Uterine Dry Weight Research Articles

Estrogenic Effect of Salvia officinalis Extract on Reproductive Function of Female Mice and Identification of Its Phenolic Content.

Natural Phytoestrogens present in plants are effective hormonal replacement therapy. They are converted to estrogenic substances in the gastrointestinal tract, which is considered as the natural alternative to estrogen substitute treatment for postmenopausal women. Salvia officinalis, a herb traditionally used to ameliorate postmenopausal complications, can provide a safe alternative to synthetic pharmaceuticals for the treatment of menopause. Therefore, it is conceivable to detect the possible estrogenic effect of Salvia Officinalis extract as an estrogen replacement therapy in female mice. Phytochemical, pharmacological, and immune histopathological techniques are adopted in this study. HPLC is used for the identification of extracted constituents of sage herb. The uterotrophic activity of the extract was determined in immature female mice. Moreover, the mean thickness and luminal epithelium and the photomicrographs of the luminal epithelium of the uterus were also studied. HPLC revealed that quercetin is the major extracted constituent (28.6%) of the total components. Saliva officinalis extract produced a significant increase in the uterine dry weight of equal potency to estrogen. The uterus exhibited a significant increase in luminal epithelial cell height (43.3 ± 6.1μm and 36.5 ± 2.5μm) for estradiol and sage extract, respectively, compared with the control group (18.2 ± 3.5μm). Furthermore, the endometrium showed the lining epithelium formed of a single layer of columnar epithelium. The stroma seemed more voluminous with dilated vasculature. Conversely, the myometrium within the uterus was not affected in any of the experimental groups. The sage herbs induced proliferative changes in the uteri of treated mice, which suggest possible estrogenic properties. Saliva officinalis extract can be used as a hormonal replacement for women during menopause and could be further explored for contraceptive use.

Use of 3D Transvaginal Ultrasound in Prediction of the Need to Morcellate in Women Undergoing Laparoscopic Hysterectomy

In light of recent statements from the United States Food and Drug Administration warning against the use of power morcellation of uterine leiomyomas during laparoscopy, we have evaluated the use of preoperative two- (2D) and three- (3D) dimensional transvaginal ultrasound (US) assessment of uterine volume to predict the need for morcellation in women undergoing laparoscopic hysterectomy (LH). This was a prospective observational study performed between October 2008 and November 2011 in a tertiary referral laparoscopic unit. All women scheduled to undergo LH were included and underwent detailed preoperative transvaginal US. Uterine volumes were calculated using 2D-US measurements (ellipsoid formula), and using Virtual Organ Computer-aided AnaLysis (VOCAL™) having acquired 3D-US volumes of the uterus. Age, parity, need to morcellate and final uterine dry weight at histology were recorded. The estimated uterine volumes were then incorporated into a previously published logistic regression model to predict the need to morcellate for both nulliparous and parous women. The probability threshold cut-off of 0.14 (95% sensitivity) was evaluated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratios (LRs). The performance of the models incorporating 2D- and 3D-US calculations were compared with 2D- and 3D-US-generated volumes alone, using receiver-operating characteristics (ROC) curves. Of 76 women who underwent LH during the study period, 79% (n = 60) had complete background and 3D-US data. Their mean age was 43.7 years, 91.7% were parous and 35% underwent morcellation. The greatest uterine volume that did not require morcellation was 404 mL estimated using 3D-US, which corresponded to a uterine volume of 688.8 mL using 2D-US. The smallest uterine volume that required morcellation was 118.9 mL using 3D-US, which corresponded to a uterine volume of 123.4 mL using 2D-US. The 3D-US uterine volume for parous women with a sensitivity of 95% based on ROC-curve analysis was approximately 120 mL, which equated to a predicted probability of morcellation cut-off of 0.14. For this cut-off, specificity was 55.00%, PPV was 51.35%, NPV was 95.65%, LR+ was 2.11 and LR- was 0.09. Areas under the ROC curves for the morcellation logistic regression model were 0.769 (95% CI, 0.653-0.886) and 0.586 (95% CI, 0.419-0.753) using uterine volumes obtained by 3D-US and by 2D-US, respectively, and they were 0.938 (95% CI, 0.879-0.996) and 0.815 (95% CI, 0.681-0.948) using 3D-US and 2D-US volumes alone. In conclusion, the need to morcellate can be predicted preoperatively using 3D-US uterine volumes obtained by transvaginal US with a fair degree of accuracy. Uteri with volumes smaller than 120 mL at 3D-US are very unlikely to require morcellation. The incorporation of 3D-US-estimated uterine volume into the previously published logistic regression model does not seem to confer any significant improvement when compared with 3D-US uterine volume alone to predict the need to morcellate in women undergoing total LH.

Estimation of uterine volume: A comparison between Viewpoint and 3D ultrasound estimation in women undergoing laparoscopic hysterectomy.

Objectives: To assess the three‐dimensional (3D) tool, Virtual Organ Computed‐aided AnaLysis™ (VOCAL) in the calculation of pre‐operative uterine volume and to correlate the measurements with those obtained with Viewpoint, using uterine dry weight (UDW) as the gold standard. Methods: Prospective observational study of women consented for a laparoscopic hysterectomy (LH) at Nepean Hospital between October 2008 and November 2011. All women underwent detailed transvaginal scan (TVS) at the pre‐operative assessment. Two‐dimensional (D) images of the uterus were obtained both in the mid‐sagittal and transverse planes. 3D volumetric acquisitions were also obtained for each uterus in the mid‐sagittal plane. 2D measurements of the uterus in millimetres (Anterio‐Posterior, longitudinal and transverse) were recorded in Viewpoint software package (GE Healthcare ViewPoint, Germany); which then generated an estimated uterine volume (ml) using the ellipsoid formula. The 3D uterine volumetric datasets were reviewed using SonoView Pro and uterine volumes were estimated with off‐line processing using VOCAL™. The gold standard for comparison was UDW in grams (g), measured by the histopathologist at the time of analysis of the LH specimens. The relationship between the estimated uterine volumes and actual UDW was evaluated using correlation analysis. P‐values were calculated to ascertain the significance of these findings; P values &< 0.05 represented statistical significance. Results: 76 women underwent LH during the study period. Complete data were available in 96% (74/76) of cases. The mean age of the women was 43.7 years and 92% were multiparous. The mean Viewpoint uterine volume was 283 ml, the mean VOCAL™ uterine volume was 249 ml and the mean UDW was 295 g. There was a significant correlation between UDW and estimated uterine volumes both for Viewpoint (R = 0.83, P < 0.001) and VOCAL™ (R = 0.97, P < 0.001), respectively. Viewpoint systematically overestimated weight by 43.1 g, whereas VOCAL™ underestimated by an average of 42.4 g, and this difference was statistically significant (P < 0.001). In terms of absolute values, the mean prediction error for VOCAL™ was −18.0 g and for Viewpoint it was 27.6 g (P &< 0.0001). Conclusion: VOCAL™ was found to be significantly more accurate than Viewpoint in the estimation of uterine volumes, and it was better correlated with UDW.

OP03.03: Estimation of uterine volume: A comparison between ViewPoint/Astraia and 3D VOCAL analysis in relation to uterine dry weight

OP03.03: Estimation of uterine volume: A comparison between ViewPoint/Astraia and 3D VOCAL analysis in relation to uterine dry weight

P07.09: Estimation of uterine dry weight from pre‐operative 3D uterine volume ultrasound evaluation in women undergoing total laparoscopic hysterectomy (TLH)

P07.09: Estimation of uterine dry weight from pre‐operative 3D uterine volume ultrasound evaluation in women undergoing total laparoscopic hysterectomy (TLH)

Effects of pulsed or continuous estradiol exposure on uterine growth, histology, gene expression and proliferation in ovariectomised female wistar rats

A wide variety of routes of administration and formulations are employed in estrogen replacement therapy. Recently, an intranasal 17ß-estradiol (E2) spray S21400 (AERODIOL) has been developed. This study was set out to investigate the effects of pulsed estrogen administration compared to continuous therapy, with regard to uterine proliferation. Ovariectomised wistar rats were either treated pulsed or continuously with 1, 4, 10 and 250mg/kg/BW E2 for 10 days. Control groups consisted of ovariectomised and Sham-operated rats. Uterine weight, the height of the uterine epithelium, the expression of Complement 3 gene (C3) and PCNA was determined. Continuous administration of E2 resulted in a dose dependent increase of uterine dry and wet weight and an increase of the height of the uterine epithelium. A dose of 10mg/kg/BW/day resulted in a uterine wet weight comparable to Sham animals but in a thickness of the uterine epithelium of 42mm, compared to 25mm of the Sham animals. Pulsed administration of E2 resulted even in the highest dose administrated in a uterine wet weight of 50% of the Sham animals. The height of the uterine epithelium was stimulated to a maximum of 30mm, even in the highest dose administrated. Pulsed administration of 10 and 250mg/kg/BW/day E2 resulted in a 5-fold induction of C3 mRNA expression compared to Sham animals, whereas the C3 expression in continuously treated animals was induced 10 respectively 15-fold compared to Sham animals. Proliferation in the uterine epithelium, indicated by immunohistochemical analysis of PCNA expression, was stimulated dramatically after continuous administration of 10mg/mg/BW day E2. In contrast, only a faint stimulation of proliferation could be detected in pulsed treated animals. In conclusion our data demonstrate that pulsed administration of E2 resulted in a significantly lower activity on the uterine epithelium compared to continuous administration. Our results strengthen data of clinical studies demonstrating a good endometrial safety of pulsed estrogen therapy

Estrogen promotes microvascular pathology in female stroke-prone spontaneously hypertensive rats (SHRSP)

Estrogen produces both beneficial and adverse effects on cardiovascular health via mechanisms that remain unclear. Female SHRSP maintainedon a high-salt intake rapidly develop stroke and malignant nephrosclerosis. To determine whether estrogen contributes to stroke-related mortality in this model, we examined the effect of ovariectomy with or without estradiol benzoate (E2) therapy and antiestrogen treatment with tamoxifen. SHRSP were ovariectomized (Ovex) or sham operated (Sham) at 4 weeks of age and then dosed chronically with E2 at 10 μg/Kg 3 times a week or vehicle (VEH) starting at 5 weeks of age. All SHRSP received 1% NaCl drinking solution starting at 8 weeks of age. Ovex rats lived significantly (P<0.01) longer (15.1±0.3 weeks, n=4) than Sham (13.6±0.2 weeks, n=6) or Ovex & E2 (12.4±0.2 weeks, n=7). In a second survival study, six saline-drinking female SHRSP with intact ovaries received 2.3 mg/Kg of tamoxifen 3 times a week and six non-ovariectomized littermates received VEH. Tamoxifen treatment delayed the onset of stroke-related mortality by at least two weeks (P<0.01) but did not prevent the development of severe hypertension. Ovex (n=13), Sham (n=14), and Ovex & E2 (n=9) SHRSP that were sacrificed at 11.5 weeks of age were also studied so that renal microvascular injury could be assessed in groups that were matched for age. Systolic blood pressure (SBP) prior to death was lower in Ovex compared with Sham and Ovex & E2 but did not differ between Sham and Ovex & E2 (Table). Ovex & E2had elevated blood urea nitrogen (BUN), proteinuria and renal lesions of thrombotic microangiopathy (TMA) compared with either Sham or Ovex. Ovex & E2 developed worse pathology than Sham, perhaps due to the absence of vascular protective factors from the ovary. Consistent with the ability of Ovex to diminish endogenous estrogen levels, uterine dry weight (mg) was significantly less in Ovex (8±1) compared to Sham (76±4) and Ovex & E2 (59±3). The results of these studies suggest that estrogen plays a role in promoting stroke and renal microvascular injury in saline-drinking female SHRSP. Values are mean ± SEM; P<0.01 vs Ovex; #P<0.01 vs Sham Values are mean ± SEM; P<0.01 vs Ovex; #P<0.01 vs Sham

Effects of relaxin administration in early gestation or prior to mating on uterine length and fetal survival in gilts.

The objective of this research was to determine the effect of administration of porcine relaxin to gilts during early gestation, or during the follicular phase of the estrous cycle immediately preceding mating, on the length of the uterus and consequently the number of surviving fetuses. Experiment 1 determined the individual and combined effects of 10 days of administration of relaxin (0.5 mg, 4 times daily), estradiol benzoate (1 mg, 2 times daily), and progesterone (50 mg, 2 times daily) on uterine wet weight and length in 58 ovariectomized 8-mo-old pubertal gilts. Relaxin alone had no effect on either uterine length or wet weight. Estrogen increased uterine wet weight, and this effect was augmented by relaxin. Progesterone increased uterine length, and this effect was augmented by estrogen. Combined treatment with progesterone, estrogen, and relaxin increased both uterine length and wet weight maximally. Experiment 2 determined the effects of relaxin administration in early gestation or prior to mating on uterine length and fetal survival in 75 unilaterally ovariectomized-hysterectomized gilts. Relaxin (0.5 mg, 4 times daily) was administered during three treatment periods, and uteri were collected on Day 40 of gestation. In this study, relaxin administration from Days 11 to 20 of gestation reduced the number of live fetuses (p = 0.01) and percentage survival (p = 0.01) and resulted in shorter uterine length (p = 0.01) and lower uterine wet weight (p = 0.03) than in controls, but did not affect length of uterus or uterine dry weight. Relaxin administration from Days 22 to 31 of gestation did not influence fetal survival, uterine length, uterine length per fetus, uterine wet weight, or uterine dry weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of ovarian steroids on relaxin-induced uterine growth in ovariectomized gilts

This study examined the influence of ovarian steroids on the uterotropic actions of relaxin (RLX) in ovariectomized prepubertal gilts. Ovariectomized gilts received (im) corn oil (CO), estradiol benzoate (EB), or EB and progesterone (P) for 0-16 days. Steroid administration was patterned to approximate the plasma concentrations of endogenous ovarian steroids observed during 1) the follicular phase (EB), 2) luteal phase (EB+P), and 3) early pregnancy (EB+P+EB). Half of each group also received PBS or 0.5 mg RLX every 6 h for 54 h, coinciding with the final 2 days of the experimental period. After hysterectomy, uterine tissues were analyzed for water, dry matter, protein, DNA, glycosaminoglycans (GAGs), and collagen contents. Administration of EB or P increased uterine weight 5- to 6-fold, but no differences were observed between EB+P- and EB+P+EB-treated gilts. Cotreatment with RLX enhanced steroid-induced uterine growth 40-70%, and RLX stimulated growth in CO- and EB+CO control gilts 2- to 3-fold. The water content of uterine tissues was greater in EB-, EB+P-, and EB+P+EB-treated gilts than in their respective controls, and this response was augmented by RLX in all treatment groups. Administration of steroids stimulated a 4- to 5-fold increase in uterine dry weight compared to that in controls, with responses not differing between EB+P- and EB+P+EB-treated gilts. In all groups, RLX increased uterine dry weight. Protein and DNA contents of uterine tissue increased with steroid treatment, but neither variable differed between EB+P- and EB+P+EB-treated gilts. Administration of RLX, alone or in combination with steroids, increased protein and DNA contents of uterine tissues. The tissue content of GAGs increased in response to steroids, and coadministration of RLX did not alter this response. Although the uterine tissue concentration of collagen was reduced in steroid- and RLX-treated gilts, the collagen content of the uterus was not affected by the various treatments. The results of this study indicate that RLX is a potent stimulator of uterine growth under a variety of steroidal environments. RLX- or steroid-induced uterine growth was manifest by increased water, dry matter, protein, and DNA and GAG contents, but the uterine content of collagen was not affected. The overall growth-promoting effects of EB and the stimulation of DNA accretion by RLX were not observed when gilts were cotreated with P.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of ovarian steroids on relaxin-induced uterine growth in ovariectomized gilts.

This study examined the influence of ovarian steroids on the uterotropic actions of relaxin (RLX) in ovariectomized prepubertal gilts. Ovariectomized gilts received (im) corn oil (CO), estradiol benzoate (EB), or EB and progesterone (P) for 0-16 days. Steroid administration was patterned to approximate the plasma concentrations of endogenous ovarian steroids observed during 1) the follicular phase (EB), 2) luteal phase (EB+P), and 3) early pregnancy (EB+P+EB). Half of each group also received PBS or 0.5 mg RLX every 6 h for 54 h, coinciding with the final 2 days of the experimental period. After hysterectomy, uterine tissues were analyzed for water, dry matter, protein, DNA, glycosaminoglycans (GAGs), and collagen contents. Administration of EB or P increased uterine weight 5- to 6-fold, but no differences were observed between EB+P- and EB+P+EB-treated gilts. Cotreatment with RLX enhanced steroid-induced uterine growth 40-70%, and RLX stimulated growth in CO- and EB+CO control gilts 2- to 3-fold. The water content of uterine tissues was greater in EB-, EB+P-, and EB+P+EB-treated gilts than in their respective controls, and this response was augmented by RLX in all treatment groups. Administration of steroids stimulated a 4- to 5-fold increase in uterine dry weight compared to that in controls, with responses not differing between EB+P- and EB+P+EB-treated gilts. In all groups, RLX increased uterine dry weight. Protein and DNA contents of uterine tissue increased with steroid treatment, but neither variable differed between EB+P- and EB+P+EB-treated gilts. Administration of RLX, alone or in combination with steroids, increased protein and DNA contents of uterine tissues. The tissue content of GAGs increased in response to steroids, and coadministration of RLX did not alter this response. Although the uterine tissue concentration of collagen was reduced in steroid- and RLX-treated gilts, the collagen content of the uterus was not affected by the various treatments. The results of this study indicate that RLX is a potent stimulator of uterine growth under a variety of steroidal environments. RLX- or steroid-induced uterine growth was manifest by increased water, dry matter, protein, and DNA and GAG contents, but the uterine content of collagen was not affected. The overall growth-promoting effects of EB and the stimulation of DNA accretion by RLX were not observed when gilts were cotreated with P.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of purified porcine relaxin on the uterus of gilts during early pregnancy

Twenty-three gilts were assigned io receive a 1.0 mi injection of either saline (C) or 0.5 mg purified porcine relaxin in saline (pRLX) every 6 h on Days 6–11 of gestation. All 12 gilts assigned to relaxin treatment were pregnant on Day 11. Following hysterectomy on Day 11, mean uterine wet weight was greater ( P < 0.05) in pRLX-trcated gilts (1247.6 ± 94.0 g) as compared with control animals (958.5 ± 98.2 g). Mean uterine dry weight was 123.7 ± 6.6 g and 111.8 ± 8.9 g ( P > 0.10) in pRLX and C gilts, respectively. Uterine volumes and circumferences were also increased ( P < 0.05 and P < 0.01, respectively) by pRLX treatment, but no difference was observed between treatments in uterine length or total uterine DNA and protein content. Relaxin treatment resulted in mean plasma relaxin concentrations of 4.08 ± 0.27 ng ml −1. Mean plasma concentrations of progesterone and PGFM (15-keto-13, 14-dihydro PGF 2α) were not affected by exogenous relaxin. In conclusion, exogenous relaxin increased uterine size during early pregnancy in gilts. The observed uterotropic effects of relaxin appear to be primarily due to cellular hypertrophy as a result of water imbibition.

Uterine Insulin-Like Growth Factor-1: Regulation of Expression and Its Role in Estrogen-Induced Uterine Proliferation*

THE response of the uterus to estrogen is a complexphenomenon involving numerous biochemical events (1). The most dramatic outcome of estrogenization of the immature uterus is the proliferation of various cell types. It is customary to divide the response of the uterus to estrogen into two major temporal phases. In the early phase, within the first 4 h after estrogen administration, there is an increase in uterine wet weight (2), glucose metabolism (3), histamine depletion (4), and RNA polymerase activity (5). One of the early events that is likely to be important in the proliferative response of the uterus to estrogen is activation of protooncogenes which encode nuclear regulatory proteins (6–8) and the enhanced expression of growth factors and their receptors (9) and cAMP-independent protein kinase (10). The intermediate and late phase (4–48 h after estrogen) responses include increases in protein and RNA synthesis and an increase in uterine dry weight and DNA content (11, 12).

Uterotropic Actions of Relaxin in Prepubertal Gilts1

Uterotropic actions of relaxin (RLX) have been demonstrated in rats and mice but not in other species. Experiments were conducted to assess (1) if RLX has uterotropic effects in prepubertal gilts and (2) if RLX-induced imbibition of water by uterine tissues is mediated by histamine. Prepubertal gilts received (i.m.) either 0.5 mg pRLX (greater than or equal to 3000 U/mg; n = 10) in 0.1 M phosphate-buffered saline (PBS) or PBS vehicle (n = 8) every 6 h for 54 h. Additionally, one-half of each group received either (1) the histamine receptor antagonists (300 mg i.m. of each), pyrilamine maleate (H1) and cimetidine (H2), in PBS and corn oil, respectively, or (2) control vehicles every 6 h for 66 h beginning 12 h prior to initiation of RLX treatment. Treatment with RLX stimulated a twofold increase (p less than or equal to 0.05) in uterine weight in prepubertal gilts. Increases in total uterine weight were manifested by greater (p less than or equal to 0.05) uterine water content and dry weight in RLX-treated gilts. Cotreatment with histamine receptor antagonists did not alter RLX-induced changes in uterine water content or dry weight. Uterine contents of soluble protein and DNA were greater (p less than or equal to 0.05) in RLX-treated gilts compared to controls. Treatment with RLX tended (p approximately 0.08) to reduce protein; DNA ratio of uterine tissues and increased (p less than or equal to 0.05) uterine DNA as a percentage of uterine dry weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of the mouse uterus to nafoxidine stimulation: agonism and antagonism.

Nafoxidine (NAF) acts as an estrogen agonist or antagonist depending on the animal model used. In the CD-1 mouse uterus, a three-day uterine bioassay of NAF produced a bell-shaped dose response curve with a maximal uterine wet weight increase at 200 micrograms/kg; this dose produced only a fractional increase in uterine dry weight. Combination treatment with NAF and estradiol antagonized estradiol stimulation of both wet and dry weight parameters. The time course of uterine wet weight stimulation following a single injection of NAF had an early pattern (0-10 h) similar to that of estradiol. However, at later times after stimulation, the patterns changed dramatically: the low NAF dose (200 micrograms/kg) returned to control levels by 24 h; estradiol and the high dose NAF (1.7 mg/kg) showed sustained stimulation, which peaked at 36 h with NAF compared to 24 h for estradiol. Nuclear estrogen receptor (ER) levels were measured after a single injection of 1.7 mg/kg NAF and showed a bimodal pattern similar to that seen with estradiol, with increases at 1 h and 8 h, although the overall ER levels were elevated above those seen with estradiol. Cytosolic ER levels with NAF decreased by 1 h and remained low up to 48 h. NAF treatment did stimulate uterine DNA and RNA synthesis, with a delayed time course compared to estradiol. DNA synthesis following a single 1.7 mg/kg dose of NAF was 2.5 times higher than that produced by 20 micrograms/kg estradiol. NAF treatment resulted in hypertrophy and hyperplasia in the luminal epithelium but not in the glandular epithelium. Long-term exposure to estradiol for 5 wk resulted in development of uterine cystic glandular hyperplasia and increased secretory activity; long-term exposure to NAF produced a more significant tissue hyperplasia but no secretions. These studies show that NAF stimulates some of the receptor-mediated responses attributed to an estrogen agonist in the mouse uterus; but, when co-administered with estradiol, NAF antagonizes some aspects of estrogen action.

Pulsatile administration of gonadotropin-releasing hormone agonist to gilts actively immunized against gonadotropin-releasing hormone.

Sexually mature gilts (n = 20) were actively immunized against GnRH. Primary and booster immunizations of GnRH conjugated to bovine serum albumin induced production of antibodies in all gilts. Nineteen of the gilts became acyclic with suppressed concentrations of gonadotropins and estradiol. Intravenous challenges with 100 micrograms GnRH and 5 micrograms D-(Ala6, des-Gly-NH2(10)) ethylamide GnRH (a GnRH agonist that did not cross-react with antibodies produced by the gilts) caused release of LH and FSH, indicating maintenance of secretory capacity of pituitary gonadotropes in the immunized animals. Gilts were given 100 ng GnRH agonist at 2-h intervals for 72 h (n = 4) or 144 h (n = 10) or did not receive agonist (n = 5). Blood samples were taken every 6 h, and detectable concentrations of LH were observed in 42% and 52% of samples taken from gilts treated with or without agonist. In contrast, serum concentrations of FSH and estradiol were undetectable. Reproductive tracts and anterior pituitaries were taken from gilts at the conclusion of pulsatile administration of GnRH agonist or at 144 h for controls. Pituitary concentration of LH and FSH, uterine wet and dry weight, and size of the uterus were similar among groups. Paired ovarian weights for treated gilts pulsed with GnRH agonist for 72 h were heavier (P less than .05); however, ovaries from all immunized gilts were atrophied without follicular structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamics of estrogen induction of glandular kallikrein in the rat anterior pituitary

Glandular kallikrein has recently been identified as an estrogen-induced protein of the rat anterior pituitary. This study examined the dynamics of the estrogen induction of anterior pituitary glandular kallikrein in the ovariectomized rat. The estrogen induction of uterine dry weight was also examined for purposed of comparison. 17β-Estradiol (0.1–100 μg/day) produced dose-dependent increases in anterior pituitary glandular kallikrein, with the highest dose producing a 60-fold increase. Time-course studies demonstrated that a lag phase of 2–3 days was required before these estrogen effects on glandular kallikrein became evident, and levels were still rising between 7 and 10 days of treatment. The dynamics of the estrogen induction of glandular kallikrein resembled the estrogen induction of uterine dry weight with regard to estrogen sensitivity and the presence of a lag phase before estrogen-induced increases. However, uterine dry weight responde more rapidly to estrogen than did anterior pituitary glandular kallikrein, and reached a plateau after 5 days of estrogen treatment.

Induction of progesterone receptor by androgens in the mouse uterus

The comparative abilities of 3 naturally occurring androgens to compete for [ 3H]estradiol-17β ([ 3H]E 2)-binding sites in uterine cytosol and to induce uterotrophic responses in immature female mice have been investigated. 5α-Androstane-3β,17β-diol (3β-diol), 5α-androstane-3α,17β-diol (3α-diol) and 5-androstene-3β,17β-diol (Δ5-diol) are all effective at diminishing cytoplasmic [ 3H]E 2 binding. Their relative effectiveness are in the order of 3β-diol > Δ5-diol = 3α-diol. When these steroids were injected intramuscularly (two 100–200 μg injections) into immature female mice (21 days old), they induced similar elevations of uterine dry weight, water content, cytosolic estrogen (ER) and progesterone (PR) receptor contents, and nuclear ER content as did estradiol-17β (E 2). 3β-Diol was the most effective steroid at inducing cytosolic and nuclear ER, and PR production in mouse uterus. Followed in effectiveness was Δ5-diol and 3α-diol. Unexpectedly, 3β-diol was found to be more potent than E 2 in stimulating uterine ER and PR increases. Nonetheless, the androgens are poorer stimulators of uterine dry weight increase and water retention than E 2 is. These results indicate that the androgens may interact with the ER system in the uterus to bring about the uterotrophic responses and 3β-diol is a more estrogenic steroid than Δ5-diol and 3α-diol in the mouse uterus.

Estrogen effects on NADH oxidase and superoxide dismutase in prepubertal female rats

Thirty-four day old, ovariectomised rats were treated with increasing doses of estradiol, 2-hydroxyestradiol 2,3-dimethyl ether (23E 2), 4-hydroxyestradiol 3,4-dimethyl ether (34E 2) and 4-methoxy-estradiol (4ME 2) for five days by subcutaneous injection. Superoxide dismutase, phenol activated NADH oxidase and uterine dry weights were determined. Only estradiol was found to be uterotrophic and increased NADH oxidase activity in these experiments. Both 23E 2 and 34E 2 treatment reduced the enzyme activity significantly. Though 4ME 2 showed a decrease in NADH oxidase at 0.05μg/100gm body weight there was no further decrease at higher dose (5μg/100gm). The Superoxide dismutase (SOD) in uterus and liver was unaffected by estradiol, while 23E 2, 34E 2, and 4ME 2 significantly reduced SOD in both liver and uterus. These results indicate that 23E 2, 34E 2 and 4ME 2, in spite of their non-uterotrophic property, affect uterine metabolism. Furthermore, in view of the reports indicating the importance of SOD levels in various tumors and since catecholestrogens are observed to reduce SOD levels in liver and uterus, it is suggestive that catecholestrogens may play an important role in the pathophysiology of certain tumors.

Uterine growth and differentiation in response to ovarian steroids in the hamster.

Uterine response to progesterone and estradiol was examined in spayed hamsters and compared with that in intact hamsters. Estradiol was uterotropic whereas progesterone was relatively less so. The greatest increase in uterine dry weight was observed when the 2 hormones were given simultaneously. Stromal edema and mitoses were evident whenever progesterone was included in the hormonal regimen. Luminal closure was also observed under these conditions and was especially pronounced when estradiol was given as well and uterine morphology was similar to that observed during pregnancy. In the hamster receiving estradiol alone, the glands were abundant and epithelial mitoses were also observed but luminal closure did not occur. This condition resembled the uterine appearance at proestrus. The incorporation of [3H]-leucine in uterine luminal proteins was 40-fold greater when estradiol was injected compared with the values obtained after progesterone was given; progesterone given with estradiol dampened the incorporation nearer the level obtained with progesterone alone. The incorporation was also substantially greater during proestrus compared with the levels during pregnancy. Two groups of labeled proteins with mol ∼5.5 × 104 and 10 × 104 were detected during proestrus. However, only the former was prominent whenever progesterone was included in the hormonal regimen and during pregnancy and only the latter was detected in females receiving estradiol alone. In comparison with the condition in the rat, estradiol was substantially less uterotropic in the hamster and progesterone also potentiated rather than antagonized the uterine growth response to estradiol. The difference in the uterine response to estradiol may explain why the blastocyst cannot enter into diapause in the hamster under endocrine conditions similar to those in the rat.

Estrogen‐receptor binding: Relationship to estrogen‐induced responses

The relationship between nuclear binding of the receptor-estrogen complex (R-E) and estrogenic responses was examined. Nuclear-bound R-E was measured by the [3H] estradiol exchange assay, which permits the quantification of R-E as a function of either endogenous or non labeled estrogen. The quantity of nuclear R-E fluctuated as a function of blood levels of estrogen during the estrous cycle in the rat. This indicates that the accumulation of the R-E complex by the nucleus of uterine cells may be of physiologic significance and under the control of endogenous estrogen.