Serum 17beta-estradiol Levels Research Articles

Transient sex change in the immature Malabar grouper, Epinephelus malabaricus, androgen treatment.

To clarify the cause of sex change recovery after the withdrawal of androgen treatment, immature female Malabar grouper were fed a diet containing 17alpha-methyltestosterone (MT) at 50 μg/g for 7 mo and then a normal diet for 6 mo. The MT brought about precocious sex change from immature ovaries to mature testes with active spermatogenesis, including the development of spermatozoa, and sex change reversed soon after MT treatment withdrawal. This result indicates that precocious sex change in immature Malabar grouper with oral MT treatment is impermanent. The expression of three steroidogenic enzymes (Cyp11a, Cyp19a1a, and Cyp11b) in the gonads of the Malabar grouper were analyzed immunohistochemically at the end of the 7-mo treatment. No apparent differences were seen in the expression pattern of these enzymes between the mature testes of MT-treated fish and the immature ovaries of control fish. In addition, serum estradiol-17beta and 11-ketotestosterone levels in treated fish were the same as those in control fish. These results indicate that in the case of immature Malabar grouper MT might have little effect on endogenous steroidogenesis during precocious sex change even though it induced active spermatogenesis in the gonads of treated fish. From these results, we also concluded that MT might have little effect on the steroidogenic endocrine pathway, and this is one cause of sex change recovery after treatment withdrawal.

Fetal growth restriction alters hippocampal 17-beta estradiol and estrogen receptor alpha levels in the newborn male rat

Fetal growth restriction (FGR) is associated with impaired neurodevelopmental outcomes in affected newborns. The pathogenesis of FGR-associated neurodevelopmental impairment implicates abnormal hippocampal function. The steroid hormone estrogen and its receptor, estrogen receptor alpha (ERα), are involved in the normal programming of hippocampal development and structure. However, the impact of FGR on hippocampal estrogen and hippocampal ERα is not well characterized. We hypothesized that FGR will reduce hippocampal and serum levels of 17-beta estradiol and its receptor, ERα, in the newborn rat hippocampus. We further hypothesize that FGR will reduce hippocampal ERα levels in a region-specific manner. To test our hypotheses, we used the well characterized rat model of FGR induced by uteroplacental-insufficiency in the pregnant Sprague-Dawley rat. Hippocampi and serum were obtained from FGR and control day 0 rat pups and examined for hippocampal 17-beta estradiol, serum 17-beta estradiol, and ERα mRNA and protein levels. Immunohistochemistry was performed to examine region-specific ERα staining. FGR decreased hippocampal 17-beta estradiol levels in the hippocampi of male newborn rats but not females. Serum 17-beta estradiol levels were not affected by FGR in either gender. FGR decreased hippocampal ERα mRNA levels in males but not females. Hippocampal ERα protein levels by Western blotting were not affected by FGR. However, FGR decreased apparent ERα staining in the cornu ammonis (CA)1, CA3, and dentate gyrus regions in the hippocampi of male newborn rats but not females. We conclude that FGR affects the programming of hippocampal estrogen and hippocampal ERα levels in the newborn rat in a gender-specific manner.

Comparison of estradiol and progesteron serum levels in ferrets suffering from hyperoestrogenism and ovarian neoplasia

The aim of this study was to determine whether serum levels of 17beta-estradiol and progesterone are significant diagnostic tools for the confirmation of specific reproductive diseases associated with hyperestrogenism. Thirty-one adult ferrets (<i>Mustela putorrius furo</i>) were divided into five groups. The levels of serum 17beta-estradiol differed significantly when comparing females with ovarian tumors (817.80 ± 433.90 pmol/l) to intact (83.50 ± 32.53 pmol/l) and spayed, healthy females (73.17 ± 0.41 pmol/l) as well as to females with prolonged estrus (274.75 ± 192.40 pmol/l). Concentrations of serum progesterone differed significantly when comparing females with ovarian tumours (2.10 ± 1.85 ng/ml) to intact (0.40 ± 0.40 ng/ml) and spayed, healthy females (0.30 ± 0.12 ng/ml). Our study has made it clear that a determination of serum concentrations of 17-beta estradiol and progesterone is not sufficient for distinguishing between prolonged estrus and the presence of ovarian tumours. Therefore, it is advisable to employ other clinical procedures, such as ones allowing organ visualization. Increased concentrations of 17beta-estradiol in ferrets persisted for two weeks after hCG administration. This is particularly important in clinical practice, as negative effects of estrogens on bone marrow could persist for more than 14 days. Therefore, ferrets should be clinically monitored for a longer period of time.

Developmental regulation of the expression of the transferrin receptor and Ki67 in oocytes of the baboon fetal ovary by estrogen

We previously showed that estrogen regulates baboon fetal ovarian follicle development and oocyte integrity. Because iron incorporated into cells by the transferrin receptor is essential for cell/nuclear function, we determined whether fetal oocyte expression of transferrin receptor and the nuclear protein Ki67 were developmentally regulated by estrogen and associated with DNA integrity/fragmentation. Transferrin-receptor expression was minimal at midgestation and abundant in late gestation and localized to the cytoplasm and surface of oocytes of primordial follicles. Expression of transferrin receptor, however, was negligible in oocytes in fetuses in which serum estradiol-17beta levels were suppressed (>95%) by daily maternal treatment between mid- and late gestation with the aromatase inhibitor letrozole and partially restored by treatment with letrozole and estradiol benzoate. Ki67 was localized to pregranulosa and germ cells at midgestation and throughout the oocyte nucleus in late gestation in estrogen-replete fetuses. In contrast, in estrogen-suppressed fetuses, Ki67 was localized to a limited number of foci around the oocyte nucleus. Apoptosis detected in pregranulosa and germ cells at midgestation was not observed in late gestation in estrogen-replete/-suppressed fetuses. We conclude that estrogen regulates fetal oocyte transferrin-receptor expression and that inhibition of receptor development is associated with alterations in Ki67 expression by the oocyte but not apoptosis. Collectively, these results and our previous studies further define the essential role of estrogen in regulating development of follicles comprised of healthy oocytes by the baboon fetal ovary.

Effect of Long-Term Administration of Cross-Sex Hormone Therapy on Serum and Urinary Uric Acid in Transsexual Persons

Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism. This was a prospective study to evaluate the uric acid levels and fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 male-to-female transsexuals (MFTs) and 47 female-to-male transsexuals (FMTs). The subjects were studied at baseline and 1 and 2 yr after starting cross-sex hormone treatment. The baseline levels of uric acid were higher in the MFT group. Compared with baseline, uric acid levels had fallen significantly after 1 yr of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT group. After 2 yr of cross-sex hormone therapy, the FEUA had increased in MFTs (P = 0.001) and fallen in FMTs (P = 0.004). In MFTs, the levels of uric acid at 2 yr were lower in those who had received higher doses of estrogens (P = 0.03), and the FEUA was higher (P = 0.04). The FEUA at 2 yr was associated with both the estrogen dose (P = 0.02) and the serum levels of estradiol-17beta (P =0.03). In MFTs, a correlation was found after 2 yr of therapy between the homeostasis model assessment of insulin resistance and the serum uric acid (r = 0.59; P = 0.01). Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy. The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.

Sex Difference of Adenine Effects in Rats: Renal Function, Bone Mineral Density and Sex Steroidogenesis

Adenine is widely used in clinical field, however, an excess of adenine is harmful. It is known that the feeding of an adenine-rich diet induces renal failure and decreases bone mineral density (BMD) and the serum testosterone level in male rats. However, there is little information about the influence of adenine on female animals. We compared the effects of adenine treatment between male and female rats. Young male and female rats were administered adenine adjusted with distilled water (6 mg/ml, 50 mg/ml and 100 mg/ml) for 8 weeks (3 times/week, 8-16 week old). In male rats, renal failure was induced by 100 mg/ml adenine treatment and renal dysfunction was induced by 50 mg/ml adenine treatment. Bone loss and the reduction of the testosterone level were also caused by both concentrations of adenine. However, the serum testosterone level and BMD in male rats were decreased by 6 mg/ml adenine treatment by which renal dysfunction was not caused. It is suggested that adenine directly affected bone metabolism and sex steroidgenesis in male animals, not through altering renal dysfunction. In female rats, conversely, renal dysfunction was induced only in the 100 mg/ml group, which was somewhat different from the observation in male rats. The serum 17-beta estradiol level and the BMD in female rats were not affected by adenine treatment at all. In conclusion, there is a significant difference of the effects of adenine, which is commonly contained in medicine and general foods, on steroidgenesis and renal function between male and female rats.

Brown Kelp Modulates Endocrine Hormones in Female Sprague-Dawley Rats and in Human Luteinized Granulosa Cells

Epidemiological studies suggest that populations consuming typical Asian diets have a lower incidence of hormone-dependent cancers than populations consuming Western diets. These dietary differences have been mainly attributed to higher soy intakes among Asians. However, studies from our laboratory suggest that the anti-estrogenic effects of dietary kelp also may contribute to these reduced cancer rates. As a follow-up to previous findings of endocrine modulation related to kelp ingestion in a pilot study of premenopausal women, we investigated the endocrine modulating effects of kelp (Fucus vesiculosus) in female rats and human luteinized granulosa cells (hLGC). Kelp administration lengthened the rat estrous cycle from 4.3 +/- 0.96 to 5.4 +/- 1.7 d at 175 mg . kg(-1) body wt . d(-1) (P = 0.05) and to 5.9 +/- 1.9 d at 350 mg . kg(-1) . d(-1) (P = 0.002) and also led to a 100% increase in the length of diestrus (P = 0.02). Following 175 mg . kg(-1) . d(-1) treatment for 2 wk, serum 17beta-estradiol levels were reduced from 48.9 +/- 4.5 to 40.2 +/- 3.2 ng/L (P = 0.13). After 4 wk, 17beta-estradiol levels were reduced to 36.7 +/- 2.2 ng/L (P = 0.02). In hLGC, 25, 50, and 75 micromol/L treatment reduced 17beta-estradiol levels from 4732 +/- 591 to 3632 +/- 758, 3313 +/- 373, and 3060 +/- 538 ng/L, respectively. Kelp treatment also led to modest elevations in hLGC culture progesterone levels. Kelp extract inhibited the binding of estradiol to estrogen receptor alpha and beta and that of progesterone to the progesterone receptor, with IC(50) values of 42.4, 31.8, and 40.7 micromol/L, respectively. These data show endocrine modulating effects of kelp at relevant doses and suggest that dietary kelp may contribute to the lower incidence of hormone-dependent cancers among the Japanese.

Endocrinological and pathological effects of anabolic-androgenic steroid in male rats.

Many athletes use drugs, especially anabolic androgenic steroids (AAS), but there are few reports on the endocrinological and pathological changes in AAS abusers. In this study we reported the results of endocrinological examinations in rats administered AAS and also physical changes. We separated 37 male Wistar rats (7 weeks old) into 3 groups: Group A was medicated with nandrolone decanoate, metenolone acetate, and dromostanolone; Group B with nandrolone decanoate and saline; and Group C was given only saline. They were given subcutaneous injections of the medications or the control vehicle once a week for 6 weeks. Medications were stopped for 4 weeks, and then resumed for another 6 weeks. After that, rats were sacrificed. Serum testosterone level in Group A was significantly higher than that in Group C. Serum dihydrotestosterone in Group A was significantly higher than that in both Groups B and C. Serum estradiol-17beta levels in Groups A and B were significantly higher than that in Group C. In pathological evaluation, heart, testis, and adrenal gland were severely damaged. These findings indicate that there is a high degree of risk related to the use of AAS.

Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells.

Exposure of humans to bisphenol A (BPA), a monomer in polycarbonate plastics and a constituent of resins used in food packaging and dentistry, is significant. In this report exposure of rats to 2.4 microg/kg.d (a dose that approximates BPA levels in the environment) from postnatal d 21-35 suppressed serum LH (0.21 +/- 0.05 ng/ml; vs. control, 0.52 +/- 0.04; P < 0.01) and testosterone (T) levels (1.62 +/- 0.16 ng/ml; vs. control, 2.52 +/- 0.21; P < 0.05), in association with decreased LHbeta and increased estrogen receptor beta pituitary mRNA levels as measured by RT-PCR. Treatment of adult Leydig cells with 0.01 nm BPA decreased T biosynthesis by 25% as a result of decreased expression of the steroidogenic enzyme 17alpha-hydroxylase/17-20 lyase. BPA decreased serum 17beta-estradiol levels from 0.31 +/- 0.02 ng/ml (control) to 0.22 +/- 0.02, 0.19 +/- 0.02, and 0.23 +/- 0.03 ng/ml in rats exposed to 2.4 microg, 10 microg, or 100 mg/kg.d BPA, respectively, from 21-35 d of age (P < 0.05) due to its ability to inhibit Leydig cell aromatase activity. Exposures of pregnant and nursing dams, i.e. from gestation d 12 to postnatal d 21, decreased T levels in the testicular interstitial fluid from 420 +/- 34 (control) to 261 +/- 22 (P < 0.05) ng/ml in adulthood, implying that the perinatal period is a sensitive window of exposure to BPA. As BPA has been measured in several human populations, further studies are warranted to assess the effects of BPA on male fertility.

Cholesterol-fed ovariectomized monkeys are good animal models for human atherosclerosis of postmenopausal women

Although it is well known that the incidence of atherosclerosis is markedly increased in postmenopausal women, antiatherosclerotic effects of estrogen replacement therapies are not clear. One of the reasons for this is due to the lack of appropriate animal models for atherosclerosis of postmenopausal women. Therefore, we attempted to develop an animal model for atherosclerosis of postmenopausal women and examined the antiatherosclerotic effects of estrogen replacement therapy. Adult ovariectomized Japanese monkeys were fed 2% cholesterol diet alone (C-group) or in combination with conjugated estrogen (CE-group) for 30 months. The serum estradiol-17beta levels of the CE-group were varied between 10 and 204.5 ng/dl during treatment. In the C-group, the serum total cholesterol levels were increased from 110 to 270 mg/dl, and atheroma was first observed after 3-months treatment with angioscopy. In the CE-group, the levels of the serum total cholesterol during treatment were 30% lower than those of the C-group, and the aortic lesions were first observed after 12-months treatment with angioscopy. The aortic intimal thickness of the CE-group was 58% of the C-group. This finding showed good agreement with the angioscopic observation. The aortic lesions were of a fibromuscular type in both groups. In conclusion, a cholesterol-fed ovariectomized monkey is an appropriate animal model for atherosclerosis of postmenopausal women. Furthermore, angiofiberscopic and histopathological observations suggested that estrogen replacement therapy was valid for atherosclerosis of postmenopausal women.

Effect of migratory cycle and 17beta-estradiol on splenic leukocyte functions in female black-headed gulls.

The immune function of wild birds is practically unknown. We have studied several functions of splenic leukocytes from the gull Larus ridibundus. Considering that avian physiology is strikingly affected by the seasonal migratory cycle, those functions were analyzed throughout the seasonal cycle. The functions assayed were: adherence to substrate, chemotaxis and lymphoproliferative response to mitogens. Estrogens have been reported to modulate the immune response in mammals; therefore serum levels of 17beta-estradiol were measured in order to find a putative effect of this hormone on the immune response of female gulls. According to our results, gull splenic leukocytes showed a response similar to that reported in mammals and poultry. In regard to the effect of the seasonal migratory cycle, when the gulls arrived from the migratory flight they showed an immunosuppression as we have obtained in chemotaxis and proliferations assays. The immune response increased during the resting period and especially in the premigratory period. We have found a lack of a direct effect of the age of the animals or even the serum estrogen levels in the immune response of the migratory gulls. These results suggest the existence of other hormones and releasing factors, which would modulate the immune response in gulls, or a unique major effect due to the long flight effort.

Terminal phase males stimulate ovarian function and inhibit sex change in the protogynous wrasse Thalassoma duperrey.

Under experimental conditions, the probability of sex change in the protogynous wrasse Thalassoma duperrey is determined largely by an individual's relative size within a social group. Natural populations, however, contain two distinct male phenotypes that may also play a role in regulating sex change. To investigate potential effects of male phenotype, the ability to change sex, ovarian histology and serum estradiol-17 beta levels were examined in females maintained under controlled social settings. Large females housed with smaller or larger terminal phase males had significantly larger gonadosomatic indices than females housed singly, with other females or with smaller initial phase males. Similarly, ovaries of females housed with terminal phase males showed no histological evidence of sex change, whereas large females from other social groupings were in advanced stages of sex change. These results demonstrate terminal phase males inhibit sex change regardless of their size relative to the female. Furthermore, gonadosomatic indices, ovarian histology, and serum estradiol-17 beta levels of females housed with terminal phase males indicate normal ovarian function whereas ovaries of other treatment groups appear quiescent or are undergoing sex change. Consequently, terminal phase males may be required for normal ovarian development which may, in turn, inhibit sex change in T. duperrey.

Involvement of sex steroid hormones in the early stages of spermatogenesis in Japanese huchen (Hucho perryi ).

In higher vertebrates, considerable progress has been made in understanding the endocrine regulation of puberty; however, in teleosts, the regulatory mechanisms of spermatogenesis during the first annual cycle remain unclear. The present study was conducted to understand the regulatory mechanisms of spermatogenesis throughout the different stages of the first spermatogenic cycle and to check the ability of various steroids and hormones to induce in vitro spermatogonial proliferation in Japanese huchen (Hucho perryi ). The results indicate that the serum level of 11-ketotestosterone (11-KT) was positively associated with germ cell type; the level first began to rise with the appearance of late-type B spermatogonia and continued to increase gradually throughout the active spermatogenic stages and spermiogenesis, reaching a peak value 2 wk before spawning, and then declined. During the spermatogenic stages, the serum concentration of 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-DP) was undetectable. Only a small peak was detected with the appearance of spermatocytes and spermatids, and at the time of spawning, the level increased dramatically, reaching its maximum value with the onset of milt production. Despite the high variation in serum levels of 17beta-estradiol (E2) both between months and among the individuals, E2 was found during the whole reproductive cycle. From these results, we concluded that 1) 11-KT is necessary for the initiation of spermatogenesis and sperm production, and it probably plays a role in spermiation, 2) 17alpha,20beta-DP is essential for the final maturation stage, could play a significant role in the mitosis phase and meiosis process, and probably participates in the regulation of spawning behavior, and 3) estrogen is an indispensable male hormone that plays a physiological role in some aspects of testicular functions, especially during the mitotic phase. The three steroids were also able to induce DNA synthesis, spermatogonial renewal, and/or spermatogonial proliferation in vitro.

Maternal endotoxemia results in obesity and insulin resistance in adult male offspring.

Events in utero appear to be important factors contributing to the development of somatic disorders at adult age. The aim of this study was to examine whether maternal immune challenge would be followed at adult age by metabolic and endocrine abnormalities in the offspring. Pregnant rats were given injections of either endotoxin (Escherichia coli lipopolysaccharide; 0.79 mg/kg, ip) or vehicle on days 8, 10, and 12 of gestation. Adult male offspring to lipopolysaccharide-exposed dams were heavier than controls (P < 0.05) and showed increased adipose tissue weights (P < 0.05), elevated food intake (P < 0.05), and increased circulating leptin (P < 0.01). The effect of insulin on glucose uptake was reduced, as measured by an euglycemic hyperinsulinemic clamp technique (P < 0.05). Serum levels of 17beta-estradiol and progesterone were elevated (P < 0.01 and P < 0.05, respectively). Baseline levels of corticosterone were normal, but the corticosterone response to stress was attenuated (P < 0.05), and hippocampal glucocorticoid receptor protein was up-regulated (P < 0.05). Female offspring were uninfluenced, except for increased testosterone levels (P < 0.05), increased baseline corticosterone levels (P < 0.05), and enlargement of heart and adrenals (P < 0.05). The results indicate that maternal endotoxemia leads to obesity, insulin resistance, and high serum levels of leptin in the adult male offspring. This study reports a novel animal model of obesity with features of the metabolic syndrome.

Activation of Ca(2+)-independent nitric oxide synthase by 17beta-estradiol in post-ischemic rat heart.

Nitric oxide (NO) donors or facilitation of endogenous NO production is cardioprotective. This study sought to determine whether enhanced myocardial NO production might contribute to estrogen-induced cardioprotection. Ca(2+)-dependent and Ca(2+)-independent NOS activities (pmol min(-1) mg(-1) protein), NOS protein expression (quantitative immunoblot), cGMP content (pmol mg(-1) protein) and LV work (Joules) were measured in hearts isolated from ovariectomized rats that were either untreated or treated chronically with 17beta-estradiol (0.25 mg, 21 day release formulation). After 14 days, serum levels of 17beta-estradiol were 6+/-1 and 135+/-16 pg ml(-1) in untreated and 17beta-estradiol-treated animals, respectively. After 60 min aerobic working mode perfusion, Ca(2+)-dependent NOS (untreated, 1.47+/-0.36; 17beta-estradiol 1.13+/-0.25) and Ca(2+)-independent NOS (untreated, 0.45+/-0.24; 17beta-estradiol, 0.41+/-0.21) activities, eNOS and iNOS proteins and cGMP content (untreated, 0.64+/-0.08; 17beta-estradiol, 0.76+/-0.12) were not different in the two groups. After 60 min low-flow (0.5 ml min(-1)) ischemia and 30 min reperfusion, Ca(2+)-dependent NOS activities were again similar (untreated, 1.25+/-0.23; 17beta-estradiol, 0.78+/-0.27). However, after reperfusion, Ca(2+)-independent NOS activity (untreated, 0. 39+/-0.10; 17beta-estradiol, 1.36+/-0.36) was 3.5-fold higher (P=0. 008) and cGMP content (untreated, 0.30+/-0.03; 17beta-estradiol, 0. 49+/-0.07) was 1.6-fold higher (P=0.017) in hearts from 17beta-estradiol-treated animals. Although pre-ischemic function was similar, recovery of post-ischemic LV work was 2-fold greater (P=0.024) in the 17beta-estradiol group. The ability of ischemia and reperfusion in combination with chronic 17beta-estradiol to increase Ca(2+)-independent NOS activity and cGMP content supports a role for enhanced myocardial NO signaling in 17beta-estradiol-induced cardioprotection.

Normal development of thymus in male and female mice requires estrogen/estrogen receptor-alpha signaling pathway.

Estrogen receptors (ERs) are expressed in the thymus of both males and females, but their role in thymic development and function is unclear. To determine whether ERalpha plays a role in thymic function of either males or females, we compared thymuses of male and female wild-type (WT) and ERalpha knockout (alphaERKO) mice from birth to adulthood. Although thymic size was similar in both male and female WT and alphaERKO mice at birth (d 0), by postnatal d 5 and at all subsequent ages, both male and female alphaERKO mice had significant (30-55%) reductions in thymic weight. Morphometric analysis revealed a reduction in thymic medullary areas in adult alphaERKO mice compared with age-matched WT controls that paralleled thymic involution. There were changes in relative percentages of CD4+ and CD4+CD8+ T-cells, and large decreases (70-80%) in overall absolute numbers of CD4+ and CD4+CD8+ T-cells. Serum corticosterone and testosterone levels were not different in either neonatal or adult male WT or alphaERKO mice, and serum levels of 17beta-estradiol (E2) were similar in neonatal WT and alphaERKO males, indicating that increases in these thymolytic hormones are not responsible for the decreased thymic weight in alphaERKO males. Additionally, delayed-type hypersensitivity was significantly increased in male alphaERKO mice compared with WT mice. In summary, ERalpha deficiency does not inhibit initial differentiation or fetal thymic development, but the absence of ERalpha results in marked decreases in thymic size in both sexes during the postnatal period. These results are the first direct demonstration that the E2/ERalpha signaling system is necessary for maintenance of normal postnatal function of the female thymus gland. The similar results obtained in males demonstrate a role for the E2/ERalpha signaling system in the male thymus and emphasize that estrogens play a more critical role in the male than previously realized.

Successful co-treatment with LHRH-agonist for ovarian over-stimulation and cystic formation in premenopausal tamoxifen exposure.

The present study evaluates the potential beneficial effect of co-treatment with LHRH-agonist in resolving premenopausal tamoxifen's induced supraphysiological serum 17beta estradiol levels and persistent ovarian cysts. Ultrasonographic and serum hormonal evaluations were performed before, during, and following three consecutive injections of long acting LHRH-agonist administered to 14 premenopausal breast cancer patients treated with tamoxifen, who had supraphysiological serum 17beta estradiol levels and simultaneous persistent ovarian cysts. Within 3 weeks of the first LHRH-agonist injection, all patients had menopausal serum estradiol levels. Ovarian cysts completely disappeared within 2 months following the first injection. Following the discontinuation of LHRH-agonist co-treatment, serum estradiol levels remained in physiological levels and the ovaries remained a normal size in 64.3% of the patients for 13.3 +/- 11.5 months. 28.6% of the patients had a gradual reappearance of high serum estradiol levels and of ovarian cysts, and were, therefore, treated with a second course of LHRH-agonist. Following the second course, serum estradiol levels remained in physiological levels and the ovaries remained a normal size for 8-15 months. It is concluded that short duration of co-treatment with long acting LHRH-agonist administered to premenopausal breast cancer patients treated with tamoxifen, successfully resolved the tamoxifen-induced supraphysiological serum 17beta estradiol levels and the ovarian cysts.

Equine fescue toxicosis: signs and solutions.

Gravid mares grazing endophyte-infested (E+) tall fescue exhibit increased gestation lengths, agalactia, foal and mare mortality, tough and thickened placentas, weak and dysmature foals, increased sweating during warm weather, reduced serum prolactin and progesterone, and increased serum estradiol-17 beta levels. Also, E+ tall fescue hay is less digestible than endophyte-free (E-) hay. Unlike many other species, horses consuming E+ tall fescue do not exhibit increased body temperature. Young horses consuming only E+ pasture do not gain as well as those consuming E- pasture. There is little difference in gain when the pasture is supplemented with enough concentrate to meet NRC requirements for growth. Neither selenium injections nor supplementing with corn at 50% of the NRC requirements for energy reduces the effects of toxic tall fescue on reproduction and lactation in gravid mares. It seems that the alkaloids of E+ tall fescue are serving as D2 dopamine receptor agonists. This activity would explain their prolactin-lowering effect. Domperidone, a dopamine receptor antagonist, is effective in preventing the signs of tall fescue toxicosis in horses without neuroleptic side effects.

RELIABILITY OF IMMUNORADIOMETRIC ASSAYS FOR SEX-HORMONE BINDING GLOBULIN, ANDROSTENEDIONE, 17-BETA ESTRADIOL AND TUMOR-MARKERS CEA AND CB15.3 TO ASSESS THE BIOLOGICAL RESPONSE OF MEGESTROL-ACETATE TREATMENT IN PATIENTS WITH ADVANCED BREAST-CANCER

This study evaluated the effect of megestrol acetate administration on the serological assessment of some sex steroid hormones in women with advanced hormone-sensitive breast cancer. The serum levels of 17-beta estradiol, androstenedione and sex hormone binding globulin (SHBG) were measured by means of radioimmunometric assays, before and during drug administration. A significant suppressive effect on SHBG and androstenedione levels in comparison with the baseline values was reached in 100% (40/40) and 51% (20/39) of patients, respectively, after two months of therapy; by contrast, 17-beta estradiol levels showed an increase above the baseline levels in 18 out of 22 patients. These findings might be explained on the basis of a possible interference in vivo of megestrol acetate metabolites particularly in the estradiol assay, since a direct influence of the solubilized megestrol acetate was not observed in vitro. The hormone levels generally did not shaw any relationship with the course of the disease, so their serial determinations do not seem to be useful to assess the clinical status or evaluate response to therapy. In our group of patients, CEA and CA15.3 serum determinations were also carried out to monitor the efficacy of treatment. CEA and CA15.3 levels reflected the course of the disease in 58.9% (23/39) and 65.8% (25/38) of patients, respectively. The two tumor markers displayed a similar sensitivity in detecting cancer progression (64% CEA and 63% CA15.3), but CA15.3 seemed to have a better diagnostic value in evaluating the response to therapy and signalling tumor relapse.

Effects of natural progesterone on the morphology of the endometrium in patients with primary ovarian failure

In 43 patients without ovaries, endometrial biopsies at day 21 of 75 substituted cycles were studied by light and electron microscopy. The morphology of the endometrium was compared after oral, vaginal or intramuscular administration of progesterone, and correlated with the serum levels of 17-beta oestradiol and progesterone and the pregnancies obtained after oocyte donation. After vaginal application of micronized progesterone, endometrial morphology closely matched that of a natural cycle. This therapy was able to support two ongoing pregnancies. No adequate endometrial response was noted after oral ingestion of progesterone. The maturation of the endometrium after intramuscular injections of progesterone in oil was heterogeneous. It was concluded that the vaginal route for administering micronized progesterone can be advised as the treatment of choice in patients without ovarian function.