Human chorionic gonadotropin-dependent regulation of 17beta-hydroxysteroid dehydrogenase type 4 in preovulatory follicles and its potential role in follicular luteinization.
Abstract: 17Beta-hydroxysteroid dehydrogenase type 4 (17betaHSD4) has a unique multidomain structure, with one domain involved in 17beta-estradiol inactivation. The objective of the study was to investigate the regulation of 17betaHSD4 during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine 17betaHSD4 cDNA was cloned and was shown to encode a 735-amino acid protein that is highly conserved (81-87% identity) compared with other mammalian orthologs. RT-PCR/Southern blot analyses were performed to study the regulation of 17betaHSD4 transcripts in equine preovulatory follicles isolated between 0-39 h after hCG treatment. Results showed the presence of basal 17betaHSD4 mRNA expression before hCG treatment, but an increase was observed in follicles obtained 24 h after hCG (P < 0.05). Analyses of isolated preparations of granulosa and theca interna cells identified basal mRNA expression in both layers, but granulosa cells appeared as the predominant site of follicular 17betaHSD4 mRNA induction. A specific polyclonal antibody was raised against a fragment of the equine protein and used to study regulation of the 17betaHSD4 protein. Immunoblots showed an increase in full-length 17betaHSD4 protein in follicles 24 h after hCG (P < 0.05), in keeping with mRNA results. Immunohistochemical data confirmed the induction of the enzyme in follicular cells after hCG treatment. Collectively, these results demonstrate that the gonadotropin-dependent induction of follicular luteinization is accompanied by an increase in 17betaHSD4 expression. Considering the estrogen-inactivating function of 17betaHSD4, its regulated expression in luteinizing preovulatory follicles appears as a potential complementary mechanism to reduce circulating levels of 17beta-estradiol after the LH surge.
Publication Date: 2004-01-15 PubMed ID: 14726434DOI: 10.1210/en.2003-1715Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research provides evidence that the expression of the enzyme 17Beta-hydroxysteroid dehydrogenase type 4 (17betaHSD4) is regulated in preovulatory follicles during ovulation caused by human chorionic gonadotropin (hCG). This enhanced expression could potentially play a role in reducing circulating levels of the hormone 17beta-estradiol after the LH (luteinizing hormone) surge in follicular luteinization.
Study Objective and Methodology
- The main aim of this investigation was to understand how 17betaHSD4 is regulated during hCG-induced ovulation or luteinization. Luteinization is a process that transforms the follicles in the ovary into a structure called the corpus luteum.
- To conduct this study, the researchers cloned the cDNA of equine 17betaHSD4, a protein that contains 735 amino acids and demonstrates high levels of similarity (81-87%) to other mammalian orthologs.
Findings
- Upon using RT-PCR and Southern blot analyses, the research showed that mRNA expression of 17betaHSD4 was present before the hCG treatment. However, there was a significant increase in follicles extracted 24 hours post hCG treatment.
- The researchers were also able to isolate granulosa and theca interna cells and found out that mRNA was present in both layers, but it was primarily expressed in the granulosa cells.
- A polyclonal antibody was also produced against a fragment of the equine protein to study the regulation of the 17betaHSD4 protein. Immunoblots, as well as immunohistochemical data, confirmed an increase in the full-length 17betaHSD4 protein post 24 hours of hCG treatment, supporting the mRNA findings.
Conclusion
- From this research, it could be inferred that the hCG-induced initiation of follicular luteinization is accompanied by a significant increase in the expression of 17betaHSD4.
- Given that 17betaHSD4 deactivates the hormone 17beta-estradiol, the enhanced presence of this enzyme in luteinizing preovulatory follicles could potentially offer an additional mechanism for reducing the circulating levels of 17beta-estradiol post the LH surge, contributing further to the process of luteinization.
Cite This Article
APA
Brown KA, Boerboom D, Bouchard N, Doré M, Lussier JG, Sirois J.
(2004).
Human chorionic gonadotropin-dependent regulation of 17beta-hydroxysteroid dehydrogenase type 4 in preovulatory follicles and its potential role in follicular luteinization.
Endocrinology, 145(4), 1906-1915.
https://doi.org/10.1210/en.2003-1715 Publication
Researcher Affiliations
- Centre de Recherche en Reproduction Animale, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada J2S 7C6.
MeSH Terms
- 17-Hydroxysteroid Dehydrogenases / genetics
- 17-Hydroxysteroid Dehydrogenases / metabolism
- Amino Acid Sequence
- Animals
- Base Sequence
- Chorionic Gonadotropin / pharmacology
- DNA, Complementary / genetics
- Female
- Follicular Phase / metabolism
- Horses
- Isoenzymes / genetics
- Isoenzymes / metabolism
- Luteinization / physiology
- Molecular Sequence Data
- Ovarian Follicle / enzymology
- RNA, Messenger / metabolism
- Tissue Distribution
Citations
This article has been cited 1 times.- Richards RC, Short CE, Driedzic WR, Ewart KV. Seasonal changes in hepatic gene expression reveal modulation of multiple processes in rainbow smelt (Osmerus mordax).. Mar Biotechnol (NY) 2010 Nov;12(6):650-63.
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