title: Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy.
abstract: During pregnancy, uterine smooth muscle (USM) coordinately adapts its contractile phenotype in order to accommodate the developing fetus and then prepare for delivery. Herein we show that SMTNL1 plays a major role in pregnancy to promote adaptive responses in USM and that this process is specifically mediated through interactions of SMTNL1 with the steroid hormone receptor PR-B. In vitro and in vivo SMTNL1 selectively binds PR and not other steroid hormone receptors. The physiological relationship between the two proteins was also established in global gene expression and transcriptional reporter studies in pregnant smtnl1(-/-) mice and by RNA interference in progesterone-sensitive cell lines. We show that the contraction-associated and progestin-sensitive genes (oxytocin receptor, connexin 43, and cyclooxygenase-2) and prolactins are down-regulated in pregnant smtnl1(-/-) mice. We suggest that SMTNL1 is a bifunctional co-regulator of PR-B signaling and thus provides a molecular mechanism whereby PR-B is targeted to alter gene expression patterns within USM cells to coordinately promote alterations in USM function during pregnancy.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Khaldon
authors.initials: K
authors.lastname: Bodoor
authors.forename: Beata
authors.initials: B
authors.lastname: Lontay
authors.forename: Rachid
authors.initials: R
authors.lastname: Safi
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Weitzel
authors.forename: David
authors.initials: D
authors.lastname: Loiselle
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Wei
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Lengyel
authors.forename: Donald P
authors.initials: DP
authors.lastname: McDonnell
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Haystead
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011372:Progestins; D011388:Prolactin; D011980:Receptors, Progesterone / Q000378:metabolism*; D014158:Transcription, Genetic; D000096985:Calponins
chemical_list: D009124:Muscle Proteins; D010750:Phosphoproteins; D011372:Progestins; D011388:Prolactin; D011980:Receptors, Progesterone; C491838:SMTNL1 protein, mouse; D000096985:Calponins