Estrogen-dependent regulation of neurokinin 3 receptor-mediated uterine contractility in the rat

Crane, Linda H., Williams, Melanie J., Nimmo, Alan J., and Hamlin, Gary P. (2002) Estrogen-dependent regulation of neurokinin 3 receptor-mediated uterine contractility in the rat. Biology of Reproduction, 67 (5). pp. 1480-1487.

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The receptors for neurokinin 1 (NK1-R), neurokinin 2 (NK2-R), and neurokinin 3 (NK3-R) are expressed and functionally active in the uterus, promoting strong contractions of the myometrium. Previously, we demonstrated that myometrial contractility activated by the NK-Rs is regulated by estrogen. In the current study, we furthered our investigations of the role of estrogen in the regulation of NK3-R-mediated myometrial contractility. Estrogen promotes both heterologous and homologous desensitization of NK3-R-mediated uterine contractility. In tissue obtained from estrogen-dominated rats (ovariectomized estrogen-treated rats and rats in estrus), the magnitude of uterine contractions decreased in response to consecutive additions of the NK3-R-selective agonist senktide. By addition of the fourth dose of agonist, the contractile response was routinely barely above baseline. In contrast, in tissue obtained from non-estrogen-dominated rats consecutive doses of senktide resulted in contractions of identical magnitude. The homologous desensitization was specific to the NK3-R, and the desensitization of the NK3-R-mediated response did not affect the magnitude or nature of uterine contractions in response to NK1-R or NK2-R activation. Furthermore, heterologous and homologous desensitization of NK3-R-mediated contractility is dependent upon the duration of exposure to estrogen. This complex mechanism appears to be important in intact tissue; capsaicin-mediated release of endogenous neuropeptides resulted in a desensitization of response to subsequent stimulation with senktide in estrogen-dominated uterine tissue.

Item ID: 591
Item Type: Article (Research - C1)
ISSN: 1529-7268
Keywords: Estradiol, Female reproductive tract, Mechanisms of hormone action, Neuropeptides, Uterus
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Copyright 2002 by the Society for the Study of Reproduction, Inc. This journal is available online - use hyperlinks above.

Date Deposited: 09 Oct 2006
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1116 Medical Physiology > 111602 Human Biophysics @ 51%
11 MEDICAL AND HEALTH SCIENCES > 1110 Nursing > 111006 Midwifery @ 49%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920114 Reproductive System and Disorders @ 51%
92 HEALTH > 9205 Specific Population Health (excl. Indigenous Health) > 920507 Womens Health @ 49%
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