Sex Steroids and Growth Factors Differentially Regulate the Growth and Differentiation of Cultured Human Endometrial Stromal Cells*

Irwin, Juan C.; Utian, Wulf H.; Eckert, Richard L.

doi:10.1210/endo-129-5-2385

Cited by 217 publications

(116 citation statements)

References 37 publications

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“…Results from various studies provide abundant evidence that relaxin is a potent regulator of the differentiated function of human endometrial cells in vitro (14,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Relaxin stimulates the production of prolactin (16,17,19), insulin-like growth factor (18), and insulin-like growth factor binding protein 1 (IGFBP-1) (19), in progestin-primed endometrial stromal cells.…”

Section: Discussionmentioning

confidence: 99%

“…Relaxin stimulates the production of prolactin (16,17,19), insulin-like growth factor (18), and insulin-like growth factor binding protein 1 (IGFBP-1) (19), in progestin-primed endometrial stromal cells. Because prolactin and IGFBP-1 are considered the major secretory proteins of decidual cells (21), induction of the expression of these secretory proteins has been widely used as a biochemical marker of decidualization of endometrial stromal cells in vitro (22). Detailed studies of the regulation of IGFBP-1 promoter activity in endometrial stromal cells demonstrate that relaxin, not progesterone, is the major inducer of IGFBP-1 gene transcription (20).…”

Section: Discussionmentioning

confidence: 99%

“…A role for relaxin in human endometrial function is also supported by findings that relaxin binds specifically and with high affinity to human endometrial cells (15). In addition, a large body of evidence exists to demonstrate that relaxin has definitive effects on human endometrial cells in vitro (14,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Relaxin stimulates production of several endometrial products including prolactin, glycodelin, insulin-like growth factor binding protein 1 (IGFBP-1) and vascular endothelial growth factor in progestin-primed human endometrial cells in vitro.…”

mentioning

confidence: 99%

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Relaxin regulation of endometrial structure and function in the rhesus monkey

Goldsmith

Weiss

Palejwala

et al. 2004

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

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Despite the documented importance of the protein hormone relaxin in reproduction in various mammalian species, the role of relaxin in human reproduction is poorly understood, largely because of the lack of studies in women or in suitable non-human primate models. Here we describe the establishment of a nonhuman primate model of early human pregnancy and its use in defining the actions of relaxin. Results demonstrate that relaxin exerts dramatic uterine effects including pronounced increase in uterine weight and stimulation of endometrial angiogenesis and resident endometrial lymphocyte number. In addition, relaxin decreases endometrial levels of matrix metalloproteinases 1 and 3 and increases levels of their endogenous inhibitor, tissue inhibitor of metalloproteinase 1, resulting in maintenance of endometrial collagen content. Relaxin significantly inhibits endometrial levels of estrogen receptor ␣, but not ␤, and of progesterone receptor isoforms A and B. The findings that relaxin stimulates new blood vessel formation and increases cytokine-containing lymphocyte number while maintaining endometrial connective tissue integrity are consistent with a significant role of relaxin in the establishment and͞or maintenance of early pregnancy.R elaxin is a 6-kDa protein hormone member of the insulinlike growth factor family present in circulation in women during the latter part of the menstrual cycle and throughout pregnancy (1). In many mammalian species, relaxin exerts pronounced effects on the female reproductive tract that are involved in the maintenance of pregnancy and successful parturition (2, 3). Relaxin is important for normal delivery in several mammalian species because of its marked rearrangement of reproductive tract connective tissue (2-4). Despite the documented importance of relaxin in various mammalian species, the role of relaxin in human reproduction is, to date, an important, yet unanswered, question. Elucidation of the role of relaxin in women has been hampered by the inability to perform studies in women and by the lack of studies performed in suitable primate models of human pregnancy. Here we describe the establishment of a non-human primate model of early human pregnancy and its use in defining the actions of relaxin. Results demonstrate that relaxin exerts dramatic uterine effects including pronounced increase in uterine weight, stimulation of endometrial angiogenesis and resident lymphocyte number, maintenance of endometrial connective tissue integrity, and inhibition of endometrial estrogen and progesterone action. These effects are the developmental changes that occur in the human uterus during the late secretory phase of the menstrual cycle and early pregnancy. These findings support the thesis that relaxin acts as an important factor in uterine accommodation to and maintenance of early pregnancy in women.The dramatic species differences in the sources, secretion patterns, and target organs of relaxin have contributed greatly to the lack of understanding of the role of relaxin in human repr...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Relaxin regulation of endometrial structure and function in the rhesus monkey

Goldsmith

Weiss

Palejwala

et al. 2004

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

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“…TGFα and EGF are produced by the human endometrium across the menstrual cycle and by the decidua henceforth, and both act via paracrine and autocrine mechanisms to regulate endometrial growth (1,2,(4)(5)(6). Immunoreactive TGFα has been detected in the luminal surface epithelium of endometrial samples during all phases of menstrual cycle, but a diminished expression has been observed during the midsecretory phase (7).…”

Section: Department Of Obstetrics and Gynecology Universidadementioning

confidence: 99%

“…In spite of increasing evidence that estradiol and progesterone interact with EGF and TGFα to stimulate cell proliferation in mouse (6,13) and human (1,14) uterine tissues, the effect of sex steroid hormones on endometrial expression of these growth factors has not been assessed by controlled clinical trials in vivo.…”

Section: Department Of Obstetrics and Gynecology Universidadementioning

confidence: 99%

In Vivo Assessment of the Regulation of Transforming Growth Factor Alpha, Epidermal Growth Factor (EGF), and EGF Receptor in the Human Endometrium by Medroxyprogesterone Acetate

Reis

Lhullier

Edelweiss

et al. 2005

J Assist Reprod Genet

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Purpose : The present study evaluated the in vivo effect of medroxyprogesterone acetate (MPA) on the localization of immunoreactive transforming growth factor alpha (TGFα), epidermal growth factor (EGF), and their common receptor (EGF-R) in the human endometrium. Methods : The study design was a randomized clinical trial enrolling 36 healthy women with regular menstrual cycles. The participants were randomly assigned into three groups: groups 1 (n = 11) and 2 (n = 17) received placebo and were submitted to endometrial biopsy during the proliferative and secretory phases of menstrual cycle, respectively; group 3 (n = 8) received MPA (10 mg/day) for 10 days followed by endometrial biopsy, which was performed during the secretory phase. Immunohistochemistry was used to localize TGFα, EGF, and EGF-R in the endometrial tissue. Results : TGFα was present markedly in the luminal and glandular epithelia but also in the periglandular stroma, with a distribution pattern similar in the three experimental groups. EGF immunostaing was equally distributed in epithelial and stromal layers of the endometrium and remained unchanged in endometrial samples from women treated with MPA compared to placebo. EGF-R was expressed only in the epithelium. The intensity of EGF-R immunostaining was higher in secretory than in proliferative endometrium and was further increased by administration of MPA (p < 0.05, chi-square test). Conclusion : The present results suggest that the progestogen-induced in vivo differentiation of secretory endometrium does not require dramatic changes in the expression of EGF or TGFα, whereas EGF-R may be up regulated.

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CD44 expression in normal, hyperplastic, and malignant endometrium

1998

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A total of 140 endometrial carcinomas (endometrioid type), as well as 72 hyperplasias (41 of simple or complex and 31 of atypical type) and 141 normal endometria (35 in the proliferative and 106 in the secretory phase), were immunohistochemically investigated for expression of the standard and variant‐3 and ‐6 isoforms of CD44, and the results compared with several known prognostic factors. A combination of the reverse transcription‐polymerase chain reaction (RT‐PCR) and Southern blot hybridization (SBH) for CD44 mRNA levels was also carried out on 27 endometrial carcinomas. In normal endometrium, the expression of standard and variant CD44 forms was remarkably higher in the secretory than in the proliferative phase, with immunoreactivity scores being inversely correlated with numbers of oestrogen and progesterone receptors. Significantly elevated levels of CD44 expression in endometrial carcinomas compared with the proliferative phase and hyperplasia were also revealed by both the immunohistochemical and the RT‐PCR/SBH assays, while no association was noted with any prognostic factors. The results indicate that CD44 expression in the normal menstrual cycle is closely related to the secretory differentiation of the glandular epithelium. Moreover, detection of aberrant expression may be useful for the early diagnosis of endometrial carcinoma, but not as an indicator of tumour progression. © 1998 John Wiley & Sons, Ltd.

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Sex Steroids and Growth Factors Differentially Regulate the Growth and Differentiation of Cultured Human Endometrial Stromal Cells*

Cited by 217 publications

References 37 publications

Relaxin regulation of endometrial structure and function in the rhesus monkey

Relaxin regulation of endometrial structure and function in the rhesus monkey

In Vivo Assessment of the Regulation of Transforming Growth Factor Alpha, Epidermal Growth Factor (EGF), and EGF Receptor in the Human Endometrium by Medroxyprogesterone Acetate

CD44 expression in normal, hyperplastic, and malignant endometrium

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