Gender, sex hormones, and vascular tone
Abstract
The greater incidence of hypertension and coronary artery disease in men and postmenopausal women compared with premenopausal women has been related, in part, to gender differences in vascular tone and possible vascular protective effects of the female sex hormones estrogen and progesterone. However, vascular effects of the male sex hormone testosterone have also been suggested. Estrogen, progesterone, and testosterone receptors have been identified in blood vessels of human and other mammals and have been localized in the plasmalemma, cytosol, and nuclear compartments of various vascular cells, including the endothelium and the smooth muscle. The interaction of sex hormones with cytosolic/nuclear receptors triggers long-term genomic effects that could stimulate endothelial cell growth while inhibiting smooth muscle proliferation. Activation of plasmalemmal sex hormone receptors may trigger acute nongenomic responses that could stimulate endothelium-dependent mechanisms of vascular relaxation such as the nitric oxide-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Additional endothelium-independent effects of sex hormones may involve inhibition of the signaling mechanisms of vascular smooth muscle contraction such as intracellular Ca 2+ concentration and protein kinase C. The sex hormone-induced stimulation of the endothelium-dependent mechanisms of vascular relaxation and inhibition of the mechanisms of vascular smooth muscle contraction may contribute to the gender differences in vascular tone and may represent potential beneficial vascular effects of hormone replacement therapy during natural and surgically induced deficiencies of gonadal hormones.
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Estrogen and progesterone receptors occur in nonreproductive tissues that regulate fluid, including the hypothalamus, cardiovascular system, and kidney tubules.
“Receptors for estrogens and progesterone are found in nonreproductive tissue involved in fluid regulation, such as the hypothalamus (10,21), the cardiovascular system (6,19), and the kidney tubules (6).”
From Sex Hormone Effects on Body Fluid Regulation (2008) · cites this paper as [19]
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- Authors
- Orshal, J. M., & Khalil, R. A.
- Affiliations
- Harvard University (US)
- ORCID
- Khalil, Raouf A.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2004-02
- Volume
- 286
- Issue
- 2
- Pages
- R233-R249
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2038482691
- Cited by
- 650
- References
- 0
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 23 · 2023: 25 · 2022: 20 · 2021: 28 · 2020: 20 · 2019: 27 · 2018: 20 · 2017: 21 · 2016: 29 · 2015: 33 · 2014: 27 · 2013: 36 · 2012: 39
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r29hl052696-06)
- National Heart, Lung, and Blood Institute (HL-52696, R01HL070659, HL-70659, HL 65998, R01HL065998)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- sex hormones, vascular tone, estrogen, progesterone, testosterone, sex hormone receptors, gender differences, hypertension, coronary artery disease, postmenopausal women, endothelium-dependent relaxation, vascular smooth muscle contraction, nitric oxide-cGMP pathway, hyperpolarization, intracellular calcium, protein kinase C, hormone replacement therapy
- MeSH terms
- Animals, Humans, Sex Characteristics, Gonadal Steroid Hormones, Vasomotor System
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