Stefan Andersson1, Debra Minjarez, Nicole P Yost, R Ann Word. 1. Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032, USA.
Abstract
CONTEXT: Experimental and clinical studies in a variety of nonprimate species demonstrate that progesterone withdrawal leads to changes in gene expression that initiate parturition at term. Mice deficient in 5alpha-reductase type I fail to undergo cervical ripening at term despite the timely onset of luteolysis and progesterone withdrawal in blood. OBJECTIVE: Our objective was to test the hypothesis that estrogen and progesterone metabolism is regulated in cervical tissues during pregnancy, even in species in which parturition is not characterized by progesterone withdrawal in blood. DESIGN: Estradiol and progesterone metabolism was quantified in intact cervical tissues from nonpregnant and pregnant women at term before or after labor. SETTING: The study was conducted at a university hospital. PATIENTS: Tissues were obtained from five nonpregnant and 21 pregnant women (nine before labor and 12 in labor). MAIN OUTCOME MEASURES: Enzyme activity measurements, Northern blot analysis, quantitative real-time RT-PCR, and immunohistochemistry were used to quantify steroid hormone metabolizing enzymes in cervical and myometrial tissues. RESULTS: During pregnancy, 17beta-hydroxysteroid dehydrogenase type 2 was induced in glandular epithelial cells to catalyze the conversion of estradiol to estrone and stroma-derived 20alpha-hydroxyprogesterone to progesterone. During parturition, 17beta-hydroxysteroid dehydrogenase type 2 was down-regulated in endocervical cells, thereby creating a microenvironment favorable for cervical ripening. CONCLUSIONS: Together, the data indicate that cervical ripening during parturition involves localized regulation of estrogen and progesterone metabolism through a complex relationship between cervical epithelium and stroma, and that steroid hormone metabolism in cervical tissues from pregnant women is unique from that in mice.
CONTEXT: Experimental and clinical studies in a variety of nonprimate species demonstrate that progesterone withdrawal leads to changes in gene expression that initiate parturition at term. Mice deficient in 5alpha-reductase type I fail to undergo cervical ripening at term despite the timely onset of luteolysis and progesterone withdrawal in blood. OBJECTIVE: Our objective was to test the hypothesis that estrogen and progesterone metabolism is regulated in cervical tissues during pregnancy, even in species in which parturition is not characterized by progesterone withdrawal in blood. DESIGN:Estradiol and progesterone metabolism was quantified in intact cervical tissues from nonpregnant and pregnant women at term before or after labor. SETTING: The study was conducted at a university hospital. PATIENTS: Tissues were obtained from five nonpregnant and 21 pregnant women (nine before labor and 12 in labor). MAIN OUTCOME MEASURES: Enzyme activity measurements, Northern blot analysis, quantitative real-time RT-PCR, and immunohistochemistry were used to quantify steroid hormone metabolizing enzymes in cervical and myometrial tissues. RESULTS: During pregnancy, 17beta-hydroxysteroid dehydrogenase type 2 was induced in glandular epithelial cells to catalyze the conversion of estradiol to estrone and stroma-derived 20alpha-hydroxyprogesterone to progesterone. During parturition, 17beta-hydroxysteroid dehydrogenase type 2 was down-regulated in endocervical cells, thereby creating a microenvironment favorable for cervical ripening. CONCLUSIONS: Together, the data indicate that cervical ripening during parturition involves localized regulation of estrogen and progesterone metabolism through a complex relationship between cervical epithelium and stroma, and that steroid hormone metabolism in cervical tissues from pregnant women is unique from that in mice.
Authors: E A DeFranco; J M O'Brien; C D Adair; D F Lewis; D R Hall; S Fusey; P Soma-Pillay; K Porter; H How; R Schakis; D Eller; Y Trivedi; G Vanburen; M Khandelwal; K Trofatter; D Vidyadhari; J Vijayaraghavan; J Weeks; B Dattel; E Newton; C Chazotte; G Valenzuela; P Calda; M Bsharat; G W Creasy Journal: Ultrasound Obstet Gynecol Date: 2007-10 Impact factor: 7.299
Authors: Brian M McKeever; Barton K Hawkins; Wayne M Geissler; Ling Wu; Robert P Sheridan; Ralph T Mosley; Stefan Andersson Journal: Biochim Biophys Acta Date: 2002-11-19
Authors: Gemma Madsen; Tamas Zakar; Chun Ying Ku; Barbara M Sanborn; Roger Smith; Sam Mesiano Journal: J Clin Endocrinol Metab Date: 2004-02 Impact factor: 5.958
Authors: Sam Mesiano; Eng-Cheng Chan; John T Fitter; Kenneth Kwek; George Yeo; Roger Smith Journal: J Clin Endocrinol Metab Date: 2002-06 Impact factor: 5.958
Authors: Annavarapu Hari Kishore; Hanquan Liang; Mohammed Kanchwala; Chao Xing; Thota Ganesh; Yucel Akgul; Bruce Posner; Joseph M Ready; Sanford D Markowitz; Ruth Ann Word Journal: Proc Natl Acad Sci U S A Date: 2017-07-17 Impact factor: 11.205
Authors: Steven M Yellon; Bryan T Oshiro; Tejas Y Chhaya; Thomas J Lechuga; Rejane M Dias; Alexandra E Burns; Lindsey Force; Ede M Apostolakis Journal: Biol Reprod Date: 2011-05-25 Impact factor: 4.285
Authors: Sam A Mesiano; Gregory A Peters; Peyvand Amini; Rachel A Wilson; Gregory P Tochtrop; Focco van Den Akker Journal: Placenta Date: 2019-01-28 Impact factor: 3.481
Authors: Ramkumar Menon; Elizabeth A Bonney; Jennifer Condon; Sam Mesiano; Robert N Taylor Journal: Hum Reprod Update Date: 2016-06-30 Impact factor: 15.610
Authors: G Chittoor; V S Farook; S Puppala; S P Fowler; J Schneider; T D Dyer; S A Cole; J L Lynch; J E Curran; L Almasy; J W Maccluer; A G Comuzzie; D E Hale; R S Ramamurthy; D J Dudley; E K Moses; R Arya; D M Lehman; C P Jenkinson; B S Bradshaw; R A Defronzo; J Blangero; R Duggirala Journal: Mol Hum Reprod Date: 2013-05-20 Impact factor: 4.025
Authors: Steven M Yellon; Alexandra E Burns; Jennifer L See; Thomas J Lechuga; Michael A Kirby Journal: Biol Reprod Date: 2009-02-18 Impact factor: 4.285