Endocrinology, Vol 131, 1841-1847, Copyright © 1992 by Endocrine Society

ARTICLES

Monoclonal antibodies specific for rat relaxin. VII. Passive immunization with monoclonal antibodies throughout the second half of pregnancy prevents development of normal mammary nipple morphology and function in rats

MJ Kuenzi and OD Sherwood
Department of Physiology and Biophysics, University of Illinois, Urbana- Champaign 61801.

We recently demonstrated that relaxin-dependent development of the mammary nipples during the second half of pregnancy is required for pup survival during lactation in the rat. The two related objectives of this investigation were to 1) characterize the effects of endogenous relaxin on the histological modifications that normally occur in the mammary nipples, and 2) test the hypothesis that the cause of lactational failure in relaxin-deficient rats is attributable to failure of the nipples to grow and develop during the second half of pregnancy. Endogenous relaxin was neutralized by daily iv injection of a highly purified monoclonal antibody specific for rat relaxin (MCA1) to intact rats from days 12-22 of pregnancy. Mammary nipples were collected on day 22 of pregnancy and routinely prepared for light microscopy. Tissue cross-sections (6 microns) obtained from the midpoint of mammary nipples were stained with either Gomori's trichrome stain (to visualize collagen) or orcein (to visualize elastin). Nipple size as well as histological characteristics of nipple cross sections were determined by morphometric analysis. MCA1-treated rats were significantly different from controls with the following parameters: shorter length of the nipples; smaller cross-sectional areas of the entire nipple, lactiferous duct lumen, and blood vessels; greater percentage of the analysis field composed of collagen; lower percentage of the analysis field composed of amorphous ground substance; and longer elastin fibers. To test the hypothesis that the cause of lactational failure in relaxin-deficient rats is attributable to the failure of nipples to grow and develop, MCA1 and control rats were cesarean sectioned between 2100-2400 h on day 22 of pregnancy, and lactation was examined using normal foster pups from intact donor females. Unlike pups fostered to controls, pups fostered to MCA1- treated dams failed to grasp the nipples, stimulate PRL release, or have milk in their abdomens. This study demonstrates that endogenous relaxin promotes not only growth, but also modifications of the histological characteristics of the nipple that are consistent with relaxin's effects on the cervix and mammary glands. Additionally, this study provides evidence that lactational failure in relaxin-deficient rats is attributable to the small size and different histology of the mammary nipples, which results in the inability of the pups to attach to the nipple, stimulate PRL release, and obtain milk from the dams.

This article has been cited by other articles:

				D. J. Scott, S. Layfield, Y. Yan, S. Sudo, A. J. W. Hsueh, G. W. Tregear, and R. A. D. Bathgate Characterization of Novel Splice Variants of LGR7 and LGR8 Reveals That Receptor Signaling Is Mediated by Their Unique Low Density Lipoprotein Class A Modules J. Biol. Chem., November 17, 2006; 281(46): 34942 - 34954. [Abstract] [Full Text] [PDF]

				C. S. Samuel Relaxin: Antifibrotic Properties and Effects in Models of Disease Clin. Med. Res., November 1, 2005; 3(4): 241 - 249. [Abstract] [Full Text] [PDF]

				H.-Y. Lee, S. Zhao, P. A. Fields, and O. D. Sherwood The Extent to which Relaxin Promotes Proliferation and Inhibits Apoptosis of Cervical Epithelial and Stromal Cells Is Greatest during Late Pregnancy in Rats Endocrinology, January 1, 2005; 146(1): 511 - 518. [Abstract] [Full Text] [PDF]

				O. D. Sherwood Relaxin's Physiological Roles and Other Diverse Actions Endocr. Rev., April 1, 2004; 25(2): 205 - 234. [Abstract] [Full Text] [PDF]

				S. Zhao, P. A. Fields, and O. D. Sherwood Evidence That Relaxin Inhibits Apoptosis in the Cervix and the Vagina during the Second Half of Pregnancy in the Rat Endocrinology, June 1, 2001; 142(6): 2221 - 2229. [Abstract] [Full Text] [PDF]

				O. D. Sherwood, L. M. Olson, S. Zhao, and H. R. Little Inhibition of Nitric Oxide Synthase Activity Diminishes the Acute Effects of Relaxin on Growth, But Not Softening, of the Cervix in the Rat Endocrinology, July 1, 2000; 141(7): 2458 - 2464. [Abstract] [Full Text] [PDF]

				L. Zhao, P. J. Roche, J. M. Gunnersen, V. E. Hammond, G. W. Tregear, E. M. Wintour, and F. Beck Mice without a Functional Relaxin Gene Are Unable to Deliver Milk to Their Pups Endocrinology, January 1, 1999; 140(1): 445 - 453. [Abstract] [Full Text]

				S. Zhao and O. D. Sherwood Monoclonal Antibodies Specific for Rat Relaxin. X. Endogenous Relaxin Induces Changes in the Histological Characteristics of the Rat Vagina During the Second Half of Pregnancy Endocrinology, November 1, 1998; 139(11): 4726 - 4734. [Abstract] [Full Text] [PDF]

				T. Kohsaka,, G. Min,, G. Lukas,, S. Trupin,, E. T. Campbell,, and O. D. Sherwood Identification of Specific Relaxin-Binding Cells in the Human Female Biol Reprod, October 1, 1998; 59(4): 991 - 999. [Abstract] [Full Text]

				L. L. Burger and O. D. Sherwood Relaxin Increases the Accumulation of New Epithelial and Stromal Cells in the Rat Cervix during the Second Half of Pregnancy Endocrinology, September 1, 1998; 139(9): 3984 - 3995. [Abstract] [Full Text] [PDF]

				A. J. S. Summerlee, D. J. Hornsby, and D. G. Ramsey The Dipsogenic Effects of Rat Relaxin: The Effect of Photoperiod and the Potential Role of Relaxin on Drinking in Pregnancy Endocrinology, May 1, 1998; 139(5): 2322 - 2328. [Abstract] [Full Text] [PDF]

				A. J. S. Summerlee, D. G. Ramsey, and R. S. Poterski Neutralization of Relaxin within the Brain Affects the Timing of Birth in Rats Endocrinology, February 1, 1998; 139(2): 479 - 484. [Abstract] [Full Text] [PDF]