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Biology of Reproduction 62, 1005-1009 (2000)
© 2000 Society for the Study of Reproduction, Inc.

Articles

Full Induction of Rat Myometrial 11ß-Hydroxysteroid Dehydrogenase Type 1 in Late Pregnancy Is Dependent on Intrauterine Occupancy1

Brendan J. Waddell2,a, and Peter J. Burtona

a Department of Anatomy and Human Biology, The University of Western Australia, Nedlands, Perth, Western Australia 6907, Australia


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD-1) enzyme catalyses the conversion of the biologically inert glucocorticoid 11-dehydrocorticosterone to active corticosterone (11-oxoreductase activity) in vivo, and it is dramatically up-regulated in uterine myometrium in the days leading up to parturition. 11ß-HSD-1 is likely to enhance local concentrations of glucocorticoid within the myometrium and thus facilitate uterine contractility, but the stimulus for the increase in myometrial 11ß-HSD-1 is unknown. The objective of the present study was to test whether the induction of myometrial 11ß-HSD-1 is dependent on uterine occupancy or systemic hormonal signals of late pregnancy. This involved use of a unilateral pregnancy (ULP) model in which the gravid and nongravid uterine horns are both exposed to the normal systemic hormonal milieu of pregnancy. Western blot analysis showed that the 11ß-HSD-1 signal was only partially induced in the nongravid horn of ULP rats on Day 22 of pregnancy (term: Day 23). Moreover, artificial distension of this nongravid horn had no effect on myometrial 11ß-HSD-1 immunoreactivity or bioactivity at either Day 16 or Day 22 of pregnancy. Removal of fetuses and placentas on Day 18 reduced myometrial 11ß-HSD-1 bioactivity 4 days later, and this effect was not overcome by artificial maintenance of uterine distension. In contrast, after fetectomy at Day 18 (i.e., removal of the fetus but not placenta), myometrial 11ß-HSD-1 bioactivity was largely maintained on Day 22, indicative of placental support for myometrial 11ß-HSD-1 over this period.

In conclusion, our data show that full induction of myometrial 11ß-HSD-1 expression and associated 11-oxoreductase bioactivity late in rat pregnancy is dependent upon intrauterine occupancy. Although the hormonal milieu of late pregnancy appears to stimulate myometrial 11ß-HSD-1 marginally, full induction clearly requires an additional stimulus. Manipulations involving fetectomy and artificial uterine distension indicate that the placenta provides at least part of this stimulus, but uterine stretch does not appear to play a role.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The rat uterus expresses two forms (types 1 and 2) of the enzyme 11ß-hydroxysteroid dehydrogenase (11ß-HSD) in an estrogen-dependent manner [1]. These enzymes catalyze the interconversion of corticosterone, the major glucocorticoid of the rat, and the biologically inactive 11-dehydrocorticosterone, and thereby regulate access of active glucocorticoid to its receptor in target cells (for review see [2]). The 11ß-HSD-1 form of the enzyme was originally purified from rat liver [3], is NADH/P preferring, and acts predominantly as an 11-oxoreductase in vivo [4–6]. In contrast, 11ß-HSD-2 is NAD+ dependent and exhibits exclusively 11ß-dehydrogenase activity [7–9]. We have previously reported that in the days leading up to parturition in the rat there is a dramatic up-regulation in 11ß-HSD-1 expression within uterine myometrium [10], a change likely to enhance local concentrations of active glucocorticoid and thus facilitate uterine contractility and parturition. Although the stimulus for this increase in myometrial 11ß-HSD-1 expression is unknown, three potential factors are the uterine distension associated with the growing fetuses, the concomitant rise in ovarian estrogen secretion, and local endocrine signals originating in the placenta and/or fetus. Uterine distension has previously been shown to up-regulate expression of other genes in the myometrium [11–15], and estrogen provides a potent stimulus for 11ß-HSD-1 expression in the nonpregnant uterus [1] and in placental cells [16]. The objective of the present study, therefore, was to examine whether uterine occupancy or the changing hormonal milieu of late pregnancy can stimulate or maintain myometrial 11ß-HSD-1 expression and associated 11-oxoreductase bioactivity. This involved use of a unilateral pregnancy (ULP) model in which gravid and nongravid uterine horns were exposed to the normal systemic hormonal milieu of pregnancy. Initial experiments showed that the prepartum up-regulation of 11ß-HSD-1 was greatly attenuated in the nongravid horn, and so the effects of artificial distension of this horn were examined. To assess the relative importance of uterine distension and the placenta, myometrial 11ß-HSD-1 bioactivity was measured after artificial distension of the gravid horn from which fetuses and placentas had been removed, as well as after removal of the fetus but not the placenta (fetectomy).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Animals and Chemicals

Nulliparous albino Wistar rats, 3–5 mo old, were obtained from the Animal Resources Centre (Murdoch, Australia) and housed as previously described [17]. Rats were mated overnight, and the morning on which spermatozoa were present in a vaginal smear was designated Day 1 of pregnancy. All procedures involving animals were conducted only after approval by the Animal Experimentation Ethics Committee of The University of Western Australia.

Dulbecco's modified Eagle's medium (DMEM) was obtained from Gibco (Glen Waverley, Australia), [1,2,6,7-3H]corticosterone from Amersham Australia (Sydney, Australia), biotinylated SDS molecular weight standards from Sigma Chemical Co. (St. Louis, MO), and thin-layer chromatography (TLC) plates precoated with silica gel 60 F254 from Merck (Darmstadt, Germany). Tritium-labeled 11-dehydrocorticosterone (11-DHC) was prepared from [3H]corticosterone using rat liver microsomes [18], and the purity of both [3H]corticosterone and [3H]11-DHC was maintained at > 95% by TLC repurification.

Surgical Procedures

ULP was achieved by ligation of one uterotubal junction on Day 2 of pregnancy under halothane/nitrous oxide anesthesia. The nonpregnant horn of ULP rats was distended on Day 21 of pregnancy by insertion and inflation (with 150–250 µl fluid) of a balloon catheter (8 Fr/Ch silicone, double lumen pediatric catheter; Folysil Catheters, Porges, France) at the ovarian end. For uterine distension on Day 15, however, the lumen of the nongravid uterine horn was too narrow to accommodate the catheter, so distension was achieved by injection of saline. This involved ligation of the nongravid horn midway along its length so that distended and nondistended portions were formed, and the distension appeared to be fully maintained over 24 h (i.e., to the morning of Day 16). To examine the effect of the conceptus on myometrial 11ß-HSD-1, all fetuses and placentas were removed from one uterine horn on Day 18 of pregnancy as previously described [19], and a portion of this horn was distended with a balloon catheter until collection of myometrium on Day 22. In a separate experiment, three fetuses were removed from one uterine horn on Day 18 and the placentas left intact as previously described [20]; the myometrium directly surrounding the placenta after fetectomy was collected on Day 22. To achieve maximal uterine distension in each of the above models, the uterine wall was initially distended to the point of blood flow occlusion in superficial vessels, then reduced slightly until this blood flow was restored.

Tissue Collection and Measurement of 11ß-HSD Bioactivity

Myometrial 11-oxoreductase activity was measured as previously described [10]; briefly, both uterine horns were removed from anesthetized rats (halothane/nitrous oxide) at Day 16 or 22 of pregnancy (parturition usually occurs on Day 23). When present, fetuses, placentas, or balloon catheters were removed; the myometrium was isolated by scraping the entire luminal surface of the uterus. When artificial distension of the nongravid uterine horn was employed, myometrium was obtained from both the distended and nondistended portions of the same horn. Myometrium was placed immediately in ice-cold DMEM (with additives), cut into 1- to 2-mm3 fragments using fine scissors, and rewashed in DMEM. Duplicate incubations of myometrial fragments (50 mg) were then performed with 0.2 µCi of [3H]11-DHC in a final volume of 1 ml DMEM for 6 h. Samples were extracted twice with diethyl ether and [3H]corticosterone and [3H]11-DHC isolated by TLC (chloroform:ethanol, 96:4). Each was quantified using liquid scintillation spectrometry, and the percentage conversion was calculated from the relative amounts of substrate and product. Blank incubations (no tissue) were carried out to determine nonspecific interconversion, which was routinely less than 2%; data from experimental incubations were adjusted accordingly.

Western Blot Analysis

Myometrial samples were collected as described above and homogenized in 4 volumes 10 mM sodium phosphate buffer (pH 7.0) containing 0.25 M sucrose, 1 µM EDTA, 1 µM PMSF, and 100 µg/ml trypsin inhibitor. Microsomes were recovered by sequential centrifugation and subjected to Western blot analysis using an antiserum (RAH 13; final concentration 0.45 µg/ml) raised against a synthetic peptide derived from rat 11ß-HSD-1 [21] (kindly provided by Dr. Z. Krozowski, Baker Institute for Medical Research, Melbourne, Australia). The method employed a Vectastain Elite ABC kit (Vector Laboratories, Burlingame, CA) as previously described [10], except that the 11ß-HSD-1 signal was visualized using a chemiluminescence detection kit (SuperSignal Substrate, Western Blotting; Pierce Chemical, Rockford, IL). Blots were placed against autoradiographic film (Kodak XAR film; Eastman Kodak, Rochester, NY) for 1 min, and the resultant images were quantitated by densitometry using NIH (Bethesda, MD) Image analysis version 1.61.

Statistical Analysis

Differences in 11-oxoreductase bioactivity and 11ß-HSD-1 immunoreactivity among myometrial samples from unilaterally pregnant and nonpregnant rats were assessed by one-way ANOVA and least significant difference (LSD) tests [22]. Paired comparisons of 11-oxoreductase activity or 11ß-HSD-1 immunoreactivity within animals were made with either paired t-tests or two-way ANOVA/LSD tests [22].


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
11ß-HSD-1 Protein Expression and 11-Oxoreductase Bioactivity in ULP Rats (Figs. 1 and 2)

Western blot analysis demonstrated the presence of a 34-kDa 11ß-HSD-1 immunoreactive band in myometrium from the gravid horn of Day 22 ULP rats, with a comparable but far less intense band detectable in the nongravid horn. Immunoreactivity was barely detectable, however, in myometrium from rats at postestrus of the cycle (Fig. 1). Quantitative analysis confirmed that the myometrial 11ß-HSD-1 signal was maximal in the gravid horn of ULP rats, minimal in nonpregnant rats, and intermediate in the nongravid horn of ULP rats (Fig. 2). Interestingly, an additional immunoreactive band of higher molecular mass (approximately 50 kDa) was present in myometrium from postestrous rats and in the nongravid horn of ULP rats, but not in myometrium from the gravid horn (Fig. 1). Also, a band of approximately 21 kDa was evident in myometrium from nonpregnant rats and from the nongravid horn of ULP rats. Consistent with the overall pattern of 11ß-HSD-1 immunoreactivity, conversion of [3H]11-DHC to [3H]corticosterone (11-oxoreductase activity) was evident in myometrial fragments from the gravid and nongravid horns of ULP rats on Day 22 of pregnancy (Fig. 2). This activity, however, was markedly lower (P < 0.01, paired t-test) in myometrium from the nongravid horn as compared with the gravid horn of ULP rats, and was comparable to that in myometrium of postestrous rats.



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  		FIG. 1. Western blot analysis of 11ß-HSD-1 protein in myometrium from gravid (PG) and nongravid (PNG) horns of ULP rats, and in myometrium from nonpregnant (NP) rats at postestrus of the cycle



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  		FIG. 2. Quantitative analysis of 11ß-HSD-1 immunoreactivity and 11-oxoreductase bioactivity in myometrium from gravid and nongravid horns of Day 22 pregnant rats, and from nonpregnant rats at postestrus of the cycle. Values are the means ± SEM (n = 3–6 per group), and those without common notations differ significantly (P < 0.05, one-way ANOVA)

Effect of Uterine Distension on 11-Oxoreductase Activity and 11ß-HSD-1 Protein Expression (Figs. 3, 4, and 5)

Myometrial 11-oxoreductase bioactivity was not altered by artificial uterine distension of the nongravid horn of ULP rats from Day 15 to 16 of pregnancy. Thus, myometrial bioactivity in the distended horn of ULP rats was substantially lower (P < 0.001, paired t-test) than that in the gravid horn, but it was comparable to that in the nondistended portion of the same horn (Fig. 3). Similarly, artificial uterine distension from Day 21 to 22 had no apparent effect on myometrial 11-oxoreductase activity in the nongravid horn of ULP rats. However, 11-oxoreductase bioactivity at Day 22 was higher (P < 0.05, unpaired t-tests) in all three tissues (gravid, nongravid, and distended nongravid myometrium) as compared with respective tissues at Day 16 (Fig. 3). Western blot analysis confirmed this overall pattern of bioactivity, with artificial distension having no apparent effect on myometrial 11ß-HSD-1 immunoreactivity at either Day 16 or 22 (Fig. 4).



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  		FIG. 3. 11-Oxoreductase bioactivity in myometrium from Day 16 and Day 22 ULP rats. Myometrial samples were obtained from the gravid and nongravid horns, and from a portion of the nongravid horn distended for 24 h (NGD). Values are the means ± SEM (n = 5 per group), and on each day of pregnancy those values without common notations differ significantly (P < 0.05, two-way ANOVA)



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  		FIG. 4. Quantitative analysis of 11ß-HSD-1 immunoreactivity in myometrium from Day 16 and Day 22 ULP rats. Myometrial samples were obtained from the gravid and nongravid horns, and from a portion of the nongravid horn distended for 24 h (NGD). Values are the means ± SEM (n = 3 per group), and on each day of pregnancy those values without common notations differ significantly (P < 0.05, two-way ANOVA)

The effects of uterine distension were also examined over Days 18–22 after evacuation of one uterine horn (removal of all fetuses and placentas). Enzyme activity (11-oxoreductase) in the nondistended portion of the evacuated horn was less than that in the intact horn of the same animal (P < 0.001, two-way ANOVA and LSD test; Fig. 5). Distension of the evacuated horn for 4 days, however, had no effect on 11-oxoreductase activity (Fig. 5).



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  		FIG. 5. 11-Oxoreductase bioactivity in myometrium on Day 22 after removal on Day 18 of fetuses and placentas with (Evacuated/distended) or without (Evacuated) artificial distension (n = 4; left) or fetuses only (Fetectomized; n = 3; right). Values are the means ± SEM. In the left panel, those values without common notations differ significantly (P < 0.01, two-way ANOVA and LSD test); *P < 0.05 compared with value in the evacuated horn shown on the left (unpaired t-test)

Effect of Fetectomy on Myometrial 11-Oxoreductase Bioactivity (Fig. 5)

After fetectomy (removal of the fetus but not the placenta) at Day 18, 11-oxoreductase activity in the surrounding myometrium on Day 22 did not differ significantly from that in the intact horn of the same animal (P < 0.05, paired t-test; Fig. 5). Moreover, myometrial 11-oxoreductase activity after fetectomy was higher than that following removal of both the fetus and placenta (P < 0.05, unpaired t-test; Fig. 5).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Myometrial expression of the glucocorticoid-metabolizing enzyme 11ß-HSD-1 is dramatically up-regulated in the final days of rat pregnancy, reaching peak levels 1 day prior to parturition [10]. The present study shows that this increase is dependent on intrauterine occupancy, since myometrial 11ß-HSD-1 was only partially induced in the nongravid horn of ULP rats and was not up-regulated by uterine distension. Removal of the placenta and fetus in late pregnancy markedly reduced myometrial 11ß-HSD-1 bioactivity, and this reduction could not be overcome by artificial maintenance of uterine distension. Finally, if the placenta was left intact (in the absence of the fetus), myometrial 11ß-HSD-1 bioactivity was largely maintained, suggesting that the normal rise in myometrial 11ß-HSD-1 is locally stimulated by the placenta.

The initial observation that the systemic hormonal changes of late pregnancy only partially induced myometrial 11ß-HSD-1 expression in the nongravid horn of ULP rats indicates that some other endocrine or physical signal is required for full induction. The massive distension of the uterus caused by the rapidly growing fetuses provided one possibility in this regard, particularly as other genes in the myometrium are induced in this way [11–15]. However, artificial uterine distension for 24 h in our ULP model failed to enhance the induction of 11ß-HSD-1 expression. Distension for this period of time is likely to have provided a sufficiently long stimulus, since induction of myometrial parathyroid hormone-related peptide by distension has been observed within 4 h [14]. Moreover, removal of fetuses and placentas at Day 18 markedly reduced 11ß-HSD-1 bioactivity at Day 22, and this effect could not be overcome by artificial maintenance of uterine distension via a balloon catheter over the following 4 days. Collectively, these observations suggest that full induction of myometrial 11ß-HSD-1 expression requires a local intrauterine, endocrine/paracrine stimulus in addition to the changing hormonal milieu of pregnancy. This contention is supported by our observation that after removal of the fetus but not the placenta (fetectomy) on Day 18, myometrial 11ß-HSD-1 bioactivity was maintained at a level not significantly different from that in the intact horn. This indicates that the placenta plays a key role in the stimulation of myometrial 11ß-HSD-1 expression; and although the nature of this stimulus is unknown, placental secretion of tumor necrosis factor {alpha} (TNF-{alpha}) is a potential candidate. Thus, the rat placenta expresses high levels of TNF-{alpha} late in pregnancy [23], and this cytokine has recently been shown to stimulate 11-oxoreductase bioactivity in cultured glomerular mesangial cells and in the Kiki cell line [24]. Interestingly, 11ß-HSD-1 immunoreactivity is also very high in the reformed uterine luminal epithelium late in pregnancy [10], at which time these cells also express high levels of TNF-{alpha} [24]. Thus, locally produced TNF-{alpha} may also stimulate 11ß-HSD-1 in this epithelium in a paracrine or autocrine fashion.

The clearly higher level of myometrial 11ß-HSD-1 immunoreactivity in the nongravid horn in ULP rats compared with the nonpregnant uterus suggests that systemic hormonal signals of late pregnancy do have some stimulatory effect on 11ß-HSD-1 expression. Estrogen may well contribute to this stimulation, since it up-regulates 11ß-HSD-1 expression in the uterine epithelium in nonpregnant rats [1] and in placental cells [16], and ovarian estrogen secretion increases progressively over the second half of rat pregnancy [25] concomitant with the rise in myometrial 11ß-HSD-1. Because estrogen also stimulates expression of the glucocorticoid receptor in sheep myometrium [26], its proposed stimulation of 11ß-HSD-1 could further enhance the biological potency of glucocorticoids in myometrium at term.

The absence of an increase in myometrial 11-oxoreductase activity associated with the higher levels of immunoreactive 11ß-HSD-1 may simply reflect bioassay insensitivity, but this seems unlikely given the very small but statistically significant differences in bioactivity detected between Days 16 and 22 in all tissues examined. Rather, this apparent inconsistency may reflect the coexpression of 11ß-HSD-2 in myometrium, which we recently observed throughout rat pregnancy (i.e., 11ß-HSD-2 mRNA, protein, and bioactivity). Interestingly, myometrial 11ß-HSD-2 bioactivity levels fell with the onset of pregnancy and immediately returned to prepregnancy levels postpartum (unpublished results). Because 11ß-HSD-2 acts exclusively as an 11ß-dehydrogenase, back conversion of corticosterone to 11-DHC may result in a slight underestimate of 11-oxoreductase activity in our assay system; this effect is likely to be greater in the nongravid horn given the pattern of myometrial 11ß-HSD-2. Thus, despite the very close relationship between 11ß-HSD-1 mRNA and protein and 11-oxoreductase activity previously observed in myometrium over the course of pregnancy [10], changes in 11ß-HSD-2 expression may have slightly perturbed estimates of myometrial 11-oxoreductase activity in the present study. Nevertheless, the use of this tissue fragment assay clearly remains the best option for measurement of 11-oxoreductase activity, since this activity is consistently lost in conventional in vitro assay systems employing tissue homogenates [17, 27].

The overall pattern of myometrial 11ß-HSD-1 expression identified by Western blot analysis generally paralleled the pattern of bioactivity. Thus, a 34-kDa immunoreactive band was evident in all myometrial samples but was clearly maximal in the gravid myometrium. A second immunoreactive band of approximately 50 kDa was observed in all myometrial samples from nonpregnant rats and the nongravid horns of ULP rats, and two lower molecular mass bands (approximately 21 kDa) were apparent in some samples. Obeyesekere et al. [21], using this same 11ß-HSD-1 antiserum, observed a combination of the 34-kDa band and higher molecular mass species (including the approximately 50 kDa observed in the present study) in CHOP cells transfected with mutated 11ß-HSD-1 [21]. Interestingly, our data show that the 50-kDa band was effectively lost with up-regulation of the 34-kDa species in late-pregnant myometrium, possibly indicative of differential posttranslational processing of 11ß-HSD-1.

In conclusion, this study shows that myometrial 11ß-HSD-1 expression and the associated 11-oxoreductase bioactivity are markedly reduced in the absence of the fetus and placenta during late pregnancy in the rat. Although the hormonal milieu of late pregnancy provides some stimulation of myometrial 11ß-HSD-1, full induction clearly requires an additional stimulus. Experiments with fetectomy and artificial uterine distension models indicate that placental signals, but not uterine stretch, provide at least part of this additional stimulus near term.


   ACKNOWLEDGMENTS
 
We thank Dr. Zig Krozowski for generously providing the 11ß-HSD-1 antiserum and Ms. Sue Hisheh for assistance with Western blot analyses.


   FOOTNOTES
 
First decision: 31 August 1999.

1 This work was supported by a grant obtained from the National Health and Medical Research Council of Australia (Project Grant 970132). Back

2 Correspondence. FAX: 61 8 9380 1051; bwaddell{at}anhb.uwa.edu.au Back

Accepted: November 22, 1999.

Received: July 13, 1999.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Burton PJ, Krozowski ZS, Waddell BJ. Immunolocalisation of 11ß-hydroxysteroid dehydrogenase types 1 and 2 in rat uterus: variation across the estrous cycle and regulation by estrogen and progesterone. Endocrinology 1998; 139:376–382.[Abstract/Free Full Text]
  2. Stewart PM, Krozowski ZS. 11ß-Hydroxysteroid dehydrogenase. Vitam Horm 1999; 57:249–324.[Medline]
  3. Lakshmi V, Monder C. Purification and characterization of the corticosteroid 11ß-dehydrogenase component of the rat liver 11ß-hydroxysteroid dehydrogenase complex. Endocrinology 1988; 123:2390–2398.[Abstract/Free Full Text]
  4. Duperrex H, Kenouch S, Gaeggeler HP, Seckl JR, Edwards CRW. Rat liver 11ß-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid encodes oxoreductase activity in a mineralocorticoid responsive toad bladder cell line. Endocrinology 1993; 132:612–619.[Abstract/Free Full Text]
  5. Low SC, Chapman KE, Edwards CRW, Seckl JR. "Liver-type" 11ß-hydroxysteroid dehydrogenase cDNA encodes reductase but not dehydrogenase activity in intact mammalian COS-7 cells. J Mol Endocrinol 1994; 13:167–174.[Abstract/Free Full Text]
  6. Jamieson PM, Chapman KC, Edwards CRW, Seckl JR. 11ß-Hydroxysteroid dehydrogenase is an exclusive 11ß-reductase in primary cultures of rat hepatocytes: effect of physicochemical and hormonal manipulations. Endocrinology 1995; 136:4754–4761.[Abstract]
  7. Rusvai E, Naray-Fejes-Toth A. A new isoform of 11-beta-hydroxysteroid dehydrogenase in aldosterone target cells. J Biol Chem 1993; 268:10717–10720.[Abstract/Free Full Text]
  8. Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS. Cloning and tissue distribution of the human 11ß-hydroxysteroid dehydrogenase type 2 enzyme. Mol Cell Endocrinol 1994; 105:R11-R17.
  9. Krozowski ZS, Provencher PH, Smith RE, Obeyesekere VR, Mercer WR, Albiston AL. Isozymes of 11ß-hydroxysteroid dehydrogenase: which enzyme endows mineralocorticoid specificity? Steroids 1994; 59:116–120.
  10. Burton PJ, Dharmarajan AM, Hisheh S, Waddell BJ. Induction of myometrial 11ß-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid and protein expression late in rat pregnancy. Endocrinology 1996; 135:5700–5706.
  11. Csapo AI. The effects of ovariectomy and stretch on the regulatory profile and activity of the uterus. Prostaglandins 1977; 13:965–973.[CrossRef][Medline]
  12. Douglas AJ, Clarke EW, Goldspink DF. Influence of mechanical stretch on growth and protein turnover of rat uterus. Am J Physiol 1988; 254:E543-E548.
  13. Wathes DC, Porter DG. Effect of uterine distension and oestrogen treatment on gap junction formation in the myometrium of the rat. J Reprod Fertil 1982; 65:497–505.[Abstract/Free Full Text]
  14. Daifotis AG, Weir EC, Dreyer BE, Broadus AE. Stretch-induced parathyroid hormone-related peptide gene expression in the rat uterus. J Biol Chem 1992; 267:23455–23458.[Abstract/Free Full Text]
  15. Vacca G, Battaglia A, Ferro R, Grossini E, Mary DA, Molinari C, Surico N. The effect of distension of the uterus on plasma renin activity (PRA) in anaesthetized pigs. J Auton Nerv Syst 1998; 73:193–169.[CrossRef]
  16. Pepe GJ, Davies WA, Dong KW, Luo H, Albrecht ED. Cloning of the 11ß-hydroxysteroid dehydrogenase (11ß-HSD)-2 gene in the baboon: effects of estradiol on promoter activity of 11ß-HSD-1 and-2 in placental JEG-3 cells. Biochim Biophys Acta 1999; 1444:101–110.[Medline]
  17. Waddell BJ, Bruce NW, Olynyk JK. Independence of ovarian progesterone secretion rate from arterial progesterone concentrations in the pregnant rat. J Endocrinol 1982; 94:61–65.[Abstract/Free Full Text]
  18. Burton PJ, Waddell BJ. 11ß-Hydroxysteroid dehydrogenase in the rat placenta: developmental changes and the effects of altered glucocorticoid exposure. J Endocrinol 1994; 143:505–513.[Abstract/Free Full Text]
  19. Olynyk JK, Bruce NW, Waddell BJ. The acute effect of placentectomy and hysterectomy on peripheral plasma progesterone levels and ovarian progesterone secretion in the pregnant rat. J Endocrinol 1983; 98:71–77.[Abstract/Free Full Text]
  20. Waddell BJ, Benediktsson R, Brown RW, Seckl JR. Tissue specific messenger ribonucleic acid expression of 11ß-hydroxysteroid dehydrogenase types 1 and 2 and the glucocorticoid receptor within rat placenta suggests exquisite local control of glucocorticoid action. Endocrinology 1998; 139:1517–1523.[Abstract/Free Full Text]
  21. Obeyesekere VR, Trzeciak WH, Li KZ, Krozowski ZS. Serines at the active site of 11ß-hydroxysteroid dehydrogenase type I determine the rate of catalysis. Biochem Biophys Res Commun 1998; 250:469–473.[CrossRef][Medline]
  22. Snedecor GW, Cochran WG. Statistical Methods, ed 8. Ames, IA: Iowa State University Press; 1989.
  23. Yelavarthi KK, Chen HL, Yang Y, Cowley BD, Fishback JL, Hunt JS. Tumor necrosis factor-{alpha} mRNA and protein in rat uterine and placental cells. J Immunol 1991; 146:3840–3848.[Abstract]
  24. Escher G, Galli I, Vishwanath BS, Frey BM, Frey FJ. Tumor necrosis factor alpha and interleukin 1 beta enhance the cortisone/cortisol shuttle. J Exp Med 1997; 186:189–198.[Abstract/Free Full Text]
  25. Taya K, Greenwald GS. In vivo and in vitro ovarian steroidogenesis in the pregnant rat. Biol Reprod 1981; 25:683–691.[Abstract]
  26. Wu WX, Derks JB, Nathanielsz PW. Effects of glucocorticoids on estrogen receptor messenger ribonucleic acid in the pregnant ovine myometrium in vivo and in vitro. Biol Reprod 1996; 54:230–241.[Abstract]
  27. Lopez-Bernal A, Anderson ABM, Turnbull AC. Cortisol:cortisone interconversion by human decidua in relation to parturition: effect of tissue manipulation on 11ß-hydroxysteroid dehydrogenase activity. J Endocrinol 1982; 93:141–149.[Abstract/Free Full Text]



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