Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/60690
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Type: Journal article
Title: Hormonally regulated follicle differentiation and luteinization in the mouse is associated with hypoxia inducible factor activity
Author: Tam, K.
Russell, D.
Peet, D.
Bracken, C.
Rodgers, R.
Thompson, J.
Kind, K.
Citation: Molecular and Cellular Endocrinology, 2010; 327(1-2):47-55
Publisher: Elsevier Sci Ireland Ltd
Issue Date: 2010
ISSN: 0303-7207
1872-8057
Statement of
Responsibility: 
Kimberley K.Y. Tam, Darryl L. Russell, Daniel J. Peet, Cameron P. Bracken, Raymond J. Rodgers, Jeremy G. Thompson, and Karen L. Kind
Abstract: Hypoxia inducible factors (HIFs) are transcription factors that mediate physiological responses to hypoxia. Hypoxia is established as the major inducer of HIFs, but stimuli such as transition metals and hormones also induce HIF target genes. Whilst the ovarian granulosa cell layer is known to be avascular and the follicle is vascularised via the thecal cell layer, little is known about the role of hypoxia or HIFs in regulating ovarian function. In this study, we hypothesized that hypoxia as well as non-hypoxic stimuli cooperate in promoting follicle differentiation and luteinization via HIF activity and resultant gene regulation. We quantitatively measured the HIF1alpha protein response to hCG in ovarian granulosa cell cultures and in vivo and developed a transgenic (HRE(4)-SV40-EGFP) HIF reporter mouse line. We observed a time-dependent increase of HIF1alpha protein levels in granulosa cells post-hCG in vivo, maximal around time of ovulation. hCG alone was unable to promote HIF1alpha protein accumulation in cultured granulosa cells, but increased protein abundance was observed when combined with a hypoxic stimulus. HRE-EGFP ovaries showed no follicular EGFP in stages prior to antrum formation. However, HIF regulated EGFP was maximally induced in granulosa cells around the time of ovulation and readily observed in corpora lutea. There was also an increase in HIF regulated EGFP activity in the corpora lutea from functional to regressing stages. Taken together, these observations establish the notion that HIFs play a role during follicular differentiation and luteinization.
Keywords: Follicle; Ovulation; Human chorionic gonadotropin; Hypoxia inducible factor
Rights: Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
RMID: 0020100519
DOI: 10.1016/j.mce.2010.06.008
Grant ID: http://purl.org/au-research/grants/nhmrc/453556
Appears in Collections:Molecular and Biomedical Science publications

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