| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Articles |
Department of Molecular and Integrative Physiology (G.M., M.G.H., R.L.J., R.J.W., O.D.S.) and the College of Medicine (O.D.S.), University of Illinois-Urbana-Champaign, Urbana, Illinois 61801
Address all correspondence and requests for reprints to: Dr. O. D. Sherwood, Department of Molecular and Integrative Physiology, University of Illinois-Urbana-Champaign, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, Illinois 61801. E-mail: od-sherw{at}uiuc.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Three groups of pregnant gilts were used: sham-ovariectomized controls (group C; n = 8), ovariectomized progesterone-treated (group OP; n = 6), and ovariectomized progesterone- plus relaxin-treated (group OPR; n = 7). Gilts were either sham ovariectomized or ovariectomized on day 40 of gestation. Hormone replacement therapy with progesterone (group OP), progesterone plus relaxin (group OPR), or hormone vehicles (group C) began on day 38 (progesterone) or day 40 (relaxin) and continued until day 110. On day 110, the vagina and uterus were collected, and wet weight, dry weight, and percent hydration were determined. Small pieces (2–3 cm3) of the vagina and uterus from groups C and OP were frozen and cryosectioned for the immunohistochemical localization of relaxin-binding sites.
Relaxin promoted growth of both the vagina and uterus. The wet weights of both the vagina and uterus in relaxin-deficient gilts (group OP) were lower (P < 0.05) than those in controls (group C), and relaxin replacement therapy (group OPR) restored the wet weights of both tissues to values that did not differ from those in controls. The mean dry weights and percent hydrations in the vagina and uterus did not differ among treatments. Immunohistochemical localization studies in the vagina and uterus demonstrated that specific and saturable binding of relaxin was localized in the same cell types of both tissues, namely epithelial cells (luminal in vagina, and both luminal and glandular in uterus), smooth muscle cells (both circular and longitudinal in vagina, and myometrial in uterus), and cells associated with blood vessels.
In conclusion, this study provides evidence that circulating relaxin promotes growth of both the vagina and uterus during pregnancy in the pig. Furthermore, this study provides evidence that both the vagina and uterus contain specific and saturable relaxin-binding sites in epithelial cells, smooth muscle cells, and cells associated with blood vessels. We conclude that these cells probably initiate relaxin’s effects on the vagina and uterus of the pregnant pig.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
In gilts, the corpora lutea are the source of the relaxin secreted into the peripheral circulation during pregnancy (1). Whereas a portion of the relaxin produced by the corpora lutea accumulates in dense membrane-bound cytoplasmic granules (1), relaxin is also secreted throughout nearly all of the approximately 114-day gestation period. Plasma relaxin immunoactivity is detectable within 1 week of conception and remains below 1 ng/ml until day 40 of pregnancy. Plasma relaxin increases progressively to about 10 ng/ml on day 110 of pregnancy and then surges to maximal levels of about 60–250 ng/ml when degranulation of the luteal cells occurs at luteolysis during the 2 days before birth (10, 11, 12). Circulating endogenous relaxin has been demonstrated to have two physiological roles during the last third of gestation in gilts. Relaxin promotes marked growth and softening of the cervix (13) and thereby enables rapid and safe delivery of the piglets (14). Relaxin also promotes marked growth of the mammary lobulo-alveolar tissue (6).
There is reason to hypothesize that circulating endogenous relaxin has at least two additional roles in the reproductive tract during pregnancy in pigs. Whereas there is presently no evidence in pigs, relaxin may promote growth of the vagina in this species. Recent studies demonstrated that endogenous relaxin plays a major role in promoting growth of the vagina during the second half of pregnancy in rats (15, 16). During the last several years it was also demonstrated that porcine relaxin has uterotropic effects in pigs. When porcine relaxin was administered to nonpregnant gilts (17, 18, 19, 20) or to pregnant gilts on days 6–11 of gestation (21), wet weight (17, 18, 19, 20, 21) and water content (17, 19, 21) increased.
It is not known whether circulating endogenous relaxin has physiological effects on the vagina or uterus during pregnancy in pigs. Accordingly, the present study determined whether circulating relaxin promotes growth of these two portions of the reproductive tract during the last two thirds of gestation in ovariectomized gilts. Finding that it does, this study also employed an in vitro immunohistochemical localization technique (22) to identify specific cell types that bind relaxin in both the vagina and uterus.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
120 kg) obtained from the Swine
Research Center at the University of Illinois Urbana-Champaign (UIUC),
were mated at estrus (day 0). Throughout gestation, animals were housed
in individual confinement crates. Gilts were fed once daily a diet of
corn and soybean (12% protein) and were allowed free access to
water.
Treatments
Gilts were assigned to one of three treatment groups, as shown
in Fig. 1
. Treatments consisted of control gilts (group
C; n = 8), ovariectomized progesterone-treated gilts (group OP;
n = 6), and ovariectomized progesterone- plus relaxin-treated
gilts (group OPR; n = 7). The animal experimentation described in
this report was reviewed and approved by the UIUC laboratory animal
care advisory committee.
|
Hormone replacement therapy
Hormone doses were selected to provide plasma levels resembling
those during pregnancy in intact pregnant gilts (5, 13). Progesterone
(50 mg/injection; Sigma Chemical Co., St. Louis, MO) or progesterone
vehicle (2 ml corn oil/injection; Eastman Kodak, Rochester, NY)
injections, which began at 0600 h on day 38 of gestation and
continued at 12-h intervals until 0600 h on day 110, were
administered im in the neck. Highly purified porcine relaxin (23) or
relaxin vehicle (2 ml physiological saline) was injected im in the neck
at 6-h intervals beginning at 1200 h on day 40 of gestation and
continuing until 0600 h on day 110. Doses of relaxin per injection
were increased as pregnancy progressed (0.1 mg for days 40–80, 0.25 mg
for days 81–100, and 0.5 mg for days 101–110). As estrogen is
produced by the placenta during pregnancy in pigs, it was not
administered.
Tissue collection
Gilts were killed within 2 h of the last hormone injection
on day 110 of gestation by electrical stunning and exsanguination at
the UIUC Meat Science Laboratory. The entire reproductive tract was
removed, and the fetuses were removed from the uterus, counted,
cleaned, and weighed. The uterus, uterine (cephalic) portion of the
cervix, vaginal (caudal) portion of the cervix, and vagina were
separated with a filleting knife. The uterine and vaginal portions of
the cervix and the vagina were trimmed of excess tissue and immediately
weighed. Segments (2 x 6 cm) from each of the three portions
of the lower reproductive tract were weighed, frozen on dry ice, and
stored at -25 C for dry weight and percent hydration determinations.
The uteri and their placental contents were placed in sealed plastic
bags and allowed to sit in a walk-in cold room (4 C) overnight to
facilitate the removal of placentas from the uteri. Immediately after
removal of the placentas, both uteri and placentas were weighed. A
segment (2 x 6 cm) from each uterus was weighed, frozen on dry
ice, and stored at -25 C for dry weight and percent hydration
determinations.
Within 5 min of removal of the reproductive tract, small pieces (2–3 cm3) of the uteri and the vaginas from group C and group OP gilts were individually placed in Peel-A-Way plastic embedding molds (Polysciences, Warrington, PA) containing Tissue-Tek OCT compound (Miles Scientific, Elkhart, IN), frozen in liquid nitrogen, and stored at -70 C until sectioning.
Determination of tissue weights
Wet weights of the uterus and placentas were determined using a
Fisher model 2–116 balance (Fisher Scientific, Pittsburgh, PA), and
wet weights of both portions of the cervix and the vagina were
determined using a Mettler model P1200 balance (Mettler Instrument,
Princeton, NJ). Fetal weights were determined using a Durand model
8,000 balance (Durand Scales, Batavia, IL).
To determine the dry weights and water contents (percent hydration) of cervical (positive control), vaginal, and uterine tissues, 2 x 6-cm segments of each tissue were placed in vials and dried for 1 week in an FTS Systems Tri-philizer (Stone Ridge, NY). Tissues were reweighed to determine the dry weight and water content (percent hydration) of each segment.
Preparation and characterization of biotinylated relaxin
Porcine relaxin was isolated as described by Sherwood and
O’Byrne (23), and it was biotinylated by a modification (22, 24) of
the procedure described by Büllesbach and Schwabe (25). In brief,
porcine relaxin was dissolved in 0.2 M
N-methylmorpholine-HCl buffer (pH 7.5) at a final
concentration of 2 µmol/ml. To supply the biotinylating reagent in
excess, 10 molar equivalents of biotinyl-
-aminocaproic
acid-N-hydroxysuccinimide ester (Sigma Chemical Co., St.
Louis, MO) in dimethylformamide at a concentration of 100 µmol/ml
were added to the relaxin. The reaction mixture was stirred at room
temperature for 4 h, then stopped by the addition of acetic acid
until a 1 M acetic acid solution was obtained. The contents
of the reaction mixture were separated from the
biotinyl--aminohexanoyl-relaxin (biotinylated relaxin) by
ultrafiltration using an Amicon model 402 stirred ultrafiltration
apparatus with a Diaflo Ultrafilter type YM1 membrane (mol wt cut-off
1000; Amicon, Beverly, MA). The N-methylmorpholine-HCl
buffer and acetic acid were replaced with PBS (0.01 M
NaH2PO4 and 0.15 M NaCl, pH 7.4) in
the ultrafiltration unit. The biotinylated relaxin was stored at a
final concentration of 9 nmol/ml at -70 C.
The mean number of biotin molecules per biotinylated relaxin molecule as determined by spectrophotometric 4'-hydroxyazobenzene-2-carboxylic acid (HABA) assay (Pierce Chemical Co., Rockford, IL) was 3.5. Biotinylated relaxin elicited a strong biological response, as determined with the mouse interpubic ligament bioassay (26). The mouse interpubic ligament lengths (mean ± SE) for repository vehicle control (1% L-390 in PBS), 1 µg relaxin, and 1 µg biotinylated relaxin injections were 0.7 ± 0.07, 2.4 ± 0.17, and 2.2 ± 0.18 mm, respectively.
In vitro immunohistochemical localization of relaxin-binding
cells
In vitro immunohistochemical localization of
relaxin-binding cells was conducted as previously described (22). In
brief, frozen sections (8 µm) of vaginal and uterine tissues were cut
on a HR Mark II cryostat (Slee Medical Equipment, London, UK) at -20 C
and thaw-mounted on microscope slides coated with 0.2%
poly-L-lysine (mol wt, 300,000). The tissue slides were
brought to room temperature, and subsequent immunohistochemical
procedures were performed at room temperature. The tissues were
incubated for 30 min in 50 mM glycine in PBS (pH 7.4), and
then incubated for 3 h with blocking buffer 1 [1% BSA fraction
V, 0.2% fish gelatin (Amersham, Arlington Heights, IL), 5% normal pig
serum, and 2 mM NaN3 in PBS]. The tissues were
incubated for 3 h in incubation buffer 1 (1% BSA fraction V,
0.2% fish gelatin, 1% normal pig serum, and 2 mM
NaN3 in PBS) in three different ways. The first treatment
incubated each tissue with biotinylated relaxin probe (0.5
µM) to localize relaxin receptors. The second treatment
incubated each tissue with biotinylated relaxin plus a 2,000-fold
excess of porcine insulin (1 mM; ILETIN II, Eli Lilly Co.,
Indianapolis, IN) to determine the hormonal specificity of binding of
the biotinylated relaxin probe. The third treatment incubated each
tissue with biotinylated relaxin plus a 2,000-fold excess of porcine
relaxin (1 mM) (23) to determine whether there are finite
numbers of relaxin receptors in the tissue. After incubation, tissue
slides were rinsed for 2 h with five changes of wash buffer (1%
BSA fraction V, 0.2% fish gelatin, and 2 mM
NaN3 in PBS). The tissues were then postfixed for 10 min in
2% glutaraldehyde in PBS, rinsed briefly with double distilled water,
and incubated for 30 min in 50 mM glycine. The tissues were
then incubated for 4 h in blocking buffer 2 (1% BSA fraction V,
0.2% fish gelatin, 5% normal goat serum, and 2 mM
NaN3 in PBS), followed by a 4-h incubation with 800 µl
antibiotin IgG conjugated to 1 nm colloidal gold (Auroprobe One
anti-biotin, Amersham) diluted 1:20 with incubation buffer 2 (1% BSA
fraction V, 0.2% fish gelatin, 1% normal goat serum, and 2
mM NaN3 in PBS). The tissues were rinsed for
2 h with five changes of wash buffer and were postfixed in 2%
glutaraldehyde for 10 min. All slides were rinsed with copious amounts
of double distilled water for 30 min before silver intensification of
the gold particles. Silver intensification was performed by incubating
sections in IntenSE M silver solution (Amersham) for 8 min at room
temperature. The slides were rinsed with copious amounts of double
distilled water for 10 min, and the silver intensification was
repeated. The sections were dehydrated in an ascending alcohol series,
cleared in Clear-Rite (Richard Allen, Richland, MI), and coverslipped
using mounting medium (Richard Allen).
Statistics
Data were analyzed by ANOVA, and significant differences among
groups were determined by t test (27).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
shows that there
were no differences in the number of fetuses, fetal weights, or
placental weights among the three treatment groups.
|
). Also consistent with previous findings (13, 28), the
wet weight and percent hydration of the vaginal portion of the cervix
in group OP gilts were lower than those in controls, and replacement
therapy with relaxin restored both parameters to values that were as
high (percent hydration) or higher (wet weight) than those in controls.
It appears that relaxin may also promote increased dry weight of the
vaginal cervix. Whereas the mean dry weight in group OP gilts
(P < 0.1) was not significantly lower than that in
controls, relaxin replacement therapy (group OPR) resulted in greater
mean dry weight than that in relaxin-deficient gilts (group OP; see
Fig. 2).
|
). Whereas the mean dry
weight in group OP gilts tended to be lower than that in groups C and
OPR, ANOVA indicated (P < 0.18) that there were no
significant differences among treatments. There were no differences in
percent hydration among treatments.
|
). Whereas the mean dry weight in group OP
gilts tended to be lower than that in groups C and OPR, ANOVA indicated
(P < 0.1) that there were no significant differences
among treatments. There were no differences in percent hydration among
treatments.
The most pronounced effects of endogenous relaxin on wet weight of the
reproductive tract during pig pregnancy occur in the uterine portion of
the cervix (see Fig. 4).
|
. In both tissues, prominent labeling of
smooth muscle cells (myometrial in the uterus and both longitudinal and
circular in the vagina) and epithelial cells (both luminal and
glandular in the uterus and luminal in the vagina) was observed in
sections incubated with biotinylated relaxin (Fig. 5, A and D).
Labeling of less intensity was also observed in blood vessels. Binding
of the biotinylated relaxin to the vagina and uterus was hormone
specific and saturable. Labeling of the smooth muscle (myometrial,
longitudinal, and circular), epithelium (luminal and glandular), and
blood vessels occurred in sections incubated with biotinylated relaxin
in the presence of a 2000-fold excess of porcine insulin (Fig. 5, B and
E), but not in the presence of a 2000-fold excess of porcine relaxin
(Fig. 5, C and F). There were no apparent differences in relaxin
binding (both distribution and intensity of labeling) either within
each group or between group C and group OP.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The finding that circulating relaxin promotes increased wet weight of the vagina in pregnant gilts is in agreement with our recent report that endogenous relaxin promotes increased wet weight of the vagina in pregnant rats (15, 16). In rats, relaxin also promotes increased dry weight of the vagina (15, 16). Whereas there was a consistent tendency for the vaginal dry weights in relaxin-deficient gilts to be lower than those in relaxin-replete animals, the differences were not statistically significant. The considerable variation associated with vaginal dry weights appears to be attributable to a combination of three factors: 1) an innate difference in vaginal sizes among animals, 2) lack of a clear anatomical feature that enables totally objective judgments regarding the identification of the border between vaginal and cervical tissues, and 3) experimental variation associated with the process of dry weight determinations. The physiological importance of relaxin’s effects on the vagina is presently not known. By promoting growth of the vagina as well as the cervix (13, 28), relaxin may facilitate rapid and safe delivery of the piglets (14).
Endogenous relaxin has not previously been demonstrated to influence uterine weight in any species. The finding that uterine wet weight in relaxin-deficient ovariectomized pregnant gilts is lower than uterine wet weight in both intact controls and ovariectomized gilts treated with relaxin is novel and provides strong support for the view that circulating endogenous relaxin promotes increased wet weight of the uterus in pregnant gilts. The physiological significance of relaxin’s effects on the uterus is not known. Relaxin may assist with the accommodation of the growing fetuses by promoting growth and/or remodeling of the uterus during pregnancy. Although endogenous relaxin does not appear to promote uterine growth in the pregnant rat, morphometric and histological analysis of uteri obtained from ovariectomized estrogen-primed nonpregnant rats demonstrated that highly purified porcine relaxin promoted rapid growth and remodeling of the uterus (29). A dramatic increase in the volume of both the endometrium and the myometrium as well as disorganization of collagen network in the connective tissue layer of both uterine compartments occurred. Relaxin may also protect the fetuses from spontaneous uterine contractions by reducing myometrial contractility (30, 31, 32, 33).
As with the mammary glands and nipples (6, 7), the effects of circulating relaxin on the growth of the uterus during pregnancy differ between pigs and rats. Whereas this study demonstrated that circulating relaxin promotes increased wet weight of the uterus in pregnant gilts, the rat relaxin that is present in high levels in the peripheral blood during the second half of pregnancy (34) does not appear to influence uterine wet weight. Neutralization of endogenous rat relaxin throughout the second half of pregnancy with sufficient monoclonal antibody specific for rat relaxin to inhibit the growth of the cervix did not influence uterine wet weight at term (35).
The finding that the vagina and uterus contain specific relaxin-binding cells not only provides additional evidence that relaxin has direct effects on the vagina and uterus, but also provides insight concerning the cells that mediate relaxin’s effects on these two portions of the reproductive tract. Relaxin binding to epithelial cells, smooth muscle cells, and cells associated with blood vessels in both the vagina and uterus is consistent with the cellular location of relaxin binding in the cervix, mammary glands, and nipples of the pregnant pig (22). These findings indicate that relaxin may promote growth and/or remodeling of several target tissues at least in part by a similar mechanism(s).
In conclusion, this study provides evidence that circulating relaxin promotes growth of both the vagina and uterus during pregnancy in the gilt. Furthermore, this report provides the first evidence that epithelial cells, smooth muscle cells, and cells associated with blood vessels in both the vagina and uterus of the pig contain relaxin-binding sites. These cells probably initiate relaxin’s effects on the vagina and uterus.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received July 1, 1996.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
during late pregnancy.
Endocrinology 104:1716–1721[Medline]
-aminohexanoyl) porcine relaxin. Int J Pept Protein
Res 35:416–423[Medline]
This article has been cited by other articles:
 |
|
 |
|
  P. G. Drewes, H. Yanagisawa, B. Starcher, I. Hornstra, K. Csiszar, S. I. Marinis, P. Keller, and R. A. Word Pelvic Organ Prolapse in Fibulin-5 Knockout Mice: Pregnancy-Induced Changes in Elastic Fiber Homeostasis in Mouse Vagina Am. J. Pathol., February 1, 2007; 170(2): 578 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 W. Yan, A. A. Wiley, R. A. D. Bathgate, A.-L. Frankshun, S. Lasano, B. D. Crean, B. G. Steinetz, C. A. Bagnell, and F. F. Bartol Expression of LGR7 and LGR8 by Neonatal Porcine Uterine Tissues and Transmission of Milk-Borne Relaxin into the Neonatal Circulation by Suckling Endocrinology, September 1, 2006; 147(9): 4303 - 4310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Yan, P. L Ryan, F. F Bartol, and C. A Bagnell Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs. Reproduction, May 1, 2006; 131(5): 943 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. P. Conrad and J. Novak Emerging role of relaxin in renal and cardiovascular function Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R250 - R261. [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]
|
|
|
|
 |
|
 L. T. Goldsmith, G. Weiss, S. Palejwala, T. M. Plant, A. Wojtczuk, W. C. Lambert, N. Ammur, D. Heller, J. H. Skurnick, D. Edwards, et al. Relaxin regulation of endometrial structure and function in the rhesus monkey PNAS, March 30, 2004; 101(13): 4685 - 4689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Lenhart, P. L. Ryan, K. M. Ohleth, S. S. Palmer, and C. A. Bagnell Relaxin Increases Secretion of Tissue Inhibitor of Matrix Metalloproteinase-1 and -2 during Uterine and Cervical Growth and Remodeling in the Pig Endocrinology, January 1, 2002; 143(1): 91 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Lenhart, P. L. Ryan, K. M. Ohleth, S. S. Palmer, and C. A. Bagnell Relaxin Increases Secretion of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 during Uterine and Cervical Growth and Remodeling in the Pig Endocrinology, September 1, 2001; 142(9): 3941 - 3949. [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]
|
|
|
|
 |
|
 L. Zhao, C. S. Samuel, G. W. Tregear, F. Beck, and E. M. Wintour Collagen Studies in Late Pregnant Relaxin Null Mice Biol Reprod, March 1, 2000; 63(3): 697 - 703. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Lenhart, P. L. Ryan, K. M. Ohleth, and C. A. Bagnell Expression of Connexin-26, -32, and -43 Gap Junction Proteins in the Porcine Cervix and Uterus During Pregnancy and Relaxin-Induced Growth Biol Reprod, December 1, 1999; 61(6): 1452 - 1459. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
G. Min and O.D. Sherwood Localization of Specific Relaxin-Binding Cells in the Ovary and Testis of Pigs Biol Reprod, August 1, 1998; 59(2): 401 - 408. [Abstract] [Full Text]
|
|
|
|
|
|
O. D. Sherwood, E. S. Jungheim, J. L. Masferrer, and J. M. Cramer Evidence That Relaxin's Effects on Growth and Softening of the Cervix Are Not Mediated through Prostaglandins in the Rat Endocrinology, March 1, 1998; 139(3): 867 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Ohleth, J. A. Lenhart, P. L. Ryan, S. V. Radecki, and C. A. Bagnell Relaxin Increases Insulin-Like Growth Factors (IGFs) and IGF-Binding Proteins of the Pig Uterus in Vivo Endocrinology, September 1, 1997; 138(9): 3652 - 3658. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
