Binding of 125I-epidermal growth factor in human uterus

Chegini, Nasser; Rao, Ch.V.; Wakim, Najib G.; Sanfilippo, Joseph S.

doi:10.1007/bf00215194

Cited by 68 publications

(31 citation statements)

References 20 publications

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“…DNA synthesis was also observed in the endothelial cells of uterine blood vessels. The response of multiple uterine cell types to EGF is consistent with studies demonstrating that all uterine cell types contain EGF binding sites, thereby suggesting that all of the cell types may be potential targets of EGF action (13). However, EGF at the dose used here did not significantly stimulate DNA synthesis in liver, kidney, duodenum, lung, or mammary gland.…”

Section: Resultssupporting

confidence: 74%

Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation.

Nelson

Takahashi

Bossert

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

360

167

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The in vivo studies presented here demonstrate that epidermal growth factor (EGF) is an important autocrine and/or paracrine mediator of estrogen-induced growth and differentiation in mouse uterus and vagina. An antibody specific for EGF significantly inhibited estrogeninduced uterine and vaginal growth, thereby implicating EGF involvement in estrogen action. Furthermore, EGF administered via slow-release pellets in ovariectomized mice acted as a potent uterine and vaginal mitogen as well as an inducer of vaginal keratinization. Experiments with ovariectomized, adrenalectomized, hypophysectomized mice indicated that EGF mitogenesis does not require pituitary or adrenal hormones. Treatment with EGF also mimicked estrogen in the induction of uterine lactoferrin (a major estrogen-inducible secretory protein) mRNA and protein. These data suggest that EGF has estrogen-like effects in the promotion of cell growth in the reproductive tract and that EGF may serve as an important mediator of estrogen action in vivo.Estrogen-induced growth of various target tissues is mediated, in part, by the production of polypeptide growth factors, which may act in an autocrine or paracrine fashion to stimulate proliferation (1, 2). Two polypeptide growth factors, insulin-like growth factor I and epidermal growth factor (EGF), have been associated with the induction of uterine growth by estrogen (2, 3). Our laboratory and others have demonstrated that immunoreactive EGF precursor is present in the mouse uterus (3, 4), that estrogen treatment enhances the expression of EGF (3, 4) and EGF receptor (5) in the uterus, and that EGF is a potent mitogen in mouse uterine cell cultures (6). These studies provide evidence suggesting that EGF plays an important role in estrogen-induced uterine growth.Previous studies (3, 6) suggesting that EGF plays a role in uterine growth led us to further evaluate the role of EGF as a potential regulator of reproductive-tract growth in vivo. In this study, we demonstrate that estrogen action is inhibited by an EGF-specific antibody and that in vivo exposure to EGF alone mimics estrogen in the induction of uterine and vaginal growth and differentiation. Our results strongly suggest that EGF acts as an estrogen-inducible physiological mediator of mouse reproductive-tract growth in vivo. MATERIALS AND METHODS Quantitation of Uterine and Vaginal Growth FollowingExposure to an EGF-Specific Antibody. To determine whether an antibody specific for EGF could inhibit estrogen-induced growth, slow-release cholesterol-based pellets containing an antibody against EGF (whole antiserum; 2.5 mg per pellet; Collaborative Research) were prepared by Innovative Research of America. These pellets were divided into fourths and one quarter was implanted under the kidney capsule of 8-week-old female CD-1 mice that had been ovariectomized for at least 3 weeks. Appropriate control pellets containing normal whole serum (rabbit; 2.9 mg per pellet; Calbiochem) were also implanted. Three days following pellet implantation, the anim...

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Section: Resultssupporting

confidence: 74%

Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation.

Nelson

Takahashi

Bossert

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

360

167

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“…Although the levels of EGF receptors are not significantly higher in leiomyomas than in the myometrium and do not seem to fluctuate during the menstrual cycle (Chegini et al 1986;Hofmann et al 1984;Lumsden et al 1988), there is a sharp reduction of EGF-receptor levels in the leiomyomas but not in the myometrium of women treated with GnRH agonists prior to surgery (Lumsden et al 1988). These data suggest that the EGF receptors in fibroids are more sensitive to regulation by the ovarian sex steroids than those in the myometrium.…”

Section: Growth Factors Identified In Fibroidsmentioning

confidence: 73%

Etiology and pathogenesis of uterine leiomyomas: a review.

Flake

Andersen

Dixon

2003

Environ Health Perspect

497

392

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Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor-β 3, basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.

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“…Numerous workers have identified high and low affinity PGE2 and PGF2, binding sites on the human myometrium (Wakeling & Wyngarden, 1974;Crankshaw et al, 1979;Bauknecht et al, 1981;Giannopoulos et al, 1985;Chegini et al, 1986;Adelantado et al, 1988). Hofmann et al (1983) and Giannopoulos et al (1985) began to elucidate PGE and PGF2, receptor topography in the human uterus.…”

Section: Introductionmentioning

confidence: 99%

In vitro characterization of prostanoid receptors on human myometrium at term pregnancy

Senior

Marshall

Sangha

et al. 1993

British J Pharmacology

211

110

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Postgraduate Studies in Pharmacology, University of Bradford, Bradford BD7 1DP and *The Royal Infirmary, Bradford BD9 6RJ1 Prostanoid receptors present on the pregnant human myometrium in vitro have been characterized according to the receptor classification proposed by Coleman et al. (1984) using natural prostanoids and synthetic, selective analogues and antagonists where available. 2 Prostaglandin E2 (PGE2) produced a biphasic effect consisting of an initial excitation followed by a dose-related inhibition. The EP2/EP3-receptor agonists, rioprostil and misoprostol, produced similar effects to PGE2, however, the excitatory event of the misoprostol response was related to dose. The EPI/EP3-receptor agonist, sulprostone, evoked a purely excitatory response which was unaffected by AH6809. The selective EP2-receptor agonist butaprost produced a long-lasting dose-dependent inhibition of activity. The results from these prostanoids indicated that inhibitory EP2-and excitatory EP3-receptors are present on myometrium from pregnant donors at term.3 PGF2,, and the synthetic FP-receptor agonist, fluprostenol, caused equipotent excitatory effects, indicating the presence of contractile FP-receptors. 4 PGD2 produced a biphasic effect of which the inhibition appeared dose-related and was antagonized by the selective DP-receptor antagonist BW A868C. The selective DP-receptor agonist, BW245C, produced a potent inhibitory effect that was competitively antagonized by BW A868C (pA2= 8.6).5 PGI2 produced a biphasic response qualitatively similar to PGE2. The EP,/IP-receptor agonist, iloprost, produced an occasional unquantifiable excitation and dose-related inhibition. The selective IP-receptor prostanoid, cicaprost, evoked only an inhibitory response. 6 The stable thromboxane A2 (TXA2)-mimetic, U46619, produced potent excitation which was competitively antagonized by the TP-receptor antagonist, GR32191 (pA2 = 7.2). 7 The prostanoids tested indicate that a heterogeneous population of prostanoid receptors are present on human myometrium from pregnant donors. It may be concluded that excitation is EP3-, FP-and TP-receptor-mediated and inhibition is EP2-, DP-and IP-receptor-mediated. Comparison of data obtained from non-pregnant specimens indicates that the lower segment tissue from pregnant donors demonstrated more pronounced responses to EP2 and IP-receptor activation.

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Binding of 125I-epidermal growth factor in human uterus

Cited by 68 publications

References 20 publications

Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation.

Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation.

Etiology and pathogenesis of uterine leiomyomas: a review.

In vitro characterization of prostanoid receptors on human myometrium at term pregnancy

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