Title

Sensitivity of myometrium to CGRP changes during gestation

Date of Award

1998

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Physiology and Biophysics

First Committee Member

G. Dahl, Committee Chair

Abstract

The uterus is innervated by calcitonin gene-related peptide (CGRP) immunoreactive neurons, and CGRP inhibits spontaneous and evoked contractions in the uterus and fallopian tubes. Using isometric force measurements on myometrial strips, it was determined that the sensitivity of the myometrium to CGRP is dependent on the gestational and hormonal state of the animal. CGRP inhibition of acetylcholine (ACh)-induced contractions was drastically reduced at parturition compared to earlier stages of gestation in mice. In addition, the inhibitory effect of CGRP varied during the estrous cycle. This inhibition was the lowest at estrus, then gradually increased as the cycle advanced, and reached a maximum at diestrus.The level of inhibition exerted by CGRP paralleled the expression of a novel protein recently implicated in CGRP receptor activation, the CGRP-receptor component protein (CGRP-RCP). The mouse CGRP-RCP cDNA was isolated from uterus, and expression of the CGRP-RCP was monitored during gestation by northern and western blot analysis. While no significant change in CGRP-RCP mRNA levels during gestation and post partum was found, CGRP-RCP protein was greatly diminished at parturition. This diminution correlated with the loss of CGRP inhibition of ACh-induced contractions at term, observed in the force experiments.The signal transduction pathway whereby CGRP inhibits myometrial contractility, including the expression of CGRP-RCP, appears to be regulated by the hormonal events of the estrus cycle and gestation. A role for CGRP and CGRP-RCP in modulation of myometrial smooth muscle contractility during gestation is suggested.

Keywords

Biology, Molecular; Biophysics, Medical

Link to Full Text

http://access.library.miami.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:9904650