Human Endometrial Transforming Growth Factor-α: A Transmembrane, Surface Epithelial Protein That Transiently Disappears During the Midsecretory Phase of the Menstrual Cycle

Hansard, L.J.; Healy-Gardner, Bridget E.; Drapkin, Annie T.; Bentley, Rex C.; McLachlan, John A.; Walmer, David K.

doi:10.1177/107155769700400308

Cited by 9 publications

(12 citation statements)

References 29 publications

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“…This observation comes from prospective, randomized administration of a very specific progesterone receptor agonist, MPA, to healthy voluntaries during the luteal phase of menstrual cycle, and does not support the findings of previous observational studies (7,17) showing that TGFα expression was lower in secretory than in proliferative endometrium. In the current study, the administration of an exogenous progestogen created the opportunity to observe the endometrial response to a homogeneous progesterone-like stimulation, which is difficult to obtain in spontaneous cycles due to interindividual variability of progesterone levels.…”

Section: Discussioncontrasting

confidence: 89%

“…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). A possible cyclic variation in the expression of EGF and EGF-R in the endometrium is controversial, being observed (8-10) or not (4,11,12) in different studies.…”

Section: Department Of Obstetrics and Gynecology Universidadementioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 89%

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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“…In human colon extract ( Figure 3B, Lane 5), apart from the presence of the immunoglobulin IgG 2a light chain (around 30 kD) and heavy chain (around 50 kD), which correspond to the bands of the normal mouse IgG 2a control ( Figure 3B, Lane 10), there was a band of around 25-28 kD. This 25-28-kD band, also seen in some previous studies (Hansard et al 1997;Hoffmann et al 1997;Wang et al 1997), could be assumed to be a TGF-␣ precursor. After human colon was fixed in either formalin (Figure 3B, Lane 8) or in Methacarn ( Figure 3B, Lane 9) and processed for paraffin embedding, the immunoreactive material in the protein extracts by this monoclonal antibody appeared to be around 31 and 66 kD in size, the identities of which remain to be determined.…”

Section: Western Immunoblotting For Antibody Specificity Analysismentioning

confidence: 62%

“…The two larger molecular species probably represent precursor peptides of TGF-␣ which were also shown in some previous studies (Hansard et al 1997;Hoffmann et al 1997;Tureaud et al 1997;Wang et al 1997). Using this antibody, no TGF-␣ immunoreactivity was found in colon protein samples from knockout mice ( Figure 3A, Lane 4), but one band of around 25-28 kD was revealed in the sample from wild-type mice ( Figure 3A, Lane 5).…”

Section: Western Immunoblotting For Antibody Specificity Analysismentioning

confidence: 78%

Specificity of the Localization of Transforming Growth Factor-α Immunoreactivity in Colon Mucosa

Chen

Mardell

Read

1999

J Histochem Cytochem.

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SUMMARY Transforming growth factor-␣ (TGF-␣ ) plays an important role in gastrointestinal pathophysiology. However, the exact location of its expression in the intestine is still controversial. This study systematically compared the localization of TGF-␣ immunoreactivity in frozen or fixed human colon using three different antibodies and examined specificity of antibodies by using tissues from TGF-␣ knockout mice and by Western blotting. Consistent with the mRNA distribution revealed by in situ hybridization, a similar staining pattern was obtained in frozen sections by all three antibodies, localizing on the surface and along the crypt epithelium. In paraffin sections, although the polyclonal antibodies (raised against recombinant human or rat TGF-␣ ) gave minimal staining, the monoclonal antibody (against C-terminal peptide of human TGF-␣ ) still gave intense staining on the surface and upper crypt epithelium. By using specimens from TGF-␣ knockout mice in immunostaining and Western blotting, the polyclonal antibodies were shown to be specific. In contrast, specificity of the monoclonal antibody was in doubt in rodent tissues because it gave similar detection between wild-type and knockout mice in both analyses, indicating its crossreaction to non-TGF-␣ molecules. In conclusion, frozen sections and antibodies raised from recombinant TGF-␣ should be used for TGF-␣ immunohistochemistry in the colon. (J Histochem Cytochem 47:949-957, 1999)

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“…This endometrial TGF␣ expression is temporally coupled with a corresponding rise in blastocyst expression of EGFR [3,4] and the preferential localization of functional EGFR on the basolateral surface of the blastocyst trophectoderm [5]. Evidence that TGF␣/EGFR signaling may be important in the human includes the observation of persistent expression of EGFR mRNA in the polar trophectoderm of human blastocysts into the periimplantation time frame [6], the immunolocalization of EGFR in human implantation trophoblast [7], and the cyclic changes of TGF␣ expression in the endometrial surface epithelium during the secretory phase of the menstrual cycle when embryos are present in the uterus [8].…”

Section: Introductionmentioning

confidence: 99%

Evidence of Juxtacrine Signaling for Transforming Growth Factor α inHuman Endometrium1

Bush

Mele

Couchman

et al. 1998

Biology of Reproduction

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To determine the mechanism of signaling for transforming growth factor alpha (TGFalpha) in human endometrium, uterine luminal fluid proteins were retrieved by lavage followed by collection of the adjacent endometrium at hysterectomy. In the endometrium we observed the presence of the full-length transmembrane TGFalpha protein and the phosphorylation of its only known receptor, the epidermal growth factor receptor (EGFR), by immunoprecipitation-Western blot; TGFalpha mRNA via reverse transcription-polymerase chain reaction; and immunolocalization of TGFalpha to the surface endometrium adjacent to the uterine lumen. Despite this demonstration of TGFalpha in functional endometrium, we could not detect measurable amounts of TGFalpha in any of the 16 endometrial washings by either immunoprecipitation-Western blot or by ELISA. Recovery rate for intraluminal fluid spiked with TGFalpha control peptide was 93.4-97%. The inability to detect TGFalpha in intraluminal fluid despite its high concentration in cells directly adjacent to the uterine lumen, along with the absence of any cleaved TGFalpha species identified in the endometrium, suggests that TGFalpha signals its receptor as a transmembrane ligand. Since the EGFR is present in the endometrium and on the surface of embryos, these data are consistent with a juxtacrine mode of signaling for TGFalpha between endometrial cells, and between the luminal surface epithelium and preimplantation embryos.

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Human Endometrial Transforming Growth Factor-α: A Transmembrane, Surface Epithelial Protein That Transiently Disappears During the Midsecretory Phase of the Menstrual Cycle

Cited by 9 publications

References 29 publications

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

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

Specificity of the Localization of Transforming Growth Factor-α Immunoreactivity in Colon Mucosa

Evidence of Juxtacrine Signaling for Transforming Growth Factor α inHuman Endometrium1

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