Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2016 May 15;193(10):1087-90.
doi: 10.1164/rccm.201512-2541ED.

Estrogens in Men: Another Layer of Complexity of Estradiol Metabolism in Pulmonary Hypertension

Stevan P Tofovic  1 , Edwin K Jackson  2
Affiliations
Comment

Estrogens in Men: Another Layer of Complexity of Estradiol Metabolism in Pulmonary Hypertension

Stevan P Tofovic et al. Am J Respir Crit Care Med. .
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
(A) Metabolism of sex steroids: steroid sulfatase (STS) and sulfotransferase (SULT) control the delicate balance between inactive sulfated sex steroids and sex steroids and their biologically active metabolites and metabolic precursors. *Beneficial effects in experimental pulmonary arterial hypertension (PAH). #Adverse effects in experimental PAH. Yellow boxes: precursors of estrogen synthesis. Red, violet, and blue boxes: high, intermediate, and no estrogenic activity, respectively. (B) Inflammation and estradiol (E2) feed-forward mechanisms. In PAH, CYP1B1 may be a “hub” for instigating and perpetuating an estradiol feed-forward mechanism that involves estradiol metabolites and BMPR2, resulting in stimulation of angioproliferation (red arrows: increases enzyme expression/activity, estradiol and arachidonic acid metabolites production, estradiol levels and inflammation, and BMPR2 down-regulation). (C) Three-tier effects of estradiol in PAH. The effect on vascular pathobiology, progression, and prognosis of PAH is shown. BMPR2 = bone morphogenetic protein receptor type 2; COMT = catechol-O-methyltransferase; CYP = cytochrome p450 enzymes; DHEA-S = dehydroepiandrosterone sulfate; EETs = epoxyeicosatrienoic acids; HETEs = hydroxyeicosatetraenoic acids; HSD = hydroxysteroid dehydrogenase; RV = right ventricle.
See this image and copyright information in PMC

Comment on

References

    1. Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, Barst RJ, Benza RL, Liou TG, Turner M, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137:376–387. - PubMed
    1. Tofovic SP. Estrogens and development of pulmonary hypertension: interaction of estradiol metabolism and pulmonary vascular disease. J Cardiovasc Pharmacol. 2010;56:696–708. - PMC - PubMed
    1. Austin ED, Lahm T, West J, Tofovic SP, Johansen AK, Maclean MR, Alzoubi A, Oka M. Gender, sex hormones and pulmonary hypertension. Pulm Circ. 2013;3:294–314. - PMC - PubMed
    1. Ventetuolo CE, Baird GL, Barr RG, Bluemke DA, Fritz JS, Hill NS, Klinger JR, Lima JA, Ouyang P, Palevsky HI, et al. Higher estradiol and lower dehydroepiandrosterone-sulfate levels are associated with pulmonary arterial hypertension in men. Am J Respir Crit Care Med. 2016;193:1168–1175. - PMC - PubMed
    1. Roberts KE, Fallon MB, Krowka MJ, Brown RS, Trotter JF, Peter I, Tighiouart H, Knowles JA, Rabinowitz D, Benza RL, et al. Pulmonary Vascular Complications of Liver Disease Study Group. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. Am J Respir Crit Care Med. 2009;179:835–842. - PMC - PubMed

LinkOut - more resources