Leptin receptor expression in the rat placenta: changes in ob-ra, ob-rb, and ob-re with gestational age and suppression by glucocorticoids.
Leptin, the hormone product of the ob gene, has recently been implicated as an important player in the complex hormonal control of fetal growth. Leptin actions are mediated via the long isoform of its receptor (Ob-Rb), while shorter isoforms may serve as transporters of leptin through physiological barriers (Ob-Ra) or as leptin-binding proteins in plasma (Ob-Re). Placental expression of these receptor isoforms could thus mediate leptin actions within the placenta or regulate transport of maternal, placental, and fetal leptin. In the present study, we show by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) that Ob-Ra, Ob-Rb, and Ob-Re mRNAs are dynamically expressed in the functionally distinct basal and labyrinth zones of the rat placenta during the period of maximal fetal growth (i.e., from Day 16 to Day 22 of pregnancy; term = Day 23). Western blot analyses confirmed placental expression of the Ob-Rb protein, and immunolocalization was most prominent in trophoblast and vascular tissues of the labyrinth zone. Ob-Ra and Ob-Re mRNA expression increased markedly (P < 0.01) from Day 16 to Day 22 in the labyrinth but not in the basal zone, whereas Ob-Rb mRNA and protein remained relatively stable. Because glucocorticoids inhibit feto-placental growth, placental leptin receptor (Ob-R) expression was also measured after manipulation of feto-placental glucocorticoid exposure. Maternal treatment with dexamethasone reduced (P < 0.05) placental expression of Ob-Rb mRNA and protein, whereas metyrapone (an inhibitor of glucocorticoid synthesis) stimulated (P < 0.01) placental expression of mRNAs encoding all three Ob-R isoforms. Dexamethasone and carbenoxolone (an inhibitor of the enzyme 11beta-hydroxysteroid dehydrogenase) also markedly reduced (P < 0.01) fetal but not maternal plasma leptin concentrations, consistent with inhibition of transplacental passage of maternal leptin. In conclusion, our data indicate that placental expression of Ob-Ra, Ob-Rb, and Ob-Re is likely to mediate leptin action and transport in the fetus and placenta. The effects of glucocorticoid manipulations on placental expression of these isoforms suggest that glucocorticoid-induced feto-placental growth retardation could be mediated, in part, via inhibition of leptin action or transport in the placenta.
Smith
Jeremy T
JT
School of Anatomy and Human Biology and The Western Australian Institute for Medical Research, The University of Western Australia, Crawley, Perth, Australia.
Waddell
Brendan J
BJ
D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced; D015870:Gene Expression / Q000187:drug effects*; D005865:Gestational Age; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology*; D007150:Immunohistochemistry; D020738:Leptin / Q000097:blood; D008797:Metyrapone / Q000494:pharmacology; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics*; D054411:Receptors, Leptin; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D003907:Dexamethasone; D013252:Steroid 11-beta-Hydroxylase; D002229:Carbenoxolone; D008797:Metyrapone