NYMC Faculty Publications

Journal Title

International Journal of Endocrinology

First Page

Art. ID.: 3473105

Document Type

Article

Publication Date

7-1-2018

Department

Cell Biology and Anatomy

Abstract

The "estrogen paradox" in pulmonary arterial hypertension (PAH) refers to observations that while there is a higher incidence of idiopathic PAH in women, rodent models of PAH show male dominance and estrogens are protective. To explain these differences, we previously proposed the neuroendocrine-STAT5-BCL6 hypothesis anchored in the sex-biased and species-specific patterns of growth hormone (GH) secretion by the pituitary, the targeting of the hypothalamus by estrogens to feminize GH secretion patterns, and the role of the transcription factors STAT5a/b and BCL6 as downstream mediators of this patterned GH-driven sex bias. As a test of this hypothesis, we previously reported that vascular smooth muscle cell- (SMC-) specific deletion of the STAT5a/b locus abrogated the male-dominant sex bias in the chronic hypoxia model of PAH in mice. In the present study, we confirmed reduced BCL6 expression in pulmonary arterial (PA) segments in both male and female SMC:STAT5a/b-/- mice. In order to test the proposed contribution of BCL6 to sex bias in PAH, we developed mice with SMC-specific deletion of BCL6+/- by crossing SM22alpha-Cre mice with BCL6-floxed mice and investigated sex bias in these mutant mice in the chronic hypoxia model of PAH. We observed that the male-bias observed in wild-type- (wt-) SM22alpha-Cre-positive mice was abrogated in the SMC:BCL6+/- knockouts-both males and females showed equivalent enhancement of indices of PAH. The new data confirm BCL6 as a contributor to the sex-bias phenotype observed in hypoxic PAH in mice and support the neuroendocrine-STAT5-BCL6 hypothesis of sex bias in this experimental model of vascular disease.

Publisher's Statement

Originally published in International Journal of Endocrinology, 2018, Article ID 3473105. The original material can be found here.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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