Bladder mast cell expression of high affinity oestrogen receptors in patients with interstitial cystitis.
OBJECTIVE
To investigate the role of oestrogens in the pathophysiology of interstitial cystitis (IC), specifically with respect to activated bladder mast cells (MC), as well as urine concentrations of MC-derived histamine and methylhistamine, all of which are increased in patients with IC. This goal appeared important because IC is a bladder disorder which occurs almost exclusively in women, and is characterized by polyuria, nocturia and pelvic pain, which worsen perimenstrually.


METHODS
Biopsies from six patients with IC and four control patients were analysed blindly for the presence of oestrogen receptors (OR) using both custom-made and commercially available antibodies against OR.


RESULTS
Bladder MC alone were shown to express high-affinity OR and there was a higher number of such cells present in patients with IC compared with controls. The identity of MC in the bladder was documented with immunohistochemistry for tryptase. OR were also identified in human MC (HMC-1), a MC line kept in culture. These steps were necessary because of the unique finding that only MC express OR, in spite of the inflammatory infiltrate present.


CONCLUSIONS
These findings may help to explain why IC occurs primarily in women, why IC and other associated symptoms tend to be worst at the midcycle, and may also suggest that prognostic usefulness of staining bladder biopsies for OR. These results are particularly interesting because oestradiol has been shown to augment MC histamine secretion in response to the neuropeptide, substance P, which may be released in certain neuroinflammatory disorders which have a high prevalence in women, such as IC and irritable bowel syndrome.
Department of Pharmacology, Tufts University School of Medicine, New England Medical Center Hospital, Boston, Massachusetts.
X
X
Pang
M M
MM
Cotreau-Bibbo
G R
GR
Sant
T C
TC
Theoharides
D003556:Cystitis / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008407:Mast Cells / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000032:analysis*; D001743:Urinary Bladder / Q000737:chemistry / Q000473:pathology*
D011960:Receptors, Estrogen