title: Lipogenesis impaired in periparturient rats exposed to altered gravity is independent of prolactin and glucocorticoid secretion.
abstract: Perturbed prolactin (PRL) secretion and concomitant downregulation of PRL receptor (PRLR) in periparturient dams exposed to altered gravity are linked to aberrant lipogenesis and reduced neonatal survival. PRL and glucocorticoids (GC) are known to modulate PRLR expression. We hypothesized that improving levels of PRLR would mitigate the increased gravity [hypergravity (HG)]-induced effects of impaired mammary lipogenesis and increase neonatal survival. The objective of this study was to determine if prepartum PRL or GC supplementation would override the HG-induced repression of PRLR along with lipogenic genes and increase tissue fatty acid synthesis. Pregnant rats were exposed to either 2g (HG) or kept at 1g (control) from day 11 of gestation (G11) through Postnatal day 1 (P1). HG exposed rats were supplemented with either PRL or corticosterone or a placebo from G13 to P1. On P1, mammary, liver and adipose tissues were collected to measure glucose incorporation into lipids and mRNA abundance of PRL long and short form receptors (Prlr-l, Prlr-s), glucocorticoid receptor (Nr3c1), Acetyl CoA carboxylase-alpha (Acaca), fatty acid synthase (Fasn), lipoprotein lipase (Lpl), Sterol Regulatory Element Binding Protein-1 (Srebp1) and protein kinase B (Akt1) genes by quantitative polymerase chain reaction (qPCR). PRL and GC supplementation had a limited effect on lipogenesis in the three tissues of HG group likely due to their inability to increase abundance of key down-regulated genes, including Prlr-l and Nr3c1. There was no difference in the abundance of genes coding for milk proteins or those associated with milk fat globule formation and secretion. These data suggest that reduced lipogenesis in HG exposed dams is independent of PRL and GC secretion but may be associated with dysregulation of multiple metabolic regulators at the level of mRNA expression.
authors.affiliation: Department of Animal Science, Michigan State University, B290 Anthony Hall, East Lansing, MI 48824, USA. patelo@msu.edu
authors.forename: Osman V
authors.initials: OV
authors.lastname: Patel
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Zakrzewska
authors.forename: Rhonda L
authors.initials: RL
authors.lastname: Maple
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Baer
authors.forename: April E
authors.initials: AE
authors.lastname: Ronca
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wade
authors.forename: Karen
authors.initials: K
authors.lastname: Plaut
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D018471:Hypergravity; D007774:Lactation / Q000235:genetics; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D010084:Oxidation-Reduction; D036801:Parturition; D011247:Pregnancy; D011388:Prolactin / Q000008:administration & dosage / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011981:Receptors, Prolactin / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011981:Receptors, Prolactin; D011388:Prolactin; D005947:Glucose; D003345:Corticosterone