Uterine and vaginal organ growth requires epidermal growth factor receptor signaling from stroma

Yun Kit Hom, Peter Young, Jane Wiesen, Päivi J. Miettinen, Rik Derynck, Zena Werb, Gerald R. Cunha

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Estrogens are crucial for growth and function of the female genital tract. Recently, we showed that induction of uterine epithelial proliferation by estradiol is a paracrine event requiring an estrogen receptor-positive stroma. Growth factors [such as EGF (epidermal growth factor) ligands] are likely paracrine mediators, which may directly or indirectly regulate epithelial proliferation in estrogen target organs via cell-cell interactions. In this report, we used mice with a null mutation in their EGF receptor (EGFR) to examine the role of EGFR signaling in growth of the uterus and vagina and in estrogen-induced uterine and vaginal epithelial proliferation. When WT and EGFR-knockout (EGFR-KO) uteri and vaginae were grown as renal capsule grafts in nude mice, growth of uterine and vaginal grafts of EGFR-KO mice was reduced, compared with their WT counterparts. Grafts of both EGFR-KO uteri and vaginae were about one third smaller (wet weight) than their corresponding WT organs, even though differentiation of both epithelium and mesenchyme were normal in both cases. Both wild-type and EGFR-KO vaginal grafts contained within their lumina alternating layers of cornified and mucified epithelial cell layers, indicating cyclic alteration of epithelial differentiation. In response to estradiol treatment, stromal cell labeling index (LI), as assessed by incorporation of 3H-thymidine, was severely depressed in EGFR-KO uterine and vaginal grafts vs. stromal cell LI in WT uterine and vaginal grafts. Unexpectedly, epithelium of both EGFR-KO and wild-type grafts responded comparably to estradiol with a marked elevation (~7-fold overall) of epithelial LI in response to estradiol in uterine and vaginal epithelia. These data supported the hypothesis that overall uterine and vaginal organ growth, in response to estrogen, required EGFR signaling for DNA synthesis in the fibromuscular stroma, whereas EGFR signaling was not essential for estrogen-induced epithelial growth in the uterus and vagina.

Original languageEnglish (US)
Pages (from-to)913-921
Number of pages9
JournalEndocrinology
Volume139
Issue number3
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Growth
Transplants
Vagina
Estrogens
Uterus
Estradiol
Epithelium
Stromal Cells
Mesoderm
Epidermal Growth Factor
Nude Mice
Cell Communication
Estrogen Receptors
Thymidine
Capsules
Intercellular Signaling Peptides and Proteins
Epithelial Cells
Ligands
Kidney

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Hom, Y. K., Young, P., Wiesen, J., Miettinen, P. J., Derynck, R., Werb, Z., & Cunha, G. R. (1998). Uterine and vaginal organ growth requires epidermal growth factor receptor signaling from stroma. Endocrinology, 139(3), 913-921. https://doi.org/10.1210/en.139.3.913

Uterine and vaginal organ growth requires epidermal growth factor receptor signaling from stroma. / Hom, Yun Kit; Young, Peter; Wiesen, Jane; Miettinen, Päivi J.; Derynck, Rik; Werb, Zena; Cunha, Gerald R.

In: Endocrinology, Vol. 139, No. 3, 1998, p. 913-921.

Research output: Contribution to journalArticle

Hom, YK, Young, P, Wiesen, J, Miettinen, PJ, Derynck, R, Werb, Z & Cunha, GR 1998, 'Uterine and vaginal organ growth requires epidermal growth factor receptor signaling from stroma', Endocrinology, vol. 139, no. 3, pp. 913-921. https://doi.org/10.1210/en.139.3.913
Hom, Yun Kit ; Young, Peter ; Wiesen, Jane ; Miettinen, Päivi J. ; Derynck, Rik ; Werb, Zena ; Cunha, Gerald R. / Uterine and vaginal organ growth requires epidermal growth factor receptor signaling from stroma. In: Endocrinology. 1998 ; Vol. 139, No. 3. pp. 913-921.
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