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Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult.

Publication ,  Journal Article
Schomberg, DW; Couse, JF; Mukherjee, A; Lubahn, DB; Sar, M; Mayo, KE; Korach, KS
Published in: Endocrinology
June 1999

Targeted disruption of the mouse estrogen receptor-alpha gene (estrogen receptor-alpha knockout; ERKO) results in a highly novel ovarian phenotype in the adult. The ERKO mouse model was used to characterize ER alpha-dependent processes in the ovary. Visualization of the ovaries of 10-, 20-, and 50-day-old wild-type (WT) and ERKO mice showed that the ERKO phenotype developed between 20 and 50 days of age. Developmental progression through the primordial, primary, and antral follicle stages appeared normal, but functional maturation of preovulatory follicles was arrested resulting in atresia or in anovulatory follicles, which in many cases formed large, hemorrhagic cysts. Corpora lutea were absent, which also indicates that the normal biochemical and mechanical processes that accomplish ovulation were compromised. Northern and ribonuclease protection analyses indicated that ERKO ovary FSH receptor (FSHR) messenger RNA (mRNA) expression was approximately 4-fold greater than in WT controls. Ovarian LH receptor (LHR) mRNA expression was also higher in the ERKO animals. Cellular localization studies by in situ hybridization analysis of ERKO ovaries showed a high level of LHR mRNA expression in the granulosa and thecal layers of virtually all the antral follicles. Ribonuclease protection analyses showed that ovarian progesterone receptor and androgen receptor mRNA expression were similar in the two groups. These results indicated that ER alpha action was not a prerequisite for LHR mRNA expression by thecal or granulosa cells or for ovarian expression of progesterone receptor mRNA. Ovarian estrogen receptor beta (ER beta) was detected immunohistochemically, was sharply compartmentalized to the granulosa cells, and was expressed approximately equally in the ERKO animals and the WT controls. In contrast, ER alpha staining was present in the thecal cells but not the granulosa cells of the WT animals. The summary findings indicate that in the adult the major cause of the ERKO phenotype is high circulating LH interacting with functional LHR of the theca and granulosa cells. These features result in a failure of the normal maturational events leading to successful ovulation and luteinization and presumably involve both hypothalamic-pituitary and intraovarian mechanisms dependent upon ER alpha action. The presence of ER beta in the granulosa cells did not rescue the phenotype of the ovary.

Duke Scholars

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

June 1999

Volume

140

Issue

6

Start / End Page

2733 / 2744

Location

United States

Related Subject Headings

  • Receptors, LH
  • Receptors, FSH
  • Receptors, Estrogen
  • Rabbits
  • RNA, Messenger
  • Phenotype
  • Ovary
  • Ovarian Follicle
  • Mice, Knockout
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
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Schomberg, D. W., Couse, J. F., Mukherjee, A., Lubahn, D. B., Sar, M., Mayo, K. E., & Korach, K. S. (1999). Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult. Endocrinology, 140(6), 2733–2744. https://doi.org/10.1210/endo.140.6.6823
Schomberg, D. W., J. F. Couse, A. Mukherjee, D. B. Lubahn, M. Sar, K. E. Mayo, and K. S. Korach. “Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult.Endocrinology 140, no. 6 (June 1999): 2733–44. https://doi.org/10.1210/endo.140.6.6823.
Schomberg DW, Couse JF, Mukherjee A, Lubahn DB, Sar M, Mayo KE, et al. Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult. Endocrinology. 1999 Jun;140(6):2733–44.
Schomberg, D. W., et al. “Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult.Endocrinology, vol. 140, no. 6, June 1999, pp. 2733–44. Pubmed, doi:10.1210/endo.140.6.6823.
Schomberg DW, Couse JF, Mukherjee A, Lubahn DB, Sar M, Mayo KE, Korach KS. Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult. Endocrinology. 1999 Jun;140(6):2733–2744.
Journal cover image

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

June 1999

Volume

140

Issue

6

Start / End Page

2733 / 2744

Location

United States

Related Subject Headings

  • Receptors, LH
  • Receptors, FSH
  • Receptors, Estrogen
  • Rabbits
  • RNA, Messenger
  • Phenotype
  • Ovary
  • Ovarian Follicle
  • Mice, Knockout
  • Mice