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Cross-talk between gonadotropin-releasing hormones and progesterone receptor in neuroendocrine cells An, Beum-Soo
Abstract
Hypothalamic gonadotropin-releasing hormone (GnRH) is a decapeptide that plays a pivotal role in mammalian reproduction. It is hypothesized that progesterone (P4) may regulate GnRH I, GnRH II (a second form of GnRH) and GnRH I receptor (GnRH I R) at the transcriptional level. Alternatively, GnRHs may stimulate transactivation of the progesterone receptor (PR), thereby, modulating gonadotropin subunit gene expression. Treatment of human neuronal cells with P4 suppressed GnRH I R promoter activity. This P4-stimulated inhibition was enhanced when PR A was over-expressed. With respect to the two GnRHs, P4 increased GnRH I mRNA levels, but did not significantly affect GnRH II gene expression. Regulation of gonadotropin production involves interplay between steroids and neuropeptides, thus we have examined the effects of GnRHs on PR activation in pituitary cells. Treatment with GnRHs increased a progesterone response element (PRE)-luciferase reporter gene activity. PR was phosphorylated at Ser294 and translocated into nucleus after GnRH treatment in the absence of P4. Interactions between the PR and several coactivators were examined, and treatment with GnRHs specifically induced PR: Steroid Receptor Coactivator-3 (SRC-3) interaction. In chromatin immunoprecipitation assays, recruitment of PR and SRC-3 to the PRE reporter gene was also increased by GnRHs. The knockdown of GnRH I R and SRC-3 levels by siRNA treatment reduced GnRH-induced PR transactivation. Gonadotropin subunit gene expression was evaluated following treatment with GnRHs, and common α-subunit and FSHβ transcription were upregulated by GnRHs. We used siRNA for PR to examine the involvement of PR in GnRH I-induced FSHβ gene expression. The effect of GnRH I on FSHβ, but not α -subunit gene expression was reduced when siRNA targeting PR was introduced. In summary, these results indicate that P4 is a potent regulator of GnRH I R and GnRH I at the transcriptional level, and this distinct effect of P4 on the GnRH system may be derived from the differential action of PR A or PR B . Conversely, GnRHs can activate PR-mediated transcription in the absence of P4, and this ligand-independent mechanism of PR additionally regulates FSHβ subunit gene expression.
Item Metadata
Title |
Cross-talk between gonadotropin-releasing hormones and progesterone receptor in neuroendocrine cells
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2007
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Description |
Hypothalamic gonadotropin-releasing hormone (GnRH) is a decapeptide that plays a
pivotal role in mammalian reproduction. It is hypothesized that progesterone (P4) may regulate
GnRH I, GnRH II (a second form of GnRH) and GnRH I receptor (GnRH I R) at the
transcriptional level. Alternatively, GnRHs may stimulate transactivation of the progesterone
receptor (PR), thereby, modulating gonadotropin subunit gene expression. Treatment of human
neuronal cells with P4 suppressed GnRH I R promoter activity. This P4-stimulated inhibition
was enhanced when PR A was over-expressed. With respect to the two GnRHs, P4 increased
GnRH I mRNA levels, but did not significantly affect GnRH II gene expression.
Regulation of gonadotropin production involves interplay between steroids and neuropeptides,
thus we have examined the effects of GnRHs on PR activation in pituitary cells.
Treatment with GnRHs increased a progesterone response element (PRE)-luciferase reporter gene
activity. PR was phosphorylated at Ser294 and translocated into nucleus after GnRH treatment in
the absence of P4. Interactions between the PR and several coactivators were examined, and
treatment with GnRHs specifically induced PR: Steroid Receptor Coactivator-3 (SRC-3)
interaction. In chromatin immunoprecipitation assays, recruitment of PR and SRC-3 to the PRE
reporter gene was also increased by GnRHs. The knockdown of GnRH I R and SRC-3 levels by
siRNA treatment reduced GnRH-induced PR transactivation. Gonadotropin subunit gene
expression was evaluated following treatment with GnRHs, and common α-subunit and FSHβ
transcription were upregulated by GnRHs. We used siRNA for PR to examine the involvement of
PR in GnRH I-induced FSHβ gene expression. The effect of GnRH I on FSHβ, but not α -subunit
gene expression was reduced when siRNA targeting PR was introduced.
In summary, these results indicate that P4 is a potent regulator of GnRH I R and GnRH I at the transcriptional level, and this distinct effect of P4 on the GnRH system may be derived from the
differential action of PR A or PR B . Conversely, GnRHs can activate PR-mediated transcription in
the absence of P4, and this ligand-independent mechanism of PR additionally regulates FSHβ
subunit gene expression.
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Genre | |
Type | |
Language |
eng
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Date Available |
2011-01-20
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0100314
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.