Effect of ovarian hormones on intestinal mast cell reactivity to Substance P
Abstract
Evidence exists to support the concept that ovarian hormones influence mast cell functioning and related events. Here, we evaluated the constitutive gender difference and the influence of ovarian status on rat mast cell (MC) distribution in jejunum and colon, histamine synthesis and/or its release elicited by Substance P (SP). Higher mast cell (MC) number and histamine release were found in female compared with male. In female rats, hormonal status did not affect the density of resident MC neither in the jejunum nor in the colon. Interestingly, histamine levels released after SP stimulation of jejunal segment was reduced in ovariectomized (OVX) compared with sham OVX rats, and restored in OVX female receiving progesterone. In the colon, OVX resulted in a significant increase in histamine levels released after SP stimulation and a treatment with progesterone did not restore basal histamine levels. Thus, ovarian steroid hormones do not affect jejunal and colonic mast cell number. However, the hormonal status differently influences jejunal and colonic MC sensitivity to SP.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cited by
Sorted by citations
Barbara, G., Stanghellini, V., De Giorgio, R., Cremon, C., Cottrell, G. S., Santini, D., Pasquinelli, G., Morselli-Labate, A. M., Grady, E. F., Bunnett, N. W., et al. (2004) · Gastroenterology · doi:10.1053/j.gastro.2003.11.055 · Cited by 1,475 · see citing works
Advances in mast cell biology: new understanding of heterogeneity and function
Moon, T. C., Laurent, C. D. S., Morris, K., Marcet, C. T., Yoshimura, T., Sekar, Y., & Befus, A. D. (2009) · Mucosal Immunology · doi:10.1038/mi.2009.136 · Cited by 274 · see citing works
Piche, T., Saint-Paul, M. C., Dainese, R., Marine-Barjoan, E., Iannelli, A., Montoya, M. L., Peyron, J. F., Czerucka, D., Cherikh, F., Filippi, J., et al. (2008) · Gut · doi:10.1136/gut.2007.127068 · Cited by 198 · see citing works
PARK, J. H., RHEE, P., KIM, H. S., LEE, J. H., KIM, Y., KIM, J. J., & RHEE, J. C. (2006) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2005.04143.x · Cited by 196 · see citing works
Menopause Related Sleep Disorders
Eichling, P. S., & Sahni, J. (2005) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.26347 · Cited by 180 · see citing works
Janes, K., Wahlman, C., Little, J. W., Doyle, T. M., Tosh, D. K., Jacobson, K. A., & Salvemini, D. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.08.010 · Cited by 134 · see citing works
Age, Gender, and Women’s Health and the Patient
Houghton, L. A., Heitkemper, M. M., Crowell, M. D., Emmanuel, A. V., Halpert, A. D., McRoberts, J. A., & Toner, B. B. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.02.017 · Cited by 120 · see citing works
Visceral perception: inflammatory and non-inflammatory mediators
Bueno, L. P., & Fioramonti, J. (2002) · Gut · doi:10.1136/gut.51.suppl_1.i19 · Cited by 118 · see citing works
“The finding that this effect is blocked by doxantrazole, a mast cell stabiliser, suggests that mast cell degranulation is involved in the mechanism. Stress is thought to increase the synthesis of mast cell products such as histamine”
BackgroundSelf-citationWinnard, K. P., Dmitrieva, N., & Berkley, K. J. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00455.2006 · Cited by 111 · see citing works
Hesketh, P. J., Grunberg, S. M., Herrstedt, J., de Wit, R., Gralla, R. J., Carides, A. D., Taylor, A., Evans, J. K., & Horgan, K. J. (2006) · Supportive Care in Cancer · doi:10.1007/s00520-005-0914-4 · Cited by 98 · see citing works
“In other animal and human studies, gender differences in response to substance P were manifested in various ways, including differences in intestinal mast cell reactivity [3], regulation of NK1-receptor-mediated responses in vagal afferent neurons [15], stress-induced visceral hypersensitivity [4], and analgesic respo…”
BackgroundIdentification of A3adenosine receptor agonists as novel non‐narcotic analgesics
Janes, K., Symons-Liguori, A. M., Jacobson, K. A., & Salvemini, D. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13446 · Cited by 59 · see citing works
“These glial-derived proinflammatory mediators act not only on neurons but also on glial cells leading to an amplification loop that is potentially responsible for the long-lasting hypersensitivity underpinning some chronic pain states (Bradesi et al., 2001).”
BackgroundGuhl, S., Lee, H., Babina, M., Henz, B. M., & Zuberbier, T. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.02.015 · Cited by 58 · see citing works
Ouyang, A., & Wrzos, H. F. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00975.x · Cited by 57 · see citing works
“In light of the reported predisposing risk factor of infection and the report of a greater number of mucosal mast cells in the colon of subjects with IBS, it is of interest that there are more constitutive mast cell populations in the jejunum and colon in female rats compared with male rats (52, 53).”
BackgroundMuñoz-Cruz, S., Mendoza-Rodríguez, Y., Nava-Castro, K. E., Yepez-Mulia, L., & Morales-Montor, J. (2015) · Journal of Immunology Research · doi:10.1155/2015/351829 · Cited by 54 · see citing works
“Also, gender differences inMC reactivity and histamine content have been reported [28], indicating that sex steroids influence MC development and functionality; however, the exact mechanisms remain to be elucidated.”
BackgroundSethi, A., Jain, D., Roland, B. C., Kinzel, J., Gibson, J. A., Schrader, R., & Hanson, J. A. (2015) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2013-0594-oa · Cited by 52 · see citing works
Have We Just Scratched the Surface? A Narrative Review of Uremic Pruritus in 2020
Martin, C. E., Clotet‐Freixas, S., Farragher, J. F., & Hundemer, G. L. (2020) · Canadian Journal of Kidney Health and Disease · doi:10.1177/2054358120954024 · Cited by 50 · see citing works
Review article: microscopic colitis - lymphocytic, collagenous and ‘mast cell’ colitis
Yen, E. F., & Pardi, D. S. (2011) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2011.04686.x · Cited by 46 · see citing works
“models, increased mast cells have been described in females compared to males.(125) In addition, while a sig-”
BackgroundMullin, G. E., Shepherd, S. J., Roland, B. C., Ireton-Jones, C. S., & Matarese, L. E. (2014) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607114545329 · Cited by 44 · see citing works
Anti-superoxide and anti-peroxynitrite strategies in pain suppression
Janes, K., Neumann, W. L., & Salvemini, D. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.12.008 · Cited by 40 · see citing works
“These glial-derived proinflammatory mediators act not only on neurons, but also on glial cells leading to an amplification loop [71].”
BackgroundMast cells modulate maintained neuronal activity in the thalamus in vivo
Kovács, P., Hernádi, I., & Wilhelm, M. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.07.026 · Cited by 35 · see citing works
“Gender specific reactions may be related to the higher number, and the differently stored and ejected bioactive compounds of mast cells in the female thalamus, especially to those of serotonin and histamine (Asarian et al., 2002; Atkins et al., 1993; Bradesi et al., 2001; Crivellato et al., 1997; Csaba et al., 2003; G…”
BackgroundZia, J. K., & Heitkemper, M. M. (2016) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2016.02.003 · Cited by 35 · see citing works
Katsinelos, P., Lazaraki, G., Kountouras, J., Paroutoglou, G., Oikonomidou, I., Mimidis, K., Koutras, C., Gelas, G., Τζιόμαλος, Κ., Zavos, C., et al. (2009) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e328312eb97 · Cited by 33 · see citing works
Lee, J. Y., Kim, N., Kim, Y. S., Nam, R. H., Ham, M. H., Lee, H. S., Jo, W., Shim, Y. K., Choi, Y. J., Yoon, H., et al. (2016) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm16007 · Cited by 27 · see citing works
“Mast cell number and the amount of histamine secretion were higher in female rats than in the male rats.(34) In addition, in human studies, Sohn et al(35) showed that women with IBS had more mast cells than healthy women volunteers, and this trend was more predominant in women than in men.”
ResultSex Differences in Mast Cell–Associated Disorders: A Life Span PerspectivePreprint
Mackey, E. E., & Moeser, A. J. (2022) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a039172 · Cited by 17 · see citing works
Regular exercise modulates cardiac mast cell activation in ovariectomized rats
Phungphong, S., Kijtawornrat, A., Wattanapermpool, J., & Bupha‐Intr, T. (2015) · The Journal of Physiological Sciences · doi:10.1007/s12576-015-0409-0 · Cited by 15 · see citing works
Sex Differences in Gastrointestinal Physiology and Diseases
Houdeau, É. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802388-4.00008-2 · Cited by 15 · see citing works
Menopause and gastrointestinal health and disease
Ley, D., & Saha, S. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01075-7 · Cited by 13 · see citing works
“Oestrogen and progesterone receptors are found throughout the gastrointestinal tract, where they modulate nitric oxide-containing neurons in the myenteric plexus and influence the number and function of mast cells within the gastrointestinal mucosa 32,33 .”
Elliott, J., Wagner, A. F., & Lysle, D. T. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.08.011 · Cited by 10 · see citing works
Lucan, L. (2013) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2013.11 · Cited by 3 · see citing works
The Adenosine-Receptor Axis in Chronic Pain
Salvemini, D., Doyle, T. M., Largent‐Milnes, T. M., & Vanderah, T. W. (2018) · Springer eBooks · doi:10.1007/978-3-319-90808-3_16 · Cited by 1 · see citing works
Contribution of Gender to Pathophysiology and Clinical Presentation of IBS
Ouyang, A., & Wrzos, H. F. (2006) · The American Journal of Gastroenterology · doi:10.14309/00000434-200612001-00002 · Cited by 1 · see citing works
Barbara, G., & GIORGIO, R. D. (2004) · doi:10.1002/9780470760307.ch6 · Cited by 1 · see citing works
Lee, L., & Mullin, G. E. (2007) · CRC Press eBooks · doi:10.1201/9781420043013.ch13
IL-33 induces stronger responses in female mast cells and neutrophils: a role for the JNK pathway
Kee, S. A., Maldonado, T. D., Ching, J. M., Nelson, C., Hussain, Z. Y., Yao, A. Z., Kotha, A., Hamze, H., Burchett, J. R., & Ryan, J. J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1813530
“Kuhn et al. showed that ovary removal had no effect on peripheral neutrophils (67).”
- Authors
- Bradesi, S., Eutamene, H., Theodorou, V., Fioramonti, J., & Bueno, L.
- Affiliations
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Institut National de la Recherche Agronomique (FR)
- Corresponding author
- Bueno, L.
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 68
- Issue
- 9
- Pages
- 1047-1056
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2056790276
- Cited by
- 34
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2020: 1 · 2018: 1 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 1
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ovarian hormones, mast cells, substance P, histamine release, histamine synthesis, ovariectomy, progesterone, sex differences, jejunum, colon
- MeSH terms
- Animals, Cell Count, Colon, Female, Histamine, Histamine Release, Intestinal Mucosa, Jejunum, Male, Mast Cells, Ovariectomy, Ovary, Progesterone, Sex Characteristics, Gonadal Steroid Hormones, Substance P, Rats, Wistar, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
