393 Morrill Hall
Hormonal regulation of birth in mammals: physiological effects of the hormones relaxin, estrogen and progesterone.
Relaxin is a protein hormone that is produced and secreted during pregnancy in mammalian species. For more than 20 years Dr. Sherwood's laboratory has devoted research effort toward an understanding of the chemistry and physiology of relaxin. They were the first to isolate and chemically characterize relaxin and did so in two species-the rat and pig. Dr. Sherwood's laboratory then went on to determine the pattern of secretion of relaxin during pregnancy in rats and pigs and to demonstrate that the hormone has vital phsiological roles during pregnancy in both species. Working in concert with estrogen, relaxin promotes growth and softening of both the cervix and the vagina and thereby enables rapid and safe delivery. Relaxin also promotes development of the mammary apparatus and thereby enables normal lactational performance.
During the last six years Dr. Sherwood's laboratory has begun to examine the mechanisms at the cellular and molecular levels whereby relaxin brings about its effects on the cervix and vagina. They have discovered that relaxin promotes a dramatic remodeling of the connective tissue. It reduces the organization and density of collagen fibers, reduces the length of elastin fibers and increases the diameter of arterioles. Relaxin also increases the number of cells in the cervix and vagina during the second half of pregnancy, and Dr. Sherwood's laboratory recently discovered that the hormone does so, at least in part, by acting as a cell survival factor. It inhibits the rate of programmed cell death.
The work in Dr. Sherwood's laboratory has clinical implications. The incidence of induced delivery has risen rapidly in the United States during the last 10 years, and a safe and effective cervical softening agent is needed to prepare the unripe cervix at the induction of delivery. Dr. Sherwood's laboratory has conducted experiments that demonstrated relaxin's clinical potential as a cervical softening agent. BAS Medical is presently conducting clinical trials with human relaxin for the purpose of preparing the cervix for delivery.
Yao, L., Cooke, P.S., Meling, D.M., Shanks,R.D., Jameson, J.L., and Sherwood, O.D. 2010. The effect ofrelaxin on cell proliferation in mouse cervix requires estrogen receptor alpha binding to estrogen response elements in stromal cells. Endocrinology (In press)
Yao, L., Agoulnik, A.L., Cooke, P.S., Meling,D.D., and Sherwood, O.D. 2008 Relaxin acts on stromal cells to promote epithelial and stromal proliferation and inhibit apoptosis in the mouse cervix and vagina. Endocrinology, 149:2072-2079
Lee, H.Y., and Sherwood,O.D. 2005 The effects of blocking the actions of estrogen and progesterone on the rates of proliferation and apoptosis of cervical epithelial and stromal cells during the second half of pregnancy in rats. Biology of Reproduction 73:790-797
Lee. H.Y., Zhao, S., Fields,P.A., and Sherwood, O.D. 2005 The extent to which relaxin promotes proliferation and inhibits apoptosis of cervical epithelial and stromal cellsis greatest during late pregnancy in rats. Endocrinology 146:511-518
Sherwood, O.D. 2004 Relaxin's physiological roles and other diverse functions. Endocrine Reviews 25:205-234
Hsu, S.Y., Nakabayashi, K., Nishi, S., Kumagai, J., Kudo, M., Sherwood,O.D., Hsueh, A.J. 2002 Activation of orphan receptors by the hormone relaxin. Science 295:671-674