Peripheral E2 Research Articles

Upregulation of Cerebrospinal Fluid and Peripheral Prostaglandin E2 in a Rat Postoperative Pain Model

Analgesic management of postoperative pain associated with thoracic surgery remains a difficult clinical challenge. In the present study we used a thoracic muscle incision model to characterize pain-related behavior and changes in prostaglandin E2 (PGE2) in both thoracic cerebrospinal fluid (CSF) and incision site tissues. A deep muscle incision was made in the left thoracic region of rats anesthetized with isoflurane, propofol, or spinal bupivacaine. Thoracic CSF and incision site tissue concentrations of PGE2 were monitored for 6 h using microdialysis loop catheters. Postoperative pain-related behavior was assessed by recording exploratory locomotive activity. Thoracic muscle surgery decreased rearing and ambulation. Oral ketorolac or rofecoxib 3 mg/kg restored normal rearing and ambulation. Postoperative CSF PGE2 concentration increased most (threefold) with spinal anesthesia, and not at all with propofol. With surgery under isoflurane or spinal bupivacaine, presurgical oral administration of ketorolac or rofecoxib 3 mg/kg reduced postsurgical CSF PGE2 levels and tissue PGE2 levels. Intrathecal ketorolac (4 microg) reduced CSF PGE2 after surgery without affecting tissue PGE2 levels, whereas intrathecal L-745,337 (80 microg) did not reduce CSF PGE2. Thoracic surgical wounds increase pain-related behavior and CSF and tissue PGE2 levels, all of which can be attenuated by oral cyclooxygenase inhibitors.

Investigation of central versus peripheral effects of estradiol in ovariectomized mice

It is generally believed that estrogens exert their bone sparing effects directly on the cells within the bone compartment. The aim of the present study was to investigate if central mechanisms might be involved in the bone sparing effect of estrogens. The dose-response of central (i.c.v) 17beta-estradiol (E2) administration was compared with that of peripheral (s.c.) administration in ovariectomized (ovx) mice. The dose-response curves for central and peripheral E2 administration did not differ for any of the studied estrogen-responsive tissues, indicating that these effects were mainly peripheral. In addition, ovx mice were treated with E2 and/or the peripheral estrogen receptor antagonist ICI 182,780. ICI 182,780 attenuated most of the estrogenic response regarding uterus weight, retroperitoneal fat weight, cortical BMC and trabecular bone mineral content (P<0.05). These findings support the notion that the primary target tissue that mediates the effect of E2 on bone is peripheral and not central.

Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women

Postmenopausal estradiol (E(2)) levels vary widely between individuals and this variation is an important determinant of diseases such as osteoporosis. It has been suggested that the estrogen receptor alpha (ESR1) gene may influence peripheral E(2) levels, but the role of common sequence variations in the ESR1 gene is unclear. In 631 postmenopausal women and 528 men from the Rotterdam Study, a population-based, prospective cohort study of individuals aged 55 years and over, ESR1 PvuII-XbaI haplotypes were determined and correlated with plasma E2 levels. In women, haplotype 1 (T-A) was significantly associated with an allele-dose-dependent decrease in E(2). After adjusting for age, body mass index, years since menopause and testosterone levels, plasma E(2) levels decreased by 1.90 pmol/l per allele copy of this haplotype (P < 0.05). Extreme genotypes, representing 23 and 27% of the population, varied by 3.93 pmol/l. No association with plasma testosterone was observed. In a subset of 446 women, no association of genotype with plasma concentrations of dehydroepiandrosterone sulfate, androstenedione or estrone was seen. In men, none of the sex hormone levels was associated with the ESR1 PvuII-XbaI haplotypes. We have demonstrated a role for genetic variations in the ESR1 gene in determining post-menopausal E(2) levels in women.

The anti-inflammatory effects of 2 Hz electroacupuncture with different intensities on acute carrageenan-induced inflammation in the rat paw

The aim of this study was to investigate the anti-inflammatory effects of low frequency electroacupuncture (EA) with different intensities in carrageenan-injected rat paw. Bilateral 2 Hz EA stimulation with 0.5, 1 and 3 mA were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via needles for 30 min. We first examined the degrees of edema and hyperalgesia using measurements of paw swelling and hot plate latency over 180 min, at 30 min intervals, after the carrageenan injection. The edema and thermal sensitivities of the hind paw induced by a carrageenan-injection were strongly inhibited by EA stimulation, especially at low intensity. At 3 h after carrageenan-injection, we investigated whether the effects of a 2 Hz EA on a carrageenan-induced edema and hyperalgesia are associated with peripheral cyclooxygenase (COX) mRNA induction and prostaglandin E2 (PGE2) synthesis. Although the induction of COX-2 mRNA was inhibited by 2 Hz EA at various intensities, there was no significant change. However, the synthesis of PGE2 induced by a carrageenan injection was significantly attenuated in rat paw with low intensity EA treatment. The data indicate that low frequency EA treatment with relatively low intensity might be a useful therapy for mitigation of inflammatory edema and hyperalgesia through the regulation of COX-2 expression and PGE2 production in a model of peripheral inflammation in rats.

Preovulatory surge patterns of luteinizing hormone, progesterone, and estradiol-17β in broiler breeder hens fed ad libitum or restricted fed

Spontaneous ovulations are induced by preovulatory surges of luteinizing hormone (LH) and progesterone (P4) during ovulatory cycles in birds, but estradiol-17β (E2) levels are relatively constant. Egg production is enhanced in restricted fed (RF) in comparison with ad libitum fed (FF) broiler breeder hens, but changes in concentrations and peripheral patterns of LH, P4, and E2 during ovulatory cycles in broiler breeder hens are poorly documented. The hypothesis of this study was that high resolution patterns of peripheral LH, P4, and E2 during preovulatory surges would not be different between FF and RF broiler breeder hens. Seven FF and 6 RF broiler breeder hens were photostimulated with 16 L:8 D at 22 wk of age. At 28 wk of age, the hens were cannulated for serial blood sampling and switched to a 24L:0D photoperiod to allow preovulatory surges of LH and P4 to run freely. Three days after cannulation, hens were serially bled every 12 min for 36 h. The FF hens were heavier than the RF hens (5.60 ± 0.35 vs. 3.60 ± 0.28 kg, respectively; P < 0.01). During the 10 d before cannulation, total egg production of the FF and RF hens (8.3 ± 1.4 and 6.8 ± 1.3 eggs, respectively; P = 0.08) and normal egg production (5.6 ± 1.8 and 6.5 ± 1.8 eggs, respectively; P = 0.37) were not different. The FF hens, however, had more abnormal eggs than the RF hens (2.7 ± 1.7 and 0.3 ± 0.8 eggs, respectively; P < 0.01). None of the hormonal measurements was different between the FF and RF hens (P > 0.05). The concentrations of hormones for the FF and RF hens, respectively, were as follows: baseline LH (2.79 ± 0.45 vs. 2.94 ± 0.60 ng/mL) and P4 (1.68 ± 0.56 vs. 1.41 ± 0.43 ng/mL), overall mean LH (3.18 ± 0.45 vs. 3.10 ± 0.46 ng/mL) and P4 (2.32 ± 0.55 vs. 2.09 ± 0.91 ng/ mL), preovulatory surge amplitude of LH (5.43 ± 1.27 vs. 3.88 ± 1.24 ng/mL) and P4 (6.08 ± 2.09 vs. 6.71 ± 3.91 ng/ mL), preovulatory surge duration of LH (7.52 ± 1.80 vs. 5.74 ± 3.18 h) and P4 (7.52 ± 1.42 vs. 8.20 ± 1.24 h), and overall mean E2 (0.25 ± 0.05 vs. 0.23 ± 0.05 ng/mL). In conclusion, there were no differences in total egg production or normal egg production between FF and RF broiler breeder hens, but the FF hens laid more abnormal eggs. Also, there were no differences in the concentrations or peripheral patterns of LH, P4, and E2 during preovulatory surges between the FF and RF broiler breeder hens.

Serum and follicular fluid hormonal levels during ovulation induction

Little is known about the effect of clomiphene citrate (CC) and recombinant FSH (rFSH) on intrafollicular hormonal levels when compared with spontaneously ovulating women. Use of CC, an antiestrogen, depends on an intact hypothalamic-pituitary-ovarian axis, in which exogenous gonadotropin medication acts directly on the ovary to induce folliculogenesis. Although not clearly defined, the gonadotropin-dependent development of the human ovarian follicle results in stimulation of the granulosa cells to produce estrogens from androgens. Hence, peripheral E2 levels are commonly measured to assess follicular development.

Angiotensin converting enzyme inhibition of the gonadotropin-stimulated rabbit: effect on estradiol production.

Our purpose was to determine whether angiotensin converting enzyme (ACE) inhibitors affect gonadotropin-stimulated estradiol (E2) production. This was a prospective, masked, randomized, placebo-controlled animal trial. Twenty female New Zealand White rabbits were hyperstimulated with gonadotropins. One-half of the rabbits received concomitant treatment with the ACE inhibitor, enalapril; one-half received concomitant treatment with a placebo. Baseline peripheral E2 (13 +/- 4 vs 11 +/- 2 pg/ml) and angiotensin II (Ang II) (22 +/- 5 vs 27 +/- 7 pg/ml) levels were similar in both groups. Significant inhibition of peripheral Ang II levels was achieved in the enalapril group (32 +/- 6 vs 93 +/- 15 pg/ml; P = 0.005). E2 was significantly higher in the rabbits receiving enalapril versus placebo (369 +/- 58 vs 183 +/- 35 pg/ml, P < 0.03), respectively. By day 10, peripheral E2 had returned to normal levels in both groups (13 +/- 1 vs 13 +/- 1 pg/ml). However, E2 levels in the ovarian effluent were 2.8 times higher in the enalapril rabbits. Peripheral Ang II levels increase after gonadotropin stimulation and ACE inhibitors are able to blunt this increase significantly. ACE inhibition has a significant stimulatory effect on ovarian E2 production. This implies that Ang II may normally inhibit ovarian E2 production in stimulated cycles.

Das ovarielle Hyperstimulationssyndrom

Techniques of assisted fertilization are usually preceded by ovarian stimulation therapies. This implies the risk of development of an ovarian hyperstimulation syndrome (OHS). With this article, clinical relevance, possible pathogenetic mechanisms, diagnosis, therapy and prevention of OHS are discussed. In addition, three patients with severe OHS are presented. Valid parameters for OHS risk assessment are peripheral E2 values as well as number and diameter of follicles. Until now, the mechanisms which lead to severe OHS are unknown, but hCG seems to trigger the development of symptoms, as OHS very rarely occurs without prior hCG application. Symptoms of severe OHS comprise ovarian enlargement, fluid- and electrolyte imbalance, third space fluid accumulation, haemoconcentration and hypercoagulation. Only symptomatic therapy is available. The significance of vascular mediators for the development of OHS is discussed.

Regulation of Ovarian Steroid Biosynthesis by Estrogen during Proestrus in the Rat*

Studies were performed to test the hypothesis that the rapid decline in estradiol (E2) levels on proestrus before ovulation was due to a reduction in androgen substrate for aromatase, and that this decline in androgen was regulated by an estrogen receptor-mediated mechanism. Aromatase activity, concentrations of E2, androstenedione (A), testosterone (T), and progesterone (P4) in follicular, corpora lutea, and ovarian homogenates as well as peripheral E2, A, P4, and LH were measured in cycling rats from 1400-2000 h on proestrus. These parameters were also recorded after the expected E2 surge in animals treated at 1900 h on diestrous day 2 with the antiestrogen keoxifene (20 mg/kg), with or without an ovulatory dose of PMSG at 1600 h on proestrus. In a second experiment, P-450-17 alpha-hydroxylase/C17,20-lyase (P-450(17 alpha] activity was measured in a group of control rats at 1500, 1700, and 1900 h. Aromatase activity remained unchanged, even though serum and ovarian E2 levels were reduced from peak values at 1500 h to basal values at 1800 h (P less than 0.01). Peripheral A as well as ovarian androgens (specifically follicular but not luteal) A and T were also reduced over this time period (P less than 0.01). Although total ovarian P4 remained unchanged, follicular levels rose from 1400-2000 h (P less than 0.01). These reductions in androgens and E2 levels coincided with a marked reduction in follicular P-450(17 alpha) activity. Treatment with keoxifene with or without PMSG prevented the fall in peripheral E2 and A and the increase in peripheral P4 seen in controls. Ovarian and follicular E2, A, and to a lesser extent T were also remained at values similar to those during the E2 surge. Follicular P4 was reduced by both treatments. Neither treatment had any effect on aromatase. These results indicate that the fall in peripheral and ovarian E2 levels before ovulation was due to a decline in aromatizable androgen, through an inhibition of follicular P-450(17 alpha) enzyme activity, which appears to be mediated by an estrogen receptor-regulated mechanism.

Contribution of preovulatory-phase small follicles to the ovarian response in stimulated cycles

The usual criteria for ovulation induction in stimulated cycles take into account the number of follicles greater than 14-16 mm in diameter. We have retrospectively investigated how the presence of small (8-12 mm) follicles at the time of the last scan influences the ovarian response for in-vitro fertilization (IVF). The mean number of small follicles was nearly constant (3.8 to 5.9) and did not correlate with the number of large (greater than 12 mm) follicles in various protocols for ovarian stimulation. In patients stimulated under the influence of a gonadotrophin releasing hormone (GnRH) agonist, the number of small follicles was correlated with the oestradiol (E2) peak level and with the number of recovered oocytes. Our data demonstrate a significant contribution of follicles less than or equal to 12 mm to peripheral E2 levels and oocyte production for IVF.

Influence of the Fetus and Estrogen on Serum Concentrations and Placental Formation of Insulin-Like Growth Factor I during Baboon Pregnancy*

In the present study, we used an in vivo approach to determine whether the fetus and estrogen have direct effects on placental production and serum concentrations of insulin-like growth factor I (IGF-I) in baboons. On day 100 of gestation, fetuses were removed and placentas left in situ (fetectomy). On days 100-155 of gestation after fetectomy, baboons received 50 mg androstenedione pellets sc in increasing numbers (1-3 every 10 days, n = 8), were injected sc with estradiol (E2) benzoate (0.50-2.5 mg/day, n = 8), or were not further treated (n = 6). Placentas were obtained on day 160, and cells were dispersed in 0.1% collagenase, isolated on 50% Percoll, then incubated for 24 h at 37 C in medium 199. Mean (+/- SE) peripheral serum E2 (nanograms per ml) in untreated baboons (n = 5) was 1.33 +/- 0.06 on days 101-160. Fetectomy decreased (P less than 0.001) E2 to 0.28 +/- 0.04, and androstenedione and E2 after fetectomy increased serum E2 to 0.75 +/- 0.08 and 2.51 +/- 0.23, respectively. Serum IGF-I (nanograms per ml) determined by RIA was 182 +/- 6 on days 101-160 in controls. Serum IGF-I increased (P less than 0.001) rapidly after fetectomy to 403 +/- 22 on days 101-160 and fell precipitously to 185 +/- 8 after placental delivery. Androstenedione and E2 treatment after fetectomy decreased IGF-I to 291 +/- 16 and 239 +/- 6, respectively, values similar to those before fetectomy. Uterine vein concentrations of IGF-I were similar to those in peripheral maternal serum, and the same relative treatment effects were observed. IGF-I secretion (picograms per ml/24 h) by placental trophoblasts of fetectomized baboons (80.1 +/- 9.8) was 242% greater (P less than 0.001) than controls (23.4 +/- 4.7) and decreased after fetectomy by androstenedione (56.7 +/- 15.1) and E2 (62.3 +/- 12.8). Thus, removal of the fetus decreased serum E2 and markedly elevated placental production and maternal serum levels of IGF-I, and these effects were largely reversed by androstenedione or E2. We suggest that the fetus, via secretion of estrogen precursors, regulates placental IGF-I production and consequently maternal serum concentrations of IGF-I during primate pregnancy.

Reproductive hormones in menstrual blood.

Menstrual and peripheral blood samples were collected from 19 regularly cycling women on days 1-3 of the menstrual cycle. Menstrual samples were collected with a soft silicone rubber menstrual cup. Hematocrit, PRL, LH, FSH, estradiol (E2), and progesterone (P4) were measured in all samples. Validation studies were carried out for RIAs of PRL, LH, and FSH in menstrual plasma. The menstrual plasma PRL level was significantly higher than its peripheral blood level on day 1 (63.3 +/- 14.7 and 12.1 +/- 2.9 micrograms/L, respectively; t = 3.331; P less than 0.01), and menstrual PRL was significantly higher on day 1 than on day 2 (t = 3.340; P less than 0.01). There was a strong negative correlation between log menstrual PRL concentration and time of onset of menstruation (r = -0.596; P less than 0.01). Menstrual plasma FSH levels were significantly lower than peripheral levels on each of days 1-3 (day 1:t = 4.787; P less than 0.001), and there was a significant positive correlation between menstrual and peripheral levels (r = 0.607; P less than 0.01). By contrast, menstrual plasma LH was significantly higher than the peripheral level on days 1 and 2 (day 1:t = 3.105; day 2:t = 3.180; P less than 0.01), with no correlation between menstrual and peripheral levels. Menstrual E2 was slightly lower than and significantly positively correlated with peripheral E2 (r = 0.646; P less than 0.01). Menstrual P4 was lower than but showed no correlation with peripheral levels. As expected, the menstrual blood hematocrit was less than 0.20 and highly significantly lower than that of peripheral venous blood. These results suggest that PRL is released in substantial amounts from secretory endometrium into the menstrual flow during the first day of menstrual breakdown. LH may also be released in small amounts from menstrual endometrium, while menstrual FSH, E2, and P4 probably arise entirely from the peripheral circulation.

The source(s) of estrogen production in hirsute women with polycystic ovarian disease as determined by simultaneous adrenal and ovarian venous catheterization

To determine the significant source(s) of estrogen production in women with polycystic ovarian disease (POD), 12 women underwent selective adrenal and ovarian vein catheterization, with simultaneous peripheral blood samplings for determination of cortisol, androstenedione (delta 4A), testosterone, estrone (E1), and estradiol (E2). Ovarian vein E2 gradients were observed in 11 of the 12 patients with a mean of 13.4, whereas adrenal blood samples did not demonstrate significant E2 gradients. Seven of 8 patients exhibited ovarian secretion of E1, with a mean gradient of 13.6 times that of peripheral blood, whereas 4 of the 8 adrenal samples showed E1 gradients. The mean value was 1.4 times peripheral levels. No significant correlations were found between peripheral E1 levels and body weight or degree of adiposity, nor was there a relationship between obesity and E1/delta 4A molar ratio in peripheral blood. The subjects with the highest ovarian delta 4A levels had a significant correlation between peripheral delta 4A and E1. Therefore, our data indicate a significant contribution of ovarian E1 secretion to the peripheral E1 pool in addition to the extraglandular conversion of delta 4A to E1. There was general lack of correlation between peripheral E1 concentrations and plasma E2, and these relationships versus body size suggest that the major source of E2 in women with POD was ovarian secretion.

Concentrations of steroids in the utero-ovarian vein blood, serially collected from the two sides of individual baboons, during the follicullar phase

The purpose of this study was to determine and compare the follicular phase steroid hormone secretion into the utero-ovarian vein by the ovary with a dominant follicle and the contralateral ovary in the same baboon. Serial utero-ovarian vein blood from both sides was collected in 25 baboons by the use of a laparoscope on alternate days, starting on day 1 or 3 of the cycle and continuing through 2 to 3 days post-ovulation. Approximately 3–4 days before the day of expected ovulation, samples were collected at 8-hr intervals. Steroids estradiol (E2) and progesterone (P) were measured in all utero-ovarian vein plasma by radioimmunoassay. In the peripheral plasma, E2, P, LH, and FSH measurements were carried out. Concentrations of steroids were significantly higher on the side of the ovulating ovary by day 5 before ovulation. Individual plots however, indicated that some baboons may establish the dominant side as early as day 11 before ovulation. The preovulatory gonadotropins had a differential effect on the two ovaries. For example, E2 values on the ovulatory side ovary declined after increases in LH/FSH, whereas on the contralateral side these values had increased. Both sides showed increases in the level of P with the increases in LH. The mean interval from E2 peak to LH peak was 24 hrs and LH peak to ovulation was 24 hrs.

Interaction of androgens and estrogens in the control of sexual behavior in male Japanese quail

A series of 4 experiments was performed to study the relative contribution of androgens and estrogens in the activation of sexual behavior in castrated male quail. The synthetic androgen methyltrienolone (R 1881) which is not metabolized in androgen target tissues activated sexual behavior in castrated birds and at the dose level of 0.5–1 mg/day/animal had the same potency as testosterone (T). However R 1881 was much more active than T in the induction of cloacal gland growth and activation of crowing, two typically androgen-dependent responses. This suggests that sexual behavior is not controlled by exactly the same mechanism as crowing or cloacal gland growth. In another experiment, estradiol (E2) alone activated sexual behavior but it is only at very high doses which had clear toxic effects that a significant behavioral activation could be observed. This questions the role of E2 as the physiological agent stimulating copulation in intact birds unless it is assumed that centrally administered E2 would be much more active compared to peripheral E2 which is exposed to a very intense peripheral catabolism. In the last two experiments, a clear synergism could be detected between 5α-dihydrotestosterone (5α-DHT) and E2 in the activation of sexual activity and doses of hormones could be defined which had almost no activity by themselves but significantly stimulated sexual behavior when given simultaneously. It was however impossible to define a hormonal treatment with T metabolites which restored behavior to its precastration level, a result very easily achieved with T treatments. Taken together, these data suggest that activation of sexual behavior in quail does not depend only on E2, nor 5α-DHT nor even on their combined action. Considering that specific T receptors which probably do not bind 5α-DHT are present in the brain, it would seem justified to reconsider the possible role played by T itself in the activation of behavior.

Selection of Agents for Enhanced Follicular Recruitment in an in Vitro Fertilization and Embryo Replacement Treatment Program

In summary, although clomiphene alone, two combinations of clomiphene and hMG, and high dosages of hMG alone all resulted in similar degrees of enhanced follicular recruitment at the time of hCG administration, the patients in the group receiving clomiphene alone had significantly fewer follicles at the time of laparoscopy compared with those of the other three groups. Although clomiphene alone is able to produce sufficient enhanced follicular recruitment, it appears that it is necessary for gonadotropin support to be continued to prevent atresia of some of the cohort of follicles. Second, even though we achieved our best results (with respect to number of embryos replaced per patient) with the use of high-dose hMG, we believe that the ovarian hyperstimulation produced by that regimen resulted in an abnormal luteal phase which made establishment of clinical pregnancies less likely. It is certainly possible that the observed short luteal phases might be able to be corrected with supplemental hCG and/or progesterone. Similar to the results of others, our best results (that is, the highest percentage of the establishment of continuing clinical pregnancies) occurred when the regimen of follicular recruitment agents was individualized depending upon the individual patient's response with respect to size and number of follicles and peripheral E2 levels. However, the differences in pregnancy rates among groups were not statistically significant. Although the ideal regimen for enhanced follicular recruitment has probably not yet been determined, it appears that a combination of clomiphene plus concurrent and sequential hMG in individualized dosages offers the best chance for sufficient ovarian stimulation to ultimately increase the number of embryos available for uterine replacement, and at the same time minimize the disruption of the subsequent luteal phase.

Luteal phase serum estradiol and progesterone in in vitro fertilization

One hundred seventy-five cycles in patients with irreparable tubal disease were stimulated by human menopausal gonadotropin/human chorionic gonadotropin for the purpose of in vitro fertilization. The pregnancy rate was found to be related to the height and pattern of serum estradiol (E2) response in the follicular phase. The mean serum E2 and progesterone (P) during the luteal phase showed no statistically significant difference between the pregnant and nonpregnant patients in the series except after luteal day 11. The mean serum E2 in most of the luteal phase days was highest in the high responders followed by the normal and the low responders. However, the mean P values were similar for the high and normal responders but higher than the low responders on cycle days 18, 20, and 22. The mean serum E2 and P in the luteal phase showed no statistically significant difference among the three most common patterns. This was also true for the pregnant and nonpregnant values in each category of height and pattern of response. We concluded that the success and failure of in vitro fertilization was probably less related to the peripheral E2 and P in the luteal phase than to the number and quality of eggs.

Ultrasound measurement of ovarian follicles stimulated by human gonadotropins for oocyte recovery and in vitro fertilization

Ultrasonic monitoring of ovarian follicles and estimation of serum estradiol (E2) were performed in 51 patients in whom oocyte aspiration for in vitro fertilization was planned. All patients received human menopausal gonadotropin and human chorionic gonadotropin. The daily growth rates of ovarian follicles were recorded ultrasonically for 6 days prior to aspiration. Serum plasma E2 was determined daily during the same period. Follicular dimensions based on the volume of aspirated fluid correlated very well with the ultrasonic measurements. Follicular growth was correlated with increasing peripheral blood E2 levels. The mean follicular diameter increased from 10.8 mm 6 days before aspiration to a maximum of 16.0 mm on the day of presumptive ovulation in a group of patients characterized as low E2 responders. In normal and high E2 responders, the values were from 9.7 mm and 10.5 mm to 16.9 mm and 17.6 mm, respectively. The mean sizes of the follicles by ultrasound 20 hours before laparoscopy were 16.0 mm for the right ovary, 16.6 mm for the left ovary, and 18.5 mm in patients with only one ovary. At laparoscopy the mean diameters calculated from the volume of the aspirated fluids were 17.5 mm, 17.4 mm, and 19.3 mm, respectively. Multiple follicles developed in all but 2 of the 51 patients.

FSH, LH, E2, and T in semen and serum in patients with idiopathic oligozoospermia.

The hormonal profile of semen in oligozoospermia showed lower levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) and higher testostrerone (T), than control semen. Compared with peripheral plasma, LH and E2 were raised while T was significantly diminished.

Oestrogen dynamics in adrenal venous effluents in congenital virilizing adrenal hyperplasia.

Four patients with untreated congenital virilizing adrenal hyperplasia (partial 21-hydroxylase deficiency) were studied by bilateral adrenal vein catheterization. Simultaneous right and left adrenal and peripheral blood samples were collected for determination of oestrone (E1) and oestradiol (E2). The concentrations of both were higher in the adrenal effluents than in the peripheral blood samples, indicating their secretion by the adrenals. All patients were also studied during a sequential test of suppression (0.5 h after i.v. administration of 4 mg dexamethasone) and stimulation (5 min after i.v. administration of 250 microgram ACTH 1-24; Synacthen). Mean peripheral E2 concentrations did not change significantly whereas E1 increased above control levels after stimulation. In contrast, suppression of adrenal venous blood concentrations with dexamethasone, and stimulation with ACTH, was demonstrated for every patient. The results indicate that in congenital adrenal hyperplasia the adrenal glands secrete significant amounts of E1 and E2.