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Overexpression of androgen-binding protein/sex hormone-binding globulin in male transgenic mice: tissue distribution and phenotypic disorders.

Publication ,  Journal Article
Joseph, DR; O'Brien, DA; Sullivan, PM; Becchis, M; Tsuruta, JK; Petrusz, P
Published in: Biol Reprod
January 1997

The rat androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) gene in transgenic mice was previously shown to be specifically expressed in the testes. This study verifies a Sertoli cell location of ABP and translation of testicular ABP mRNA in the transgenic mice by dihydrotestosterone (DHT)-binding assays and immunohistochemistry. DHT-binding activities in the testis and epididymis of the hemizygous transgenic mice were elevated 20-fold as compared to activity in the wild-type tissues. DHT-binding activities were also elevated in blood plasma at least 25- to 50-fold in the transgenic mice; binding was undetectable in the plasma from control mice. Immunohistochemical analysis revealed that the transgenic testicular ABP was primarily in the cytoplasm of Sertoli cells and lumen of the seminiferous tubules. In some tubules, intense staining also was associated with spermatids. After transport to the epididymis, there were large amounts of immunoreactive ABP internalized in the epithelium of the initial segment and proximal caput. The increased levels of plasma and testicular ABP had no effect on levels of testosterone; there was a 30-fold range of plasma and testicular testosterone levels in the wild-type and transgenic mice. Increased ABP levels in the transgenic mice were associated with structural and functional abnormalities in the testis. Abnormal spermatogenesis resulted in extensive structural changes in the transgenic testis; the degree of the defect varied from near normality to the loss of most germ cells. In the affected mice, seminiferous tubules had smaller diameters and decreased numbers of germ cells, particularly in the spermatid stages of differentiation. Pyknotic nuclei and multinucleated cells were associated with the spermatids in the defective tubules, but not in the wild-type tubules. Consequently, mice with the spermatogenic disorder had reduced epididymal sperm numbers. The variable spermatogenic disorder was associated with variable male fertility. The homozygous transgenic male and female mice also had a serious motor dysfunction affecting their hind limbs. This study demonstrates how the transgenic mouse model can be used to study ABP's function, and the data support several hypotheses on its function in the testis and epididymis.

Duke Scholars

Published In

Biol Reprod

DOI

ISSN

0006-3363

Publication Date

January 1997

Volume

56

Issue

1

Start / End Page

21 / 32

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Testosterone
  • Testis
  • Spermatogenesis
  • Sex Hormone-Binding Globulin
  • Sertoli Cells
  • Rats
  • RNA, Messenger
  • Proteins
  • Phenotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Joseph, D. R., O’Brien, D. A., Sullivan, P. M., Becchis, M., Tsuruta, J. K., & Petrusz, P. (1997). Overexpression of androgen-binding protein/sex hormone-binding globulin in male transgenic mice: tissue distribution and phenotypic disorders. Biol Reprod, 56(1), 21–32. https://doi.org/10.1095/biolreprod56.1.21
Joseph, D. R., D. A. O’Brien, P. M. Sullivan, M. Becchis, J. K. Tsuruta, and P. Petrusz. “Overexpression of androgen-binding protein/sex hormone-binding globulin in male transgenic mice: tissue distribution and phenotypic disorders.Biol Reprod 56, no. 1 (January 1997): 21–32. https://doi.org/10.1095/biolreprod56.1.21.
Joseph DR, O’Brien DA, Sullivan PM, Becchis M, Tsuruta JK, Petrusz P. Overexpression of androgen-binding protein/sex hormone-binding globulin in male transgenic mice: tissue distribution and phenotypic disorders. Biol Reprod. 1997 Jan;56(1):21–32.
Joseph, D. R., et al. “Overexpression of androgen-binding protein/sex hormone-binding globulin in male transgenic mice: tissue distribution and phenotypic disorders.Biol Reprod, vol. 56, no. 1, Jan. 1997, pp. 21–32. Pubmed, doi:10.1095/biolreprod56.1.21.
Joseph DR, O’Brien DA, Sullivan PM, Becchis M, Tsuruta JK, Petrusz P. Overexpression of androgen-binding protein/sex hormone-binding globulin in male transgenic mice: tissue distribution and phenotypic disorders. Biol Reprod. 1997 Jan;56(1):21–32.

Published In

Biol Reprod

DOI

ISSN

0006-3363

Publication Date

January 1997

Volume

56

Issue

1

Start / End Page

21 / 32

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Testosterone
  • Testis
  • Spermatogenesis
  • Sex Hormone-Binding Globulin
  • Sertoli Cells
  • Rats
  • RNA, Messenger
  • Proteins
  • Phenotype