Chem Phys Lipids 148:84–90
Boyar H, Severcan F (1997) Oestrogen-phospholipid membrane interactions: an FTIR study. J Mol Struct 408(409):269–272
Carlson JC, Gruber MY, Thompson JE (1983) A Study of the interaction between progesterone and membrane lipids. Endocrinology 113:190
Colombo D, Ferraboschi P, Prestileo P, Toma L (2006) A comparative molecular modeling study of dydrogesterone with other progestational agents through theoretical calculations and nuclear magnetic resonance spectroscopy. J Steroid Biochem Mol Biol 98:56–62
Cong W, Liu Q, Liang Q, Wang Y, Luo G (2009) Investigation of the interactions between pirarubicin and phospholipids. Biophys Chem 143:154–160
De Ziegler DF (2000) Progesterone and progestins: applications in gynecology. Steroids 65:671–679
Dicko A, Morissette M, Ben Ameur S, Pézolet M, Di Paolo T (1999) Effect of estradiol and tamoxifen on brain membranes: investigation by infrared and fluorescence spectroscopy. Brain Res Bull 49:401–405
Dunn JF, Nisula BC, Rodbard D (1981) Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab 53:58–68
Ehring GR, Kerschbaum HH, Eder C, Neben AL, Fanger CM, Khoury RM et al (1998) A nongenomic mechanism of progesterone-mediated immunosuppression: inhibition of K+ channels, Ca2+ signaling, and gene expression in T lymphocytes. J Exp Med 188(9):1593–1602
El Maghraby GM, Williams AC, Barry BW (2005) Drug interaction and location in liposomes: correlation with polar surface areas. Int J Pharm 292:179–185
Elhissi AM, O’Neill MA, Roberts SA, Taylor KM (2006) A calorimetric study of dimyristoylphosphatidylcholine phase transitions and steroid–liposome interactions for liposomes prepared by thin film and proliposome methods. Int J Pharm 320:124–130
Gallay J, De Kruijff B (1984) Corticosteroids as effectors of lipid polymorphism of dielaidoylglycerophosphoethanolamine. Eur J Biochem 142:105–112
Habib L, Khreich N, Jraij A, Abbas S, Magdalou J, Charcosset C et al (2013) Preparation and characterization of liposomes incorporating cucurbitacin E, a natural cytotoxic triterpene. Int J Pharm 13:238–252
Heimburg T (2000) A model for the lipid pretransition: coupling of ripple formation with the chain-melting transition. Biophys J 78:1154–1165
Iswari S, Colas AE, Karavolas HJ (1986) Binding of 5 alpha dihydroprogesterone and other progestin to female rat anterior pituitary nuclear extracts. Steroids 47(2–3):189–203
Jain MK, Wu NM (1977) Effect of small molecules on the dipalmitoyl lecithin liposomal bilayer: phase transition in lipid bilayer. J Membr Biol 34:157–201
Kazanci N, Toyran N, Haris P, Severcan F (2001) Vitamin D2 at high and low concentrations exert opposing effects on molecular order and dynamics of dipalmitoyl phosphatidylcholine membranes. Spectroscopy 15:47–55
Korkmaz F, Severcan F (2005) Effect of progesterone on DPPC membrane: evidence for lateral phase separation and inverse action in lipid dynamics. Arch Biochem Biophys 440:141–147
Korkmaz F, Kırbıyık H, Severcan F (2005) Concentration dependent different action of progesterone on the order, dynamics and hydration states of the head group of dipalmitoyl-phosphatidylcholine membrane. Spectroscopy 19:213–219
Lewis R, McElhaney R (1998) The structure and organization of phospholipid bilayers as revealed by infrared spectroscopy. Chem Phys Lipids 96:9–21
Liang Y, Belford S, Tang F, Prokai L, Simpkins J, Hughes J (2001) Membrane fluidity effects of estratrienes. Brain Res Bull 54:661–668
McEwen BS (1994) Steroid hormone actions on the brain: when is the genome involved? Horm Behav 28(4):396–405
Mendoza C, Soler A, Tesarik J (1996) Nongenomic steroid action: independent targeting of a plasma membrane calcium channel and a tyrosine kinase. Biochem Biophys Res Commun 210(2):518–523
Olive DL (2002) Role of progesterone antagonists and new selective progesterone receptor modulators in reproductive health. Obstet Gynecol Surv 57:55–63
Prades J, Vogler O, Alemany R, Gomez-Florit M, Funari S, Ruiz-Gutierrez V et al (2011) Plant pentacyclic triterpenic acids as modulators of lipid membrane physical properties. Biochim Biophys Acta 1808:752–760
Sanchez-Bueno AW (1991) Studies of conformation and interaction of the cyclohexenone and acetyl group of progesterone with liposomes. J Steroid Biochem Mol Biol 38:171–179
Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW et al (2003) Classification and pharmacology of progestins. Maturitas 46:7–16
Skiba ML, Barbot C, Bounoure F, Joudieh S, Skiba M (2006) Solubility and dissolution rate of progesterone-cyclodextrin-polymer systems. Drug Dev Ind Pharm 32:1043–1058
Soderpalm AH, Lindsey S, Purdy RH, Hauger R, Wit H (2004) Administration of progesterone produces mild sedative-like effects in men and women. Psychoneuroendocrinology 29:339–354
Sun Y, Cai J, Ma F, Lu P, Huang H, Zhou J (2012) miR-155 mediates suppressive effect of progesterone on TLR3, TLR4-triggered immune response. Immunol Lett 146:25–30
Torres-Cartas S, Villanucva-Carmanãs R, Garcia-Alvarez-Coque M (2000) Retention-structure relationship studies for some steroidal hormones in micellar liquid chromatography. Chromatographia 51(9–10):577–585
Tsuda K, Kinoshita Y, Nishio I (2002) Synergistic role of progesterone and nitric oxide in the regulation of membrane fluidity of erythrocytes in humans: an electron paramagnetic resonance investigation. Am J Hypertens 15(8):702–708
Vijayan R, Biggin PC (2008) A steroid in a lipid bilayer: localization, orientation, and energetics. Biophys J 95:45–47
Wenz JJ (2012) Predicting the effect of steroids on membrane biophysical properties based on the molecular structure. Biochim Biophys Acta 1818:896–906
Whiting KP, Restall CJ, Brain PF (2000) Steroid hormone-induced effects on membrane fluidity and their potential roles in non-genomic mechanisms. Life Sci 67:743–757
Wood EJ (2006) Marks’ basic medical biochemistry: a clinical approach (second edition). Biochem Mol Biol Educ 34:395
Zhang Y, Wang Z, Ma Z, Cheng Y (2008) Characterization of progesterone derivatives by LC-DAD-ESI/MSn and its application to the identification of impurities in flurogestone acetate. Chromatographia 68:903–909
Zhao X, Liu L, Liu D, Fan H, Wang Y, Hu Y et al (2012) Progesterone enhances immunoregulatory activity of human mesenchymal stem cells via PGE2 and IL-6. Am J Reprod Immunol 68:290–300
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Authors thank the Doctoral School of Sciences and Technologies at the Lebanese University for supporting the Bioactive Molecules Research Group.
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Abboud, R., Greige-Gerges, H. & Charcosset, C. Effect of Progesterone, Its Hydroxylated and Methylated Derivatives, and Dydrogesterone on Lipid Bilayer Membranes. J Membrane Biol 248, 811–824 (2015). https://doi.org/10.1007/s00232-015-9803-z
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DOI: https://doi.org/10.1007/s00232-015-9803-z