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Critchley, H.O. et al.

Critchley, Osei, Henderson, Boswell, Sales, Jabbour, Hirani,

Hypoxia-inducible factor-1alpha expression in human endometrium and its regulation by prostaglandin E-series prostanoid receptor 2 ( EP2).

The menstrual cycle is a complex interaction of sex steroids, prostanoids, and cytokines that lead to coordinated tissue degradation, regeneration and repair. The transcription factor hypoxia-inducible factor (HIF-1) plays critical roles in cellular responses to hypoxia, the generation of an inflammatory response and vasculogenesis through transcriptional activation of angiogenic genes. We hypothesize that HIF-1 is expressed in human endometrium and that locally synthesized prostaglandins (PGE2 and PGF(2alpha)) regulate HIF-1 activity. Here we demonstrate that PGE2 up-regulates HIF-1alpha mRNA and protein via the E-series prostanoid receptor 2 ( EP2), and this up-regulation is dependent on epidermal growth factor receptor kinase activity. We show the tight temporal-spatial confinement of HIF-1alpha protein expression in endometrium across the cycle. HIF-1alpha is expressed exclusively during the secretory and menstrual phases. Protein expression is maximal at progesterone withdrawal during the late secretory and menstrual phase. HIF-1alpha protein colocalizes with prostaglandin EP2 receptor in glandular cells. In contrast, HIF-1beta/aryl receptor nuclear translocator 1 expression occurs throughout the cycle but is maximal in glandular cells during the proliferative phase. This provides evidence for a role for HIF-1 in the menstrual cycle and demonstrates that HIF-1 activation in human endometrium may occur via a PGE2-regulated pathway and provides a coordinated pathway from progesterone withdrawal through to angiogenic gene expression via HIF-1.[1]

References

Hypoxia-inducible factor-1alpha expression in human endometrium and its regulation by prostaglandin E-series prostanoid receptor 2 (EP2). Critchley, H.O., Osei, J., Henderson, T.A., Boswell, L., Sales, K.J., Jabbour, H.N., Hirani, N. Endocrinology (2006) [Pubmed]

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