Estrogen-regulated prohibitin is required for mouse uterine development and adult function

Bin He, Tae Hoon Kim, Ramakrishna Kommagani, Qin Feng, Rainer B. Lanz, Jae Wook Jeong, Francesco J. DeMayo, Benita S Katzenellenbogen, John P. Lydon, Bert W. O'Malley

Research output: Contribution to journalArticle

Abstract

Estrogen signaling is pivotal for maintenance of female reproductive function in mammals. The physiological role of estrogen is mediated by estrogen receptors (ERs) and the steroid receptor coactivator family of transcriptional coregulators. Ablation of steroid receptor coactivator and ER coactivators in mice causes impaired female reproductive function. Recently we reported that prohibitin (PHB) can function as a corepressor for ERs in cultured cells. In this study, we demonstrate that PHB is a nestrogen-regulated gene in vitro and in vivo, and its expression is induced by estrogen in the uterus, suggesting the existence of feedback regulatory loops. A conditional PHB knockout mouse model was generated by gene targeting to assess its in vivo function. Female mice with selective ablation of the PHB allele in the uterus were sterile, and their uteri were severely hypoplastic, indicating PHB is required for uterine development. Moreover, expression of ER and progesterone receptor target genes was selectively altered in response to hormone treatment. In summary, this study demonstrates that PHB is an estrogen-regulated gene and that PHB is essential for mouse uterine development and adult function and selectively required for estrogen-regulated gene expression.

Original languageEnglish (US)
Pages (from-to)1047-1056
Number of pages10
JournalEndocrinology
Volume152
Issue number3
DOIs
StatePublished - Mar 1 2011

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Estrogens
Estrogen Receptors
Uterus
Steroid Receptors
Genes
Co-Repressor Proteins
Gene Targeting
Progesterone Receptors
prohibitin
Knockout Mice
Mammals
Cultured Cells
Alleles
Maintenance
Hormones
Gene Expression

ASJC Scopus subject areas

  • Endocrinology

Cite this

He, B., Kim, T. H., Kommagani, R., Feng, Q., Lanz, R. B., Jeong, J. W., ... O'Malley, B. W. (2011). Estrogen-regulated prohibitin is required for mouse uterine development and adult function. Endocrinology, 152(3), 1047-1056. https://doi.org/10.1210/en.2010-0732

Estrogen-regulated prohibitin is required for mouse uterine development and adult function. / He, Bin; Kim, Tae Hoon; Kommagani, Ramakrishna; Feng, Qin; Lanz, Rainer B.; Jeong, Jae Wook; DeMayo, Francesco J.; Katzenellenbogen, Benita S; Lydon, John P.; O'Malley, Bert W.

In: Endocrinology, Vol. 152, No. 3, 01.03.2011, p. 1047-1056.

Research output: Contribution to journalArticle

He, B, Kim, TH, Kommagani, R, Feng, Q, Lanz, RB, Jeong, JW, DeMayo, FJ, Katzenellenbogen, BS, Lydon, JP & O'Malley, BW 2011, 'Estrogen-regulated prohibitin is required for mouse uterine development and adult function', Endocrinology, vol. 152, no. 3, pp. 1047-1056. https://doi.org/10.1210/en.2010-0732
He B, Kim TH, Kommagani R, Feng Q, Lanz RB, Jeong JW et al. Estrogen-regulated prohibitin is required for mouse uterine development and adult function. Endocrinology. 2011 Mar 1;152(3):1047-1056. https://doi.org/10.1210/en.2010-0732
He, Bin ; Kim, Tae Hoon ; Kommagani, Ramakrishna ; Feng, Qin ; Lanz, Rainer B. ; Jeong, Jae Wook ; DeMayo, Francesco J. ; Katzenellenbogen, Benita S ; Lydon, John P. ; O'Malley, Bert W. / Estrogen-regulated prohibitin is required for mouse uterine development and adult function. In: Endocrinology. 2011 ; Vol. 152, No. 3. pp. 1047-1056.
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