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Gestational Changes in the Levels of Transforming Growth Factor-ß1 (TGFß1) and TGFß Receptor Types I and II in the Human Myometrium¹

Departments of Surgical Sciences (J.I.G.) and Obstetrics and Gynecology, The Medical School, University of Newcastle upon Tyne, United Kingdom NE2 4HH

Address all correspondence and requests for reprints to: Dr. James I. Gillespie, Departments of Physiological Sciences and Obstetrics and Gynecology, The Medical School, The University, United Kingdom NE2 4HH. E-mail: j.i.gillespie{at}ncl.ac.uk

As term approaches, a number of key proteins [contraction-associated proteins (CAPs)] are expressed within the human myometrium that are essential for the activation of powerful coordinated contractions during labor. The nature of the signals that switch on the synthesis of CAPs in vivo is not known. The ryanodine-sensitive intracellular Ca²⁺ release channel (RyR2) is a CAP whose expression in vitro is activated by transforming growth factor-ß (TGFß). The present experiments were performed to determine whether TGFß and TGFß receptors are present in the human myometrium at term and to explore the idea that they might form part of a signaling system in vivo. TGFß receptor types I and II, but not III, were demonstrated in myometrial smooth muscle in tissue taken from nonpregnant, pregnant nonlaboring, and spontaneous laboring women. Western blotting was used subsequently to determine the relative expression of TGFß receptor types I and II. Using nonpregnant myometrium as a baseline control the levels of expression of receptor types I and II were significantly increased by 168 ± 19% (n = 6) and 162 ± 22% (n = 7) in pregnant nonlaboring myometrium. In spontaneous laboring myometrium the levels of TGFß receptor type I and II expression were 93 ± 12% (n = 6) and 85 ± 11% (n = 7), respectively, compared to nonpregnant control values and were significantly lower than levels in pregnant nonlaboring tissues. The total TGFß1 levels in the myometrial tissues were 334 ± 10, 534 ± 73, and 674 ± 106 pg/g tissue wet wt in nonpregnant, pregnant nonlaboring, and spontaneous laboring myometrium (n = 3 in each group), respectively. Thus, the TGFß signaling system appears to be up-regulated in the myometrium before the onset of parturition. The apparent loss of receptors in the spontaneous laboring samples in the presence of elevated total levels of TGFß may be indicative of agonist-induced receptor down-regulation. These observations support the idea that cytokines, in particular TGFß1, may play a role in the normal processes that prepare the myometrium for parturition at term.

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