Human Sex Hormone-Binding Globulin Gene Expression in Transgenic Mice
Abstract
The sex hormone-binding globulin gene (shbg) is expressed in the liver and testis as well as in several other tissues that play important roles in reproduction. Expression of shbg in the human liver results in the production of plasma sex hormone-binding globulin (SHBG), which regulates the bioavailability of sex steroids in the blood. Although shbg is not expressed in rodent livers postnatally, it gives rise to the androgen-binding protein in their testes upon sexual maturation. Human shbg is also expressed in the testis, but its products and their function are less well characterized. To study the expression of human shbg in different tissues and the consequences of overexpressing this gene in vivo, we have produced several lines of mice containing approximately 11-kilobase (kb; shbg11) or 4.3-kb (shbg4) human shbg genomic fragments that comprise all eight exons encoding SHBG as well as approximately 6 kb or approximately 0.9 kb of 5'-flanking DNA, respectively. Northern blots indicated that human shbg transcripts were most abundant in liver, kidney, and testis of the shbg11 mice. The 4.3-kb shbg transgenes were expressed at similar levels in liver and kidney, but the abundance of human shbg transcripts in their testes was much lower than that in shbg11 mice. Primer extension analysis indicated that transcription starts 60 bp from the translation initiation codon for SHBG in liver and kidney of shbg11 mice, and that the shbg transcripts in their testis are derived from a se…
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A mouse model with a gene addition of the 4.3 kb human SHBG uncovered that upstream of exon 1, a sequence of approximately 0.9 kb suffices for high gene expression levels.
“A mouse model with a gene addition of the 4.3 kb human SHBG uncovered that upstream of exon 1, a sequence of approximately 0.9 kb suffices for high gene expression levels [47].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [47]
Transgenic animal models expressing human SHBG had higher concentrations of testosterone compared to wildtype mice.
“These transgenic animal models expressing human SHBG had higher concentrations of T compared to wildtype mice [47].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [47]
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- Authors
- Jänne, M., Deol, H. K., Power, S. G. A., Yee, S.-P., & Hammond, G. L.
- Affiliations
- Western University (CA)
- Corresponding author
- Hammond, Geoffrey L.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1998-01
- Volume
- 12
- Issue
- 1
- Pages
- 123-136
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2077871909
- Cited by
- 113
- References
- 0
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 8 · 2016: 4 · 2015: 6 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- sex hormone-binding globulin, transgenic mice, androgen-binding protein, alternative promoters, Sertoli cells, spermatogenesis, liver, testis, kidney, hepatocytes, proximal convoluted tubule, tissue-specific gene expression, transcription start sites, transgenic overexpression
- MeSH terms
- Animals, Chromosome Mapping, Gene Expression Regulation, Humans, Male, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Organ Specificity, Phenotype, RNA, Messenger, Sex Hormone-Binding Globulin, Testosterone, Transcription, Genetic, Transgenes, Mice
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