Abstract
BackgroundIn several species, considerably higher levels of estradiol-17 (E2) are synthesized in the CL. E2 has been suggested to participate in the regulation of luteal steroidogenesis and luteal cell morphology. In pregnant rats, several experiments have been carried out to examine the effects of inhibition of luteal E2 synthesis on CL structure and function.MethodsDuring days 12–15 of pregnancy in rats, luteal E2 was inhibited by way of daily oral administration of anastrozole (AI), a selective non-steroidal aromatase inhibitor, and experiments were also performed with E2 replacement i.e. AI+ E2 treatments. Luteal tissues from different treatment groups were subjected to microarray analysis and the differentially expressed genes in E2 treated group were further examined for expression of specific E2 responsive genes. Additional experiments were carried out employing recombinant growth hormone preparation and flutamide, an androgen receptor antagonist, to further address the specificity of E2 effects on the luteal tissue.ResultsMicroarray analysis of CL collected on day 16 of pregnancy post AI and AI+E2 treatments showed significantly lowered cyp19a1 expression, E2 levels and differential expression of a number of genes, and several of them were reversed in E2 replacement studies. From the differentially expressed genes, a number of E2 responsive genes were identified. In CL of AI pregnant rats, non-significant increase in expression of igf1, significant increase in igbp5, igf1r and decrease in expression of Erα were observed. In liver of AI treated rats, igf1 expression did not increase, but GH treatment significantly increased expression that was further increased with AI treatment. In CL of GH and AI+GH treated rats, expression of igfbp5 was higher. Administration of flutamide during days 12–15 of pregnancy resulted in non-significant increase in igfbp5 expression, however, combination of flutamide+AI treatments caused increased protein expression. Expression of few of the molecules in PI3K/Akt kinase pathway in different treatments was determined.ConclusionsThe results suggest a role for E2 in the regulation of luteal steroidogenesis, morphology and proliferation. igfbp5 was identified as one the E2 responsive genes with important role in the mediation of E2 actions such as E2-induced phosphorylation of PI3K/Akt kinase pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-016-0153-1) contains supplementary material, which is available to authorized users.
Highlights
In several species, considerably higher levels of estradiol-17 (E2) are synthesized in the corpus luteum (CL)
The rat CL is unique in that expression of Cyp19a1is highest, and it has been reported that androgens synthesized in placenta are transported to CL for aromatization into E2, since placenta lacks Cyp19a1expression [19, 40]
Inhibition of E2 was accomplished by administration of specific aromatase inhibitor (AI)..In this study microarray analysis was performed to examine differential expression of E2 responsive genes with a view to address critical issue of specific effect/action of E2 on CL function
Summary
Considerably higher levels of estradiol-17 (E2) are synthesized in the CL. Several experiments have been carried out to examine the effects of inhibition of luteal E2 synthesis on CL structure and function. In a recent study from our laboratory, differential expression of many E2 responsive genes in the luteal tissue was observed during induced luteolysis in two distinct animal models, macaque and the bovine species [32]. A number of experiments were carried out to test the hypothesis that E2 plays a critical role in the maintenance of luteal function in rats. Inhibition of E2 was accomplished by administration of specific aromatase inhibitor (AI)..In this study microarray analysis was performed to examine differential expression of E2 responsive genes with a view to address critical issue of specific effect/action of E2 on CL function. The results suggest novel roles for IGFBP5 during proliferation and hypertrophy of luteal cells in the control of luteal function
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