Comparison of serum oestrogen concentrations in post-menopausal women taking oestrone sulphate and oestradiol.

Mean serum concentrations of oestradiol-17beta, oestrone, and oestrone sulphate in postmenopausal women were the same when measured up to six hours after treatment with either piperazine oestrone sulphate 1.5 mg or oestradiol valerate 2 mg. Maximum concentrations of oestradiol were less than those of oestrone, but oestrone sulphate reached concentrations about 30 times higher than those of oestrone. The rapid conversion of oestradiol valerate to oestrone and oestrone sulphate does not support the suggestion that in menopausal women oestradiol is less likely to be associated with a risk of endometrial carcinoma than oestrone sulphate, since the two preparations appear to become identical after ingestion.     

Steroid hormones in uterine washings and in plasma of gilts between days 9 and 15 after oestrus and between days 9 and 15 after coitus

Between Days 9 and 15 after oestrus, concentrations of pregnenolone, pregnenolone sulphate, dehydroepiandrosterone (DHEA), DHEA sulphate, androstenedione, oestrone and oestrone sulphate in free uterine fluid collected from non-pregnant gilts were greater than respective values in plasma (P less than 0.05). The total contents of pregnenolone, progesterone, DHEA, testosterone, oestrone and oestradiol in washings from pregnant uteri exceeded (P less than 0.05) respective non-pregnancy levels during this same period. Concentrations of pregnenolone, pregnenolone sulphate, DHEA, DHEA sulphate, androstenedione, oestrone, oestrone sulphate and oestradiol in free uterine fluid recovered from gravid uteri were also higher (P less than 0.05) than respective plasma values. By contrast, the progesterone concentration in uterine fluid from pregnant animals was lower (P less than 0.001) than the plasma value. Concentrations of DHEA, DHEA sulphate, androstenedione and oestrone sulphate in plasma of pregnant gilts between Days 9 and 15 after mating exceeded (P less than 0.05) the respective concentrations in unmated gilts between Days 9 and 15 after oestrus. Plasma levels of pregnenolone sulphate were lower (P less than 0.05) in the pregnant animals. We therefore suggest that the endometrium of the pig can concentrate steroid hormones in uterine fluid and that increases in steroid levels in this milieu between Days 9 and 15 after coitus reflect steroidogenesis by embryonic tissues and modification of enzyme activities within uterine tissues under the influence of progestagens. The pool of steroid sulphoconjugates present in uterine fluid between Days 9 and 15 post coitum could serve as an important precursor source for progestagen, androgen and oestrogen synthesis by tissues of pig embryos before implantation.     

The effects of androgens and cortisol on the in vivo metabolism of oestradiol

We have examined the effect of co-administration of dehydroepiandrosterone sulphate, 5-androstenediol or cortisol on the metabolic clearance rate of oestradiol (MCR-E2) and conversion of oestradiol to oestrone (CRE2E1). Previous studies have shown that these androgens influence the metabolism of oestradiol in vitro while cortisol alters the distribution of oestradiol in plasma. The MCR-E2 and CRE2E1 were measured after 2.5 and 5 h of [3H]oestradiol infusion with co-infusion of androgen or cortisol starting after 2.5 h of tracer infusion. For one subject who did not receive co-infusion of another steroid no significant change in MCR-E2 or CRE2E1 occurred over the 5-h period. For other subjects, however, the MCR-E2 decreased by 18 +/- 7% (mean +/- SD) while the CRE2E1 increased by 45 +/- 12%. It is possible that these results are due to: changes in the distribution of oestradiol in plasma; differences in the metabolism of oestradiol bound to albumin or SHBG, or an effect of androgens or cortisol on the uptake of [3H]oestradiol by the liver.     

Changes in oestrogen-synthesizing ability of preovulatory bovine follicles relative to the peak of LH

Preovulatory bovine follicles (n = 28) were collected at different times after the onset of standing oestrus until shortly before ovulation. In-vitro conversion of tritiated androstenedione in the presence of NADPH by homogenates of the follicular wall was compared in phases relative to the LH peak. During phase 0 (before the LH surge) conversion into oestradiol-17 beta was high and production of oestrone was about 8-fold lower. During phases 1 (0-6 h after the LH peak) and 2A (6-14 h after the LH peak) the production of oestradiol and oestrone remained constant; the percentage of remaining androstenedione increased. In phase 2B (14-20 h after the LH peak) conversion into oestradiol and oestrone had decreased to about one third correlating with a higher percentage of remaining androstenedione. In phase 3 (20 h after the LH peak until ovulation) conversion into oestradiol and oestrone remained constant. The ratio between the production of oestrone and oestradiol remained constant throughout the phases of preovulatory development (0.13), indicating a concurrent inhibition of aromatase and 17 beta-hydroxysteroid dehydrogenase activities. Conversion into 19-hydroxyandrostenedione showed a pattern similar to that of oestradiol, and testosterone was produced in minute quantities. The results indicate that in preovulatory bovine follicles eventual inhibition of aromatization takes place at about 14 h after the preovulatory LH peak.     

Effect of vasoactive intestinal polypeptide (VIP) on steroidogenesis in women

The VIPergic nervous system appears to be the major peptide-containing neuronal component in the female genital tract. Evidence has been put forward that exogenous VIP is able to stimulate progesterone secretion. In the present study the effect of human VIP (900 pmol/kg body weight per h i.v. during 30 min) on steroidogenesis in six female volunteers was investigated. The experiments were performed between the 6th and 14th day of their menstrual cycle, and peripheral venous blood was collected before, during and after infusion of VIP. The concentrations of VIP, oestradiol, progesterone, testosterone, androstenedione (AD), dihydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHAS), sex hormone binding globulin (SHBG) and cortisol were measured. The infusion of VIP was accompanied by a 15% increase (P less than 0.05) in serum oestradiol concentrations, from a mean basal concentration of 0.58 nmol/l. The concentrations of testosterone and DHT also increased significantly. No effect of VIP on progesterone, AD, DHAS, SHBG or cortisol was observed. In the light of the presence of VIP in nerve fibres of the steroid producing tissue, this stimulatory effect of VIP might reflect a direct action on the ovary or the adrenal gland.     

Hormonal profiles after the menopause.

The endocrinological changes of the climacteric have been defined by studying the concentrations of follicle-stimulating hormone (FSH), luteinising hormone (LH), androstenedione, testosterone, oestrone, and oestradiol in 60 normal postmenopausal women of different menopausal ages. The women were studied in six groups, according to the number of years since their menopause. One year after the menopause androstenedione, oestrone, and oestradiol concentrations were reduced to about 20% of the values recorded during the early proliferative phase of the menstrual cycle. At the same time the mean concentration of FSH had risen by a factor of 13-4 and that of LH by a factor of 3-0. Concentrations of both gonadotrophins reached a peak of 18-4 and 3-4 times the proliferative phase value respectively after two to three years, and then gradually declined in the next three decades to values that were 40-50% of these maximal levels. Testosterone concentrations remained mostly in the normal range for premenopausal women but were depressed to 60% of these levels two to five years after the menopause, and the mean androstenedione levels showed a significant increase in the same group of women. The concentrations of both oestrone and oestradiol remained consistently low for 10 years after the menopause, but oestradiol concentrations inexplicably increased in the last two decades, with levels at the lower end of normal range for reproductive women in six patients.     

Metabolism of [3H]oestradiol in vivo by normal breast and tumour tissue in postmenopausal women

Tumour and normal breast tissue was obtained from postmenopausal breast cancer patients following [3H]oestradiol infusion (50 mu Ci over a 12 h period). The fraction of radioactivity present as oestradiol or oestrone was measured and the results expressed both as the ratio of oestradiol-oestrone and as the percentage oestrogen present as oestrone, and the findings compared with in vitro measurements of 17 beta-hydroxysteroid dehydrogenase activity. Concentrations of 5-androstene-3 beta, 17 beta-diol, dehydroepiandrosterone and its sulphate and testosterone were measured and related to oestradiol metabolism. The study demonstrated that tumour tissue is less able to metabolise oestradiol to oestrone than is normal breast tissue and indicated that the ability of the tissue to detoxify oestradiol may be dependent on cofactor availability. The results also supported the possibility that increased tissue concentrations of adrenal androgens inhibit oestradiol and thus increase tissue exposure to oestradiol.     

17 Beta-hydroxysteroid oxidoreductase activity: age-dependent profile in rat liver and kinetic properties of the hepatic microsomal enzyme in relation to cytochrome P450-dependent steroid hydroxylation

The functional relationship between the microsomal cytochrome P450 and 17 beta-hydroxysteroid oxidoreductase (HSOR) enzymes involved in steroid metabolism was investigated in rat liver. In male and female rat hepatic microsomes the NADPH-dependent conversion of androstenedione (AD) to testosterone (T) was approx. 4-fold greater at 6 weeks of age than in 1 week old animals. In hepatic microsomes from 15 week old rats the activity of the HSOR pathway was greater in males than in females (1.51 compared to 0.80 nmol T formed/min/mg protein). However, oestradiol administration to intact adult male rats did not decrease HSOR activity. Thus, androgen is not essential for maintenance of HSOR enzymes. Instead, it is likely that irreversible androgen imprinting of the HSOR enzyme occurs during the prepubertal period. The in vitro characteristics of HSOR activity were also assessed. The Km for NADH-dependent reduction of AD to T was 9.2 microM and the Vmax was 3.0 nmol/min/mg protein but the NAD-mediated formation of AD from T did not follow Michaelis-Menton kinetics. pH markedly influenced HSOR-mediated AD/T interconversion with 17-ketosteroid reduction facilitated at low pH, and 17 beta-hydroxysteroid dehydrogenation about 2-fold more efficient at pH 8.0 than at pH 5.5. Product steroid activation of HSOR activity was noted. 17 beta-Hydroxysteroids, including T and oestradiol, activated the rate of conversion of AD to T and 17-ketosteroids such as oestrone and AD activated the NAD-dependent dehydrogenation of T. Activation was not observed at low steroid substrate concentrations so that it was not possible to analyse this phenomenon by a conventional kinetic approach.     

Concentrations of steroid hormones, and of prolactin, in washings of the human uterus during the menstrual cycle

Levels of steroid hormones, prolactin and protein were determined in trans-cervical flushings of uteri of 73 consenting women presenting for reversal of sterilization. Median total levels of steroids (pmol), prolactin (mu i.u.) and protein (mg) in the washings were: pregnenolone, 4.22; pregnenolone sulphate, 15.1; progesterone, 1.01; dehydroepiandrosterone (DHEA), 8.92; DHEA sulphate, 368; androstenedione, 2.23; testosterone, 1.04; oestrone, less than 0.7; oestrone sulphate, 0.49; oestradiol, 0.08; prolactin, 23.8; and protein, 5.75. Levels of these components of uterine flushings did not vary significantly between Days 6-10, 11-14, 15-20 and 21-28 after the onset of the previous menstrual period (P greater than 0.05). Uniform levels of free steroids in uterine washings throughout the menstrual cycle, and low free steroid/total protein ratios (all less than 3 pmol/mg), support other evidence for a paucity of steroid-binding proteins in human histotroph. The predominance of DHEA sulphate and of pregnenolone sulphate in human uterine washings is in accord with their abundance in plasma, and may provide an important precursor pool for de-novo steroidogenesis by human embryos before implantation. Our results support the view that human histotroph is a filtrate of plasma.     

Steroid production by dispersed cells from fetal membranes and intrauterine tissues of sheep

The hypothesis was examined that the fetal membranes and the endometrium and myometrium of pregnant sheep have the ability to produce oestrogens and progesterone from exogenous precursors, and that this capacity might change during the course of pregnancy, and in relation to the onset of parturition. Cells were dispersed from samples of myometrium, endometrium, allantois, chorion and amnion from sheep at Day 50, Days 130-135 of pregnancy, and at term, in labour, and were incubated in the presence of pregnenolone and 20 alpha-dihydroprogesterone as potential precursors for progesterone production, and oestrone sulphate and androstenedione as potential precursors for oestrogen production. In addition, the metabolism of radioactive progesterone and oestrone sulphate by the dispersed cells was examined. Pregnenolone was converted to progesterone in significant amounts by dispersed cells from chorion and endometrium only. At Day 130 and at term this conversion was blocked by the addition of trilostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase activity. There was no significant change in the net production of progesterone from exogenous pregnenolone with gestation. 20 alpha-Dihydroprogesterone was converted to progesterone by all tissues, and at each stage of gestation. Formation of progesterone from 20 alpha-dihydroprogesterone was invariably greater than that from pregnenolone, but did not change with pregnancy. Oestrone sulphate was converted to oestrone and oestradiol by all tissues. In the myometrium and chorion this conversion was lower at term than at Day 50 of pregnancy. In contrast, there was very little conversion of androstenedione to unconjugated oestrogen, minimal activity being demonstrable only in dispersed cells from the chorion in some preparations. Radioactive progesterone was converted to radiochemically pure 17 alpha-hydroxyprogesterone by chorion, and to radiochemically pure 20 alpha-dihydroprogesterone by amnion, chorion, allantois and endometrium obtained at term pregnancy. At term [3H]oestrone sulphate was converted to radiochemically pure oestrone by all tissues. We conclude that there is a tissue-specific distribution of different steroid metabolizing enzyme activities in the fetal membranes and intrauterine tissues of pregnant sheep. Of the substrates examined, 20 alpha-dihydroprogesterone and oestrone sulphate were preferred for progesterone and oestrogen production, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

Spontaneous electromyographic activity throughout the cycle in the sow and its change by intrauterine oestrogen infusion during oestrus

Two experiments were carried out to monitor influences on the uterine electromyographic activity (EMG) in cyclic gilts with chronic uterine EMG electrodes. In Exp. 1 the EMG was recorded continuously from Day -1 for 24 days and was evaluated for frequency, duration and amplitude. Progesterone and oestradiol in peripheral plasma were measured daily. As high amounts of oestrogens are characteristic for boar semen, in Exp. 2 the influence of seminal oestrogens on uterine contractions at Day 0 (first day of standing reflex) was investigated in gilts with chronic intrauterine catheters. They were infused with 10 ml saline (N = 4) or saline with physiological amounts of oestrogens (5 micrograms oestradiol + 2 micrograms oestrone + 4.5 micrograms oestrone sulphate; N = 4). Sham-treated gilts (infusion catheters, no infusion; N = 5) served as controls. The EMG was recorded for 2 h before and 9 h after infusion. In Exp. 1 the maximal amplitude (2040 +/- 98 microV) and duration (32 +/- 1.7 sec) but the lowest frequency (15.8 +/- 2.1 contractions/h) were found on Day 0. With decreasing oestrogen and increasing progesterone concentrations the frequency increased continuously until Day 5 (63.5 +/- 1.0 contractions/h) while the amplitude (183 +/- 13 microV) and duration (3.3 +/- 0.7 sec) decreased. During Days 6-13 the EMG activity was not detectable. The reverse pattern was found from the onset of luteolysis until the following Day 0. On Day 0 a significant correlation between oestradiol and the duration (r = 0.81; P less than 0.01; n = 10) but not the frequency was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on the metabolism of oestrone sulphate. Comparative perfusions of oestrone and oestrone sulphate through isolated rat livers

The metabolism of [4-(14)C]oestrone and of [6,7-(3)H(2)]oestrone sulphate was studied during cyclic perfusion and once-through perfusion of the isolated rat liver. The following results were obtained. 1. As shown by once-through perfusion, the two steroids are metabolized differently during the first passage through the organ. [4-(14)C]Oestrone was taken up by the liver and partly delivered as oestradiol-17beta and oestriol into the medium. After uptake of [6,7-(3)H(2)]oestrone sulphate, only oestrone, liberated by hydrolysis, was delivered into the medium; no oestradiol-17beta or oestriol could be detected in the medium after one passage through the organ. This indicates that intracellular oestrone, which was taken up as such, and oestrone, which derived from intracellular hydrolysis, may be metabolized in different compartments of the liver cell. 2. The results of the cyclic perfusion showed that intracellular oestrone is preferentially conjugated with glucuronic acid, and subsequently excreted into the bile. Intracellular oestrone sulphate is preferably reduced to oestradiol sulphate, thus indicating that oestrone sulphate is a better substrate for the 17beta-hydroxy steroid oxidoreductase than is oestrone. 3. Albumin-bound oestrone sulphate acts as a large reservoir, and in contrast with free oestrone is protected from enzyme attack by its strong binding to albumin. 4. Oestrone sulphate is partly converted into the hormonally active oestrone by liver tissue. This suggests that liver not only inactivates oestrogens, but also provides the organism with oestrone, which is subsequently readily taken up by other organs.     

Patterns of plasma progesterone, androgen and oestrogen concentrations and in-vitro ovarian steroidogenesis during embryonic diapause and implantation in the mink (Mustela vison)

Peripheral plasma progesterone concentrations exhibited an increase 10 days before implantation, coinciding with the resumption of blastocyst growth and with a decrease in plasma androgen values (DHA, androstenedione, testosterone). No definite pattern of oestrone was observed and oestradiol concentrations remained undetectable. The production of steroids by dispersed luteal cells showed that the growth of the corpora lutea paralleled that of blastocysts and resulted in hypertrophy followed by hyperplasia of the luteal cell. The production of progesterone in the medium increased with blastocyst size up to implantation; it was enhanced by mink charcoal-treated serum, but prolactin, LH, FSH or a combination of these hormones did not affect the progesterone production, whatever the stage of diapause. DHA and androstenedione secretion increased in the two last stages of blastocyst growth and was enhanced by LH. The conversion of androstenedione and testosterone into oestrone and oestradiol was observed at all stages of embryonic diapause, indicating that corpora lutea contain aromatase activity even at an early stage. The secretion of oestrone was higher than that of oestradiol. The non-luteal tissue contributed up to 50% of the steroid production; while progesterone and androgen production remained constant, that of oestradiol decreased at the end of the delay period. These results indicated a change in the size and the secretory capacity of the luteal cell related to blastocyst development and implantation. Although progesterone was the main product of the corpora lutea, androgens and oestrogens were also secreted.     

Oestrogen synthesis by the foetal rat testis in organ culture

Testes from 19- to 21-day old rat foetuses were bisected and cultured in the presence of tritiated testosterone, androstenedione or dehydroepiandrosterone as precursors for oestrogen biosynthesis. Oestrone and oestradiol formed were identified by recrystallization to constant specific activity, and their conversion rate was determined after isotopic dilution. Both oestrogens formed from either precursor, their conversion rate being about 0.05% for oestradiol and 0.015% for oestrone.     

Conjugated and unconjugated oestrogens in fetal and maternal fluids of the cow throughout pregnancy.

The changes in concentration of oestrone, oestradiol (-17alpha and -17beta), oestrone sulphate and the oestradiol sulphates have been measured in allantoic and amniotic fluids and in maternal peripheral plasma throughout gestation. Oestrone sulphate was the major oestrone present in all of the fluids. It was measurable in allantoic fluid before Day 52 and reached a peak concentration of 475 ng/ml around Day 133. A lower peak occurred in the amniotic fluid around Day 110. The changes in oestradiol sulphates in allantoic fluid were similar to those of oestrone sulphate but at a much lower level. Considerable fluctuation was observed in the oestradiol sulphate concentrations in amniotic fluid. The ratio of oestradiol-17alpha sulphate to oestradiol-17beta sulphate was considerably higher in amniotic fluid than in allantoic fluid. Consistent changes in the levels of oestrone and the oestradiols were found in amniotic fluid but not in allantoic fluid during the second half of pregnancy. In maternal peripheral plasma oestrone sulphate was measurable before Day 72. In the limited number of samples analysed no difference in oestrogen concentration due to the sex of the fetus was evident in any of the fetal or maternal fluids.     

Effects of DHA-S on placental 3 beta-hydroxysteroid dehydrogenase activity, progesterone and 20 alpha-dihydroprogesterone concentrations in placenta and serum

To study the effects of dehydroepiandrosterone sulfate (DHA-S) on placental steroid metabolism and maternal steroidal profiles at term, the following in vivo and in vitro experiments were performed. Two hundred mg of DHA-S was given to five pregnant women 30 minutes prior to delivery. After delivery, the placenta was collected and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and sulfatase activity was determined by measuring the rate of conversion of pregnenolone to progesterone and DHA-S to DHA. The amount of C21-delta 4-steroid in the placental tissue was measured by gas chromatography mass spectrometry (GC-MS) and compared with the control groups. The maternal serum concentration of several steroids was also measured by GC-MS before and after the administration of DHA-S. 3 beta-HSD activity in the placentae from the mothers who received DHA-S before delivery was significantly lower than in the controls. On the other hand, no significant change was observed in the activity of sulfatase. The serum concentration of progesterone (P) and 20 alpha-dihydro-P (20-P) before DHA-S loading decreased following the administration whereas estradiol (E), DHA, and androstenedione (A) levels increased. To study the direct effect of DHA-S and its related steroids on placental 3 beta-HSD activity, placental tissue samples were incubated with pregnenolone in vitro. Several other steroids were added simultaneously into the medium. It was observed that placental 3 beta-HSD activity was directly inhibited by DHA-S. These results indicate that DHA-S inhibits 3 beta-HSD activity in the placenta and subsequently causes a reduction in P and 20-P.     

Deuterium labelled steroid hormones: tracers for the measurement of androgen plasma clearance rates in women

A method employing stable isotope-labelled tracers and gas chromatograph-mass spectrometry (GC-MS) analysis has been used to measure the plasma clearance rates (PCR's) of androstenedione (A) and testosterone (T) in normal women and women with androgen abnormalities including hirsutism and polycystic ovary syndrome. A solution of deuterium-labelled A and T is infused at a constant rate and blood samples taken at 2 and 2.25 h. Solvent extracts of the derived plasma samples, to which an internal standard has been added, are derivatized with pentafluoropropionic anhydride and the endogenous steroid and deuterated steroid are quantitated after an injection of the derivatization mixture into a capillary column GC-MS. The concentration of the deuterated steroid in the infusion mixture is measured and the PCR is calculated. In premenopausal normal women the PCRA is 1950 +/- 184 1/24 h (n = 5) and the PCRT is 484 +/- 82 1/24 h (n = 7).     

Modulation of phospholipase A2 activity in human endometrium and amniotic membrane by steroid hormones

Phospholipase A2 (PLA2) activity was measured in endometrium and amnion by a double isotope ratio technique using 1-palmitoyl-2-oleoyl phosphatidylcholine as substrate in the presence and absence of a range of unconjugated steroids and steroid sulphates (0.2–6.4 × 10⁻⁴ M). In the presence of 0.1% Triton, PLA2 activity was inhibited by the majority of steroids tested, pregnenolone sulphate being the most effective (12.9 ± 3.0% control activity) while oestradiol sulphate, oestrone and testosterone had only a minimal or no effect (99.1 ± 19.0, 85.4 ± 4.4 and 104.2 ± 16.3% control respectively). In the absence of Triton, the inhibitory effect of the free steroids was reduced or absent but oestradiol sulphate and testosterone sulphate stimulated activity by 2–13 and 1.5–3 times respectively. The effect was dose related, linear with time and independent of the stage of the menstrual cycle. Inhibition by pregnenolone sulphate, dehydroepiandrosterone (DMA sulphate and oestrone sulphate was maintained in the absence of Triton (24.9 ± 3.8, 67.1 ± 10.1 and 87.2 ± 13.8% control respectively). In amnion all 5 steroid sulphates caused a marked stimulation of PLA2 activity in both the presence and absence of Triton. The effect was greatest without Triton and at 6.4 × 10⁻⁴ M, testosterone, pregnenolone, oestrone, DHA and oestradiol sulphates increased PLA2 activity 20, 15, 12, 10 and 6-fold respectively. These findings indicate a direct action of steroid sulphates on PLA2 activity in endometrium and amnion.     

Conjugated and unconjugated plasma oestrogens in men with chronic alcoholism and in normal men

The plasma concentrations for unconjugated and conjugated oestrone, oestradiol-17β and oestriol, were measured in 25 male patients with chronic alcoholism and 25 healthy male blood donors of the same age. All persons had normal weight and were free of medication. The patients with chronic alcoholism consisted of 15 persons with and 10 without hepatomegaly. Liver biopsy was performed in the persons with hepatomegaly. Unconjugated oestrogens were separated on LH-20 micro columns after extraction with diethyl ether. Oestrogen sulphates were extracted and separated after hydrolysis with sulphatase, and glucuronides were extracted and separated after hydrolysis with glucuronidase.In the patients with hepatomegaly the plasma concentrations of unconjugated oestrone, oestradiol-17β and oestriol were significantly increased, and the plasma levels for the same oestrogen sulphates were significantly decreased, whereas a moderate increase was observed for oestriol glucuronide. The patients without hepatomegaly revealed a significantly lower plasma concentration for oestrone sulphate, whereas no difference was seen for the remaining oestrogen components. The ratio oestrone sulphate to oestrone was significantly reduced in both groups of patients. A significant decrease for the ratio oestradiol sulphate to oestradiol and oestriol sulphate to oestriol was seen only in the patients with hepatomegaly.     

The effect of glucocorticoids on the in vivo conversion of androstenedione to oestrone

In vitro studies have previously shown that the activity of the aromatase enzyme system, which is responsible for the conversion of androstenedione to oestrone, can be stimulated by natural and synthetic glucocorticoids and also by ACTH. In view of the potential physiological importance of such a regulatory mechanism we have examined the effect of administration of dexamethasone, and of ACTH on the conversion of androstenedione to oestrone in vivo. The transfer constants for the conversion of androstenedione to oestrone [( rho]AEBU) measured in two women before administration of dexamethasone were 1.0% and 1.1% and after were 0.9% and 1.2%. Similarly no increase in conversion of androstenedione to oestrone [( rho]AE1BB) was detected after ACTH stimulation (pre = 0.74%, post = 0.77%). It is concluded from this study that glucocorticoids and ACTH do not have a role in regulating aromatase activity in vivo.