Cellular localization of androgen synthesis in equine granulosa-theca cell tumors: immunohistochemical expression of 17alpha-hydroxylase/17,20-lyase cytochrome P450.
Abstract: Elevated blood testosterone concentrations, often accompanied by male-typical behaviors, is a common signalment of mares with granulosa-theca cell tumors (GCTCs), but no definitive information exists regarding the cellular differentiation of tumors associated with androgen secretion. This study was conducted to localize and thereby define the cellular expression of 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17), the enzyme most directly responsible for androgen synthesis, in 30 GTCTs and control tissues (gonads and adrenal glands) using immuno-histochemistry (IHC). Immuno-reactivity for P450c17 was evident in approximately half of 30 specimens examined, was most consistent in the interstitial cells surrounding existing or developing cysts, and was less intense in cells within cysts in the smaller proportion of specimens where this was observed. In control tissues, the expression of P450c17 was localized primarily in theca interna of normal ovarian follicles, in theca-lutein cells of some corpora lutea, but not in granulosa-lutein cells. Testicular interstitial cells and islands of adreno-cortical cells located in the adrenal medulla of the adrenal cortex further established the specificity of the antisera used. These data provided the first substantive evidence that polyhedral cells identified previously in GTCTs by histopathology have the potential to synthesize and secrete androgens, similar to theca interna and theca lutein cells in normal equine ovaries.
Copyright 2010 Elsevier Inc. All rights reserved.
Publication Date: 2010-04-22 PubMed ID: 20416939DOI: 10.1016/j.theriogenology.2010.02.022Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article is about a study that used immunohistochemistry to locate the cellular expression of an enzyme in granulosa-theca cell tumors (GTCTs) in horses. This enzyme is responsible for the synthesis of androgens in these tumors.
Background
- The study focuses on granulosa-theca cell tumors (GTCTs) often found in female horses. One of the common symptoms in these horses is an increase in blood testosterone levels, which usually leads to male-like behavior.
- Despite the symptoms, there was a lack of solid information about how the GTCTs and androgen secretion were linked. This investigation aimed to solve that gap by looking at the expression of a particular enzyme,17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17), known for its potent role in androgen production.
Methodology
- The researchers explored P450c17 expression in 30 GTCTs and control tissues from reproductive organs and adrenal glands, employing a method called immunohistochemistry (IHC). This technique involves staining specific proteins (in this case, P450c17) in a tissue section to observe precisely where the protein is produced.
Findings
- The investigation revealed the presence of P450c17 was significantly accessible in sample tissues. It was more consistently observed in the interstitial cells located around existing or forming cysts. Immuno-reactivity was less intense within the cysts themselves in the smaller proportion of specimens.
- In control tissues, P450c17 expression was found mostly in theca interna cells within normal ovarian follicles, in theca-lutein cells in some corpora lutea, but not in granulosa-lutein cells. The expression was also noticeable in testicular interstitial cells and clusters of adrenal cortical cells in the adrenal medulla, supporting the specificity of the applied antisera.
- The results presented the first strong evidence that some particular cells (polyhedral cells) previously identified in GTCTs by histopathology do indeed have the potential to generate and secrete androgens, much like theca interna and theca lutein cells in normal horse ovaries.
Implications
- This study’s results provide significant insights into why mares with GTCTs exhibit increased blood testosterone levels and male-typical behaviours. They also contribute crucial knowledge to the field of equine reproductive pathology and can be used in coming up with more effective diagnostic tools and treatments for GTCTs.
Cite This Article
APA
Neto AC, Ball BA, Browne P, Conley AJ.
(2010).
Cellular localization of androgen synthesis in equine granulosa-theca cell tumors: immunohistochemical expression of 17alpha-hydroxylase/17,20-lyase cytochrome P450.
Theriogenology, 74(3), 393-401.
https://doi.org/10.1016/j.theriogenology.2010.02.022 Publication
Researcher Affiliations
- Department of Population Health & Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
MeSH Terms
- Androgens / biosynthesis
- Animals
- Female
- Granulosa Cell Tumor / enzymology
- Granulosa Cell Tumor / metabolism
- Granulosa Cell Tumor / veterinary
- Horse Diseases / enzymology
- Horse Diseases / metabolism
- Horses
- Immunohistochemistry
- Male
- Ovarian Neoplasms / enzymology
- Ovarian Neoplasms / metabolism
- Ovarian Neoplasms / veterinary
- Steroid 17-alpha-Hydroxylase / metabolism
- Thecoma / enzymology
- Thecoma / metabolism
- Thecoma / veterinary
Citations
This article has been cited 4 times.- Dolin A, Schweiger P, Waselau M, Egerbacher M, Walter I. Immunohistochemical markers for equine granulosa cell tumors: a pilot study.. J Equine Sci 2023 Jun;34(2):37-46.
- Cui L, Bao H, Liu Z, Man X, Liu H, Hou Y, Luo Q, Wang S, Fu Q, Zhang H. hUMSCs regulate the differentiation of ovarian stromal cells via TGF-β(1)/Smad3 signaling pathway to inhibit ovarian fibrosis to repair ovarian function in POI rats.. Stem Cell Res Ther 2020 Sep 7;11(1):386.
- Lu X, Bao H, Cui L, Zhu W, Zhang L, Xu Z, Man X, Chu Y, Fu Q, Zhang H. hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway.. Stem Cell Res Ther 2020 Jul 3;11(1):268.
- Momeni M, Kalir T, Farag S, Chuang L, Fishman D, Burstein DE. Expression of H1.5 and PLZF in granulosa cell tumors and normal ovarian tissues: a short report.. Cell Oncol (Dordr) 2014 Jun;37(3):229-34.
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