title: Identification of Eight Different Isoforms of the Glucocorticoid Receptor in Guinea Pig Placenta: Relationship to Preterm Delivery, Sex and Betamethasone Exposure.
abstract: The placental glucocorticoid receptor (GR) is central to glucocorticoid signalling and for mediating steroid effects on pathways associated with fetal growth and lung maturation but the GR has not been examined in the guinea pig placenta even though this animal is regularly used as a model of preterm birth and excess glucocorticoid exposure. Guinea pig dams received subcutaneous injections of either vehicle or betamethasone at 24 and 12 hours prior to preterm or term caesarean-section delivery. At delivery pup and organ weights were recorded. Placentae were dissected, weighed and analysed using Western blot to examine GR isoform expression in nuclear and cytoplasmic extracts. A comparative examination of the guinea pig GR gene identified it is capable of producing seven of the eight translational GR isoforms which include GRα-A, C1, C2, C3, D1, D2, and D3. GRα-B is not produced in the Guinea Pig. Total GR antibody identified 10 specific bands from term (n = 29) and preterm pregnancies (n = 27). Known isoforms included GRγ, GRα A, GRβ, GRP, GRA and GRα D1-3. There were sex and gestational age differences in placental GR isoform expression. Placental GRα A was detected in the cytoplasm of all groups but was significantly increased in the cytoplasm and nucleus of preterm males and females exposed to betamethasone and untreated term males (KW-ANOVA, P = 0.0001, P = 0.001). Cytoplasmic expression of GRβ was increased in female preterm placentae and preterm and term male placentae exposed to betamethasone (P = 0.01). Nuclear expression of GRβ was increased in all placentae exposed to betamethasone (P = 0.0001). GRα D2 and GRα D3 were increased in male preterm placentae when exposed to betamethasone (P = 0.01, P = 0.02). The current data suggests the sex-specific placental response to maternal betamethasone may be dependent on the expression of a combination of GR isoforms.
authors: Mater Medical Research Institute, University of Queensland, Brisbane, Qld, Australia.|Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
authors: Zarqa
authors: Z
authors: Saif
authors: Mothers and Babies Research Centre; Hunter Medical Research Institute, New Lambton Heights, NSW, 2305, Australia; and Faculty of Health, University of Newcastle, Callaghan, NSW, 2308, Australia.|Graduate School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.
authors: Rebecca M
authors: RM
authors: Dyson
authors: Mothers and Babies Research Centre; Hunter Medical Research Institute, New Lambton Heights, NSW, 2305, Australia; and Faculty of Health, University of Newcastle, Callaghan, NSW, 2308, Australia.
authors: Hannah K
authors: HK
authors: Palliser
authors: Mothers and Babies Research Centre; Hunter Medical Research Institute, New Lambton Heights, NSW, 2305, Australia; and Faculty of Health, University of Newcastle, Callaghan, NSW, 2308, Australia.|Graduate School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.
authors: Ian M R
authors: IM
authors: Wright
authors: Division of Allergy-Immunology, Department of Medicine, Northwestern University, Chicago, IL, United States of America.
authors: Nick
authors: N
authors: Lu
authors: Mater Medical Research Institute, University of Queensland, Brisbane, Qld, Australia.|Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
authors: Vicki L
authors: VL
authors: Clifton
mesh_terms: D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D005260:Female; D047109:Fetal Development; D005865:Gestational Age; D006168:Guinea Pigs; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis* / Q000235:genetics; D012737:Sex Factors; D047929:Term Birth / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D001623:Betamethasone