title: Effect of polymeric nanoparticle poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) on in vitro luteinizing hormone release from anterior pituitary cells of infantile and adult female rats.
abstract: OBJECTIVE
  Polymeric PEG-b-PLA nanoparticles (NPs) were developed for delivery of poorly water-soluble drugs via blood brain barrier into brain parenchyma. We analyzed neuroendocrine disrupting effects of neonatal exposure of female rats to PEG-b-PLA NPs and diethylstilbestrol (DES) on the function of adenohypophyseal gonadotrophs of infantile or adult rats by examining in vitro luteinizing hormone releasing hormone (LHRH)-induced luteinizing hormone (LH) release.
  
  
  METHODS
  Neonatal female Wistar rats were injected intraperitoneally, daily, from postnatal day (PND) 4 to PND7 with PEG-b-PLA NPs (20 mg.kg b.w.(-1)), DES (4 µg.kg b.w.(-1)) or vehicle. At the necropsy day (PND15 in infantile and the first estrus day after PND176 in adult rats), adenohypophyseal cells were isolated by enzymatic digestion, plated in 96-well plates (5×10(4) cells.well(-1)) in serum-supplemented medium and left to recover for 96 h. LHRH (10-7 mol.L(-1)) treatment was performed in serum-free medium for 60 min and LH levels in culture media were determined by radioimmunoassay.
  
  
  RESULTS
  In all experimental groups, in vitro LHRH treatment significantly stimulated LH release from pituitary cells of infantile but not adult female rats. Neonatal DES treatment increased basal LH secretion from cultured pituitary cells of adult but not infantile rats. In both, infantile and adult rats, neonatal treatment with PEG-b-PLA significantly increased basal and LHRH-induced LH release from pituitary cells compared to corresponding controls and DES-treated group.
  
  
  CONCLUSIONS
  Data indicate that neonatal exposure to PEG-b-PLA NPs may alter pituitary LH release, and thereby modify reproductive system development in infantile female rats leading to reproductive dysfunctions in adult age.
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Sona
authors.initials: S
authors.lastname: Scsukova
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Mlynarcikova
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiss
authors.affiliation: Department of Toxicology, Slovak Medical University, Bratislava, Slovakia.
authors.forename: Eva
authors.initials: E
authors.lastname: Rollerova
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004054:Diethylstilbestrol / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D052681:Gonadotrophs / Q000187:drug effects* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D066298:In Vitro Techniques; D007773:Lactates / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011092:Polyethylene Glycols / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004968:Estrogens, Non-Steroidal; D007773:Lactates; C088513:poly(lactic acid-ethylene glycol); D007987:Gonadotropin-Releasing Hormone; D011092:Polyethylene Glycols; D004054:Diethylstilbestrol; D007986:Luteinizing Hormone