Secretion of unconjugated estrone during pregnancy and around parturition in goats

The secretion of unconjugated estrone and its production site in pregnant goats were investigated in vivo. The mean estrone concentration (n = 15) in the peripheral plasma increased gradually, being 83 pg/ml on Day 40 and 483 pg/ml on Day 140 after mating. The estrone concentration increased rapidly after Day 2 before partum, reaching a peak at parturition (2370 pg/ml), and falling to 171 pg/ml at Day 1 post partum. The concentrations of estrone from the umbilical vein and umbilical artery did not differ from that found in the maternal jugular vein, suggesting that the fetus does not take part in estrogen production. The estrone concentration from the uterine vein after the fetus was removed was higher than the concentrations found in the maternal jugular vein and umbilical artery. In the placental tissue, a high concentration of estrone (18157 pg per gram of wet tissue) was detected. These findings suggest that the main production site of unconjugated estrone is the placenta.     

The endogenous concentration of estradiol and estrone in pathological human postmenopausal endometrium

The endogenous estrone (E1) and estradiol (E2) levels (in pg/g tissue) were measured in 7 postmenopausal patients with a hyperplastic endometrium, in 3 with an atypical adenomatous hyperplastic endometrium and in 13 with a carcinomatous endometrium. These tissue concentrations were compared with the E1 and E2 concentrations in plasma (pg/ml) and with data from a control group of postmenopausal women with atrophic endometria. The tissue levels of both steroids showed large variations and there were no significant correlations with their plasma levels. In the hyperplastic and the atypical adenomatous hyperplastic group the mean E2 tissue level was higher compared with the mean E1 tissue level, despite the excess of E1 over E2 in peripheral plasma. In the carcinomatous group the mean E1 tissue level was higher, although not significantly, than the mean E2 tissue level. There were no significant differences between the E1 and E2 tissue levels in the three different pathological groups as compared to the atrophic control group. We conclude that it is unlikely that estrogens alone play a crucial role in the development of a pathological endometrium.     

Changes in plasma levels of estrone sulfate and estrone in the pregnant ewe around parturition

A method for the extraction, separation and measurement of estrone sulfate and estrone in a single plasma sample is described. The method has been applied to the determination of plasma levels of estrone sulfate and estrone in pregnant ewes over the period 60 hr before to 20 hr after parturition. The study revealed that the plasma levels of estrone sulfate and estrone began to increase about 40 hr before parturition, reached a peak at parturition and then declined rapidly to levels below the sensitivity of the method by 15 hr postpartum. The peak level of estrone sulfate recorded at parturition was 103 pmol (38 ng) per ml of plasma which was approximately 30 times greater than the corresponding peak level of estrone.     

Formation of estrone and estradiol from estrone sulfate by normal breast parenchymal tissue

The study was designed to determine the process and limitations by which estrone sulfate may be a precursor of estradiol in the parenchymal cells of the normal breast. The concentration of estrone sulfate in breast nipple aspirate fluid was 1000-fold greater than that of estradiol. Concentrations of 3H-estrone sulfate in parenchymal cells were only 0.20-0.33 times that of the 1.0 nM concentration in the medium, while 3H-estrone achieved concentrations up to 24 times that in the medium at 37 degrees C. Nevertheless, estrone sulfate added to the medium was linearly converted within a 1000-fold concentration range to estrone in intact cells with a mean half-time of conversion of 628 min per 10(6) cells. Homogenized cells had a half-time of 246 min per 10(6) cells. Thus, the time for entry of estrone sulfate into cells reduced the rate by approximately 55%. In split samples, the Vmax values (+/- S.D.) for intact and homogenized cells were 12.6 +/- 1.4 and 18.3 nmol/h mg DNA, respectively (P<0.03). The corresponding Km values for intact and homogenized cells were 6.0 +/- 1.1 and 4.7 +/- 1.0 microM. Conversion of estrone sulfate to estradiol was more efficient in intact cells than in homogenates with mean half-times of 2173 and 7485 min per 10(6) cells, respectively. Conversion of estrone to estrone sulfate did not occur in these cells despite sulfonation of estrone by MCF-7 breast cancer cells under identical conditions. It is concluded that estrone sulfate can serve as a precursor for estradiol in normal breast tissue. Conversion of estrone to estradiol is a limiting step in the process.     

Metabolism of (4-14C)estrone by sheep erythrocytes around the time of parturition.

The metabolism of [4-14C]estrone in vitro by red blood cells of sheep in late pregnancy and after partuirition has been studied. [14C]estrone (600 ng) was incubated with 0.5 ml erythrocytes plus 0.5 ml of Krebs-Ringer phosphate buffer, pH 7.4, for 2 h at 37 degrees C in an atmosphere of air. After incubation, [3H]estrogens were added to the incubation medium as internal standards for identification and for correction for procedural losses. Metabolites were isolated and purified by chromatography, acetate derivative formation, and recrystallization to a constant 3H/14C ratio. Approximately 20% and 2% of added estrone were converted to 17beta-estradiol and 17 alpha-estradiol, respectively. The remainder was recovered unchanged. Daily measurements of 17 beta-hydroxysteroid dehydrogenase activity in erythrocytes of five ewes, over the period 8 days prepartum to 4 days postpartum, showed no significant change in activity.     

The relationship between fetal breathing movements and prostaglandin E2 during ACTH-induced labour in sheep

We measured fetal breathing movements and fetal carotid arterial prostaglandin E concentrations during adrenocorticotrophin-induced labour in 6 pregnant sheep and in 6 control animals starting at day 127. The 6 ACTH-treated animals went into labour on average 97 h after the onset of infusion and the incidence of fetal breathing movements diminished during the last 12h before the onset of labour. There was a significant negative relationship between the incidence of fetal breathing movements and fetal carotid arterial prostaglandin E concentrations (r = -0.88; P less than 0.001) in ACTH treated animals. These data suggest a role for prostaglandin E in the diminution of fetal breathing movements prior to the onset of labour.     

Studies on spirolactone steroid antagonists in ACTH-induced hypertension in sheep

This study investigated the anti-mineralocorticoid potency and haemodynamic effects of a series of mineralocorticoid antagonists of the spirolactone type (RU 28318, spironolactone, K-prorenoate, K-canrenoate and canrenone), for their ability to prevent the development of ACTH-induced hypertension in conscious sheep. In vivo bioassay, using aldosterone dependent changes in parotid salivary [Na+]/[K+] of sodium depleted adrenalectomized sheep, showed spironolactone was the most potent anti-mineralocorticoid tested. Infusions of the antagonists at equal doses alone for 4 days demonstrated that none affected mean arterial pressure, except for K-prorenoate which exhibited slight pressor activity. All the antagonists produced a natriuresis. Some of the steroid antagonists of the spirolactone group blocked the development of ACTH hypertension in sheep, spironolactone being the most effective. This study provides additional evidence for an essential mineralocorticoid component in ACTH-induced hypertension.     

Dexamethasone and estradiol benzoate induced parturition in dairy cattle

Fifteen 2-year-old Holstein cows and 21 mature Holstein cows were assigned to one of three groups. Cows in Group I calved spontaneously. Cows in Groups II and III received single intramuscular injections of 20 mg dexamethasone and 25 mg estradiol benzoate to induce parturition prematurely. In addition, cows in Group III received a single intramuscular injection of 12.5 mg estradiol benzoate 48 hr prior to dexamethasone and estradiol benzoate. The objective of the experiment was to determine the effectiveness of estradiol benzoate in combination with dexamethasone on traits at parturition and on productive and reproductive characteristics following parturition. Induction of parturition shortened gestation length and increased the incidence of retained placentas (both P < .01). All induced cows calved between 21 and 59 hr postinjection with less (P < .05) udder edema when compared to control cows. Mean plasma estrogen concentrations, using an assay system which does not measure estradiol benzoate, were not different among groups following injections of estradiol benzoate. Mean estradiol-17β concentrations in induced cows, however, using an assay system which does recognize estradiol benzoate (70.8% crossreactivity), were higher (P < .01) following estradiol benzoate injection, tended to be higher through parturition, and remained elevated (P < .01) at 12 and 24 hr following parturition when compared to cows calving spontaneously. Mean monthly milk production and the 2x, 305-ME records for milk, fat and FCM were not different among groups.     

Changes in estrone and estradiol synthesis in fetal and newborn rats

The question was approached whether estradiol synthesis by the rat ovary gained in importance with age relatively to estrone synthesis, which predominated largely in the 20-day-old fetus. Three stages were investigated, i.e. fetal stage 21 days and stages 2 and 7 days after birth. Ovaries were cultured in vitro in the presence of various radioactive androgens, and the conversion percentages into estrone (E1) and estradiol (E2) were determined by double isotopic dilution combined with recrystallization to constant specific activity. Insignificant in the 21-day-old fetus (E1/E2 ratio = 40), estradiol synthesis increased relatively to estrone synthesis in the 2-day-old neonate and still more at the stage of 7 days (E1/E2 ratio = 3). FSH had no effect on estrogen synthesis at the 3 stages investigated.     

Metabolism of estrone sulfate in the pregnant sheep

The metabolism of ³H-estrone sulfate (³H-E₁S) in 4 pregnant sheep, two injected i.v. and two i.m., has been studied. Intravenously injected ³H-E₁S had a plasma half-life of approximately 8 min, and metabolic clearance rate of approximately 800 ml/min. Using this clearance rate and the previously published mean plasma concentration of E₁S, the estimated production rate of E₁S is between 8.8 nmol (3.3 μg) and 78.2 nmol (29.1 μg) per min from 2-day to 0-day before parturition.Intramuscularly injected ³H-E₁S disappeared from plasma linearly and was completely cleared well within 3 hours. In all cases, whether i.v. or i.m. injected, the main metabolite isolated was ³H-estradiol-17β-3-sulfate, with only a trace amount as ³H-estradiol-17β-3-sulfate.     

Influence of environmental disturbances on uterine motility during pregnancy and parturition in rabbit and sheep

The effect of stressful stimuli on uterine motility during pregnancy and parturition was studied in sheep and rabbits. The effects of epinephrine and various alpha- and beta- adrenergic blocking agents were also investigated. By comparing the results of these experiments, the authors conclude that the increase in epinephrine level (stress response of the organism) is the direct cause of the observed changes in uterine motility.Both stress and epinephrine caused either an activation or an inhibition of uterine motility. The direction of the effect depended on the ratio of sex-steroid concentrations in the plasma. Blood plasma levels of oestradiol-17β and of progesterone were determined in the sheep. Both stress and epinephrine inhibited uterine motility only when plasma levels of oestradiol-17β were very high (oestrogen-domination). The biological relevance and clinical implications are discussed.