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Luteinizing hormone (LH) pulsatility during the oestradiol- and oestradiol/progesterone-induced LH surge in the human female.

Positive feedback reactions were induced in five female volunteers with regular menstrual cycles on the pituitary secretion of luteinizing hormone (LH) during the follicular phase of the cycle by the i.m. administration of oestradiol benzoate ('oestradiol study'), or by oestradiol benzoate followed by progesterone ('oestradiol/progesterone study'). Prior to the administration of the steroids (basal profiles) and during the LH surges following the administration of the steroids (stimulation profiles), blood was drawn at 10-min intervals and the LH pulsatility assessed. The LH pulses occurred at hourly intervals in basal and stimulation profiles, which concurs with data obtained during the normal proliferative phase and the spontaneous mid-cycle surge of the cycle in both the human and the rhesus monkey. Our findings are, however, in sharp contrast with those obtained in the rhesus monkey by the determination of hypothalamic multi-unit activity.

Adult↗

Winter profile of plasma sex steroid levels in free-living male western diamond-backed rattlesnakes, Crotalus atrox (Serpentes: Viperidae).

Recent field studies on the reproductive ecology of western diamond-backed rattlesnakes (Crotalus atrox) from populations in southern Arizona showed significant differences in the concentration of plasma sex steroids (testosterone, T; 5alpha-dihydrotestosterone, DHT; and 17beta-estradiol, E2) throughout the active season (March-October), and peak levels were coincident with the two mating periods (late summer and early spring). There is, however, no information on levels of sex steroids during winter. Similar to most snakes, hibernating individuals of C. atrox are typically inaccessible, but in southern Arizona, where environmental conditions are typically mild during winter, adult males frequently bask at or near the entrances of communal dens. Basking activity, therefore, offers a unique logistical opportunity to assess the complete annual profile of plasma sex steroid levels in males of a temperate reptile in nature. From November to February, we measured levels of plasma T, DHT, and E2 in adult male C. atrox that were located basking at communal dens. Additionally, cloacal, core body, and ambient air temperatures were obtained to investigate potential relationships between body temperatures and levels of sex steroids. Mean levels of T, DHT, and E2 were relatively high, and the concentration hierarchy was T>DHT>E2. Mean levels of T, DHT, and E2 showed no significant variation across the four months of sampling; however, E2 levels decreased progressively. In the annul cycle, sex steroid levels during winter were not basal when compared to values obtained during the active season. Mean cloacal temperatures of basking males were significantly higher than core body temperatures of non-basking males (inside dens) from November-December, and in February, which suggests that one function of winter basking is to elevate body temperatures. Steroid levels, nonetheless, were not significantly correlated with cloacal temperatures. We suggest that future field studies of male C. atrox should: (a) investigate sex steroid levels in non-basking individuals and (b) test whether elevated levels of sex steroids during winter facilitate the large increases that occur in early spring, which are coincident with the second mating season. Our findings on the reproductive biology of C. atrox and other viperids are discussed in the context of the associated-dissociated model of reproduction.

Animals↗

Effect of antenatal steroid administration on the fetal biophysical profile.

PURPOSE: Our objective was to determine whether antenatal steroid administration affects the biophysical profile score in fetuses. METHODS: A prospective study was conducted in 84 fetuses between 28 and 34 weeks' menstrual age at risk of preterm delivery. Two intramuscular injections of 12 mg of betamethasone were given to the mother 24 hours apart. All fetuses underwent biophysical profile testing prior to and between 24 and 48 hours after steroid administration. Biophysical profiles (including nonstress tests) were evaluated by two maternal-fetal medicine specialists blinded to the timing of steroid administration. Neonatal outcome, including Apgar score, menstrual age at delivery, admission to and length of stay in the neonatal intensive care unit, and mortality, was analyzed in all subjects. RESULTS: In 31 (37%; 95 confidence interval, 26.6-47.2%) of 84 cases, the biophysical profile score decreased at least 2 points after steroid administration. The most commonly affected variables were fetal breathing and the nonstress test. There was no significant difference in the neonatal outcome between the fetuses whose biophysical profile decreased and those whose did not. CONCLUSIONS: Biophysical profile scores were decreased in more than one third of fetuses within 48 hours of antenatal steroid administration, but neonatal outcome was not affected. Knowledge of this occurrence could avoid incorrect decision making regarding fetal well-being.

Adult↗

Profiles of plasma sex steroids and gonadotropin in coho salmon, Oncorhynchus kisutch, during final maturation.

The plasma concentrations of estradiol-17 alpha (E2), 17 mu-hydroxy-20 beta-dihydroprogesterone (DHP), progesterone, 11-ketotestosterone (11-KT), testosterone (T), and gonadotropin (GtH) were measured in adult coho salmon (Oncorhynchus kisutch) concomitantly with advancing maturation of the gonads during the spawning season. Concentrations of E2 were higher in females with eggs showing central (premigrating) germinal vesicles, migrating germinal vesicles, or peripheral germinal vesicles than in fish in which the eggs had undergone germinal vesicle breakdown or ovulation. Conversely, plasma levels of DHP were low at central, migrating, and peripheral germinal vesicle stages and then increased dramatically at germinal vesicle breakdown and ovulation. Levels of 11-KT, T, and GtH generally increased with advancing maturity of the eggs. When time rather than degree of maturation was used as a variable, plasma E2 was high in females first returning from the ocean but then dropped off precipitously in fish sampled at the end of the run. Plasma DHP followed the opposite pattern, being low in fish sampled early in the run and high in fish sampled late in the run. No easily discernible patterns emerged from the profiles of the other steroids and GtH, although some significant variation in the concentrations occurred. Even though sampling was initiated at the time when the salmon first returned from the ocean, most of the hormones were not variable in males when viewed according to sampling date or predominant cell type in the testes, which indicates that the males were extremely close to final maturity during the sampling period. Plasma levels of DHP were higher in males that were producing milt than in any other group of males. Concentrations of 11-KT were higher than those of T in all males, but no patterns in the levels of either steroid emerged.

Animals↗

Effects of steroids with different endocrine profiles on the development, morphology and function of the bursa of Fabricius in chickens.

This paper describes the effect of various steroids on the anlage of the bursa of Fabricius in chickens. The steroids were administered by dipping embryonated eggs on the third day of incubation in ethanolic solutions of these steroids. The results with about 30 different steroids show that the capacity to inhibit the development of the bursa does not correlate with the endocrine properties of these steroids as measured in routine screening tests for androgenic, anabolic, progestational and oestrogenic activities or with the relative binding affinities for various endocrine receptors. More elaborate studies with several representative steroids show that testosterone (10 mg/ml), nandrolone (10 mg/ml), 11 alpha-hydroxynandrolone (10 mg/ml), ethylestrenol (1 mg/ml), lynestrenol (1 mg/ml), and Org OD14 [tibolone] (0.1 mg/ml) induce also histomorphological changes in the remaining bursa tissue still present in 10 day- and 53-day old chickens and in the bursa-dependent sites of their spleens (53-day old chickens only). Testosterone and lynestrenol induced smaller changes than nandrolone or ethylestrenol. Tibolone and 11 alpha-hydroxynandrolone were more effective than nandrolone. All drugs, except testosterone and lynestrenol, imparied antibody formation to Newcastle Disease Virus and decreased the serum levels of total IgG, but not of total IgM. Also these effects were not correlated with endocrine properties. In other studies (for references, see text) we found that several of these steroids, notably tibolone, favourably influence the course of spontaneous autoimmune diseases of NZB/W mice and Obese Strain chickens. Since this autoimmunosuppression is likely to be caused by inhibitory effects on bursa or bursa equivalent, we may use this approach for developing medically useful autoimmunosuppressive steroids with minimal endocrine effects.

Animals↗

[Study of profile analysis on urinary free steroids using high performance liquid chromatography with spectrophotometric scanning by photodiode array--application of Girard reagent T for sample preparation].

High performance liquid chromatography (HPLC) has been useful for profile analysis of steroids. However, the conventional extraction of urinary free steroids using urine specimens has some disadvantages because of lots of interfering substances simultaneously extracted from the urine. These substances were usually detected on the chromatogram at the range of relatively short retention time within which some urinary free steroids were heavily contaminated. Therefore it seemed unsuitable for profile analysis of urinary free steroids by HPLC. In this study, we developed a relatively simple and reproducible method for removing the interfering substances by Girard reagent T. In addition, the purity of each extracted free steroids were confirmed by Photodiode Array continuous scanning system, together with 3-dimensional chromatogram as well as contour map analyzed by the attached computer. The extraction procedure was as follows: (1) 10% volume of 24-h specimens of urine included 1 microgram internal standard was charged to Sep-pack C18 cartridge. The cartridge was eluted with 20 micromilligram ethyl acetate and the eluate was evaporated. (2) 10 mg Girard reagent T dissolved in 0.5 micromilligram acetic acid and 0.5 micromilligram ethanol was added to the residue, then left at room temperature for 2 hours. During this time, ketosteroids formed by the action of Girard reagent T turned to be water-soluble hydrazone complex. (3) After the addition of 10 micromilligram cold water, it was adjusted to pH 8 with NaOH and NaHCO3, then washed with 5 volumes of ethyl acetate (non-ketotic fraction). (4) The lower layer were hydrolyzed by adding 0.5 micromilligram concentrated hydrogen chloride and left for an hour at room temperature, then the liberated steroids were extracted with ethyl acetate (ketotic fraction). (5) Ethyl acetate extract was evaporated and redissolved in the mobile phase, then injected to HPLC. To determine the effect of Girard's separation non-ketotic fraction was also applied to HPLC. The results were as follows: (1) 3-dimensional chromatogram and contour map confirmed the effectiveness of our Girard's separation. The chromatogram of ketotic fraction showed the clear separation of the peaks of 4-ene-3-one steroids in ultraviolet absorbance at 246 nm and each steroid peaks were identical to those of the reference steroids. (2) Urinary non-specific substances moving into non-ketotic fraction was complete and satisfactory.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗

A new systematic treatment for infertile women with abnormal hormone profiles.

Five infertile women, with normal menstrual rhythm who had been investigated previously by daily hormone analyses throughout at least one complete menstrual cycle and had shown poor luteal-phase steroid-hormone profiles were treated by a new approach. They were rendered hypogonadotrophic with large doses of a luteinizing hormone releasing-hormone analogue (Hoe 766) and were then treated with exogenous gonadotrophins to induce follicular growth and ovulation. Progesterone production after ovulation in all cases was superior to that observed in the individual patients' without treatment. One patients conceived in her first conception cycle and another in her fourth. This regimen offers a systematic approach to the treatment of unexplained infertility in women with deficient luteal-phase steroid-hormone profiles.

Buserelin↗

Area-under-the-curve monitoring of prednisolone for dose optimization in a stable renal transplant population.

BACKGROUND: Renal transplant recipients were noted to appear cushingoid while on low doses of steroid as part of a triple therapy immunosuppression of cyclosporin A (CsA), prednisolone, and azathioprine. METHODS: The study group comprised adult renal transplant recipients with stable graft function who had received their renal allograft a minimum of 1 year previously (43 studies undertaken in 22 men and 20 women) with median daily prednisone dose of 7 mg (range 3-10). The control group was healthy nontransplant subjects [median dose 10 mg (10-30)]. Prednisolone bioavailability was measured using a limited 6-hour area under the curve (AUC), with prednisolone measured using specific HPLC assay. RESULTS: The median prednisolone AUC/mg dose for all transplant recipients was significantly greater than the control group by approximately 50% (316 nmol x h/L/mg prednisolone versus 218). AUC was significantly higher in female recipients (median 415 versus 297 for men) and in recipients receiving cyclosporin (348 versus 285). The highest AUC was in women on estrogen supplements who were receiving cyclosporin (median 595). A significantly higher proportion of patients on triple therapy had steroid side effects compared with those on steroid and azathioprine (17/27 versus 4/15), more women than men had side effects (14/16 versus 7/22), and the AUC/mg prednisone was greater in those with side effects than without (median 377 versus 288 nmol x h/L/mg). DISCUSSION: The results are consistent with the hypothesis that CsA increases the bioavailability of prednisolone, most likely through inhibition of P-glycoprotein. The increased exposure to steroid increased the side-effect profile of steroids in the majority of patients. Because the major contributor to AUC is the maximum postdose concentration, it may be possible to use single-point monitoring (2 hours postdose) for routine clinical studies.

Adolescent↗

Anabolic steroids--a review of the clinical toxicology and diagnostic screening.

Anabolic steroids have been used by athletes since the 1950s to increase size and strength in order to improve their performance. The abuse of these substances has since expanded to include junior high and high school male and female athletes and non-athletes. The anabolic and androgenic effects of these agents, when taken in the doses needed to produce increases in size and strength, result in significant serious adverse effects involving the skin, liver, cardiovascular, musculoskeletal, endocrine and reproductive systems. Some of these effects are irreversible. It is essential that clinical toxicologists, emergency room physicians and psychiatrists are familiar with the physical and psychological effects, as well as the changes in laboratory parameters, that typically occur from chronic use of anabolic steroids. The toxicities and representative clinical profiles of steroid users are presented, and the methods available for diagnostic screening using psychological testing and urine analysis are also reviewed.

Anabolic Agents↗

Plasma sex steroid and thyroid hormones profile in male water frogs of the Rana esculenta complex from agricultural and pristine areas.

Some chemical compounds used in intensive agriculture have been found to induce estrogenic effects; therefore a histological analysis of the testes and an evaluation of plasma levels of sex steroid, thyroid hormones, and vitellogenin were carried out in adult male water frogs of two coexisting taxa (Rana lessonae and the hemiclonal hybrid Rana esculenta) sampled in agricultural and pristine areas. Differences in seasonal profiles of hormones were found in water frogs living in the agricultural area where the presence of endocrine disrupting compounds was suspected on the basis of a previous study. In R. esculenta, sampled in the pristine area, high androgen levels were found in May; the opposite trend was found for R. esculenta sampled in agricultural areas in which the highest androgen levels were found in September, significantly lower compared with those found in R. esculenta sampled in the pristine area. Low androgen levels were also recorded in R. lessonae males sampled both in pristine and agricultural areas, while the highest levels were found in September. Regarding the trend of estradiol-17beta, an increase of this hormone was found in July both in esculenta and lessonae sampled in the agricultural area, and in the same month an estradiol-17beta peak, even though lower, was also found both in esculenta and lessonae males captured in the pristine area; detectable vitellogenin was found neither in males captured in the agricultural area, nor in those sampled in the pristine one. Moreover, while no significant changes of thyroid hormones were found either in the esculenta or lessonae males sampled in the pristine area, increased T3 and T4 titers were found in July in both esculenta and lessonae captured in the agricultural area. Morphological differences of the testes in males of parental species captured in the agricultural area were also observed. These findings indicate alterations in endocrine and reproductive function in frogs in the agricultural area, that could suggest the presence of endocrine disrupting compounds.

Agriculture↗

Correlation between plasma steroid hormones and vitellogenin profiles and lunar periodicity in the female golden rabbitfish, Siganus guttatus (Bloch).

Characteristics of the lunar reproductive cycle in the golden rabbitfish, Siganus guttatus, were determined by histological observations of ovarian development, and immunological measurements of plasma steroid hormones, estradiol-17beta (E2), testosterone (T), 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP) and 17alpha,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S), and vitellogenin (VTG). Ovarian and plasma samples were collected every week according to the lunar phases from May to July. Weekly change of gonadosomatic index (GSI) showed two peaks at the first lunar quarter in June and July. Yolky oocytes were also observed around this time. Histological observations revealed that the vitellogenic oocytes appeared again 1 week after spawning and developed synchronously. These results suggest that this species is a multiple spawner and the oocyte development is in a group-synchronous manner. Plasma steroid hormones (E2, T, DHP and 20beta-S) and VTG levels changed in parallel with changes in GSI. The peak of plasma VTG level occurred prior to spawning. These cyclic changes of plasma steroid hormones and VTG support the hypothesis that lunar periodicity is the major factor in stimulating reproductive activity of S. guttatus.

Animals↗

Influence of subconjunctival steroid injection on blood glucose profile in diabetic rats.

PURPOSE: The influence of subconjunctival steroid injection on blood glucose concentration was investigated in rats with streptozotocin (STZ)-induced diabetes. METHODS: Adult male Wistar rats with STZ-induced diabetes (n = 10) and normal controls (n = 10) received subconjunctival injections of 0.1 ml of 0.4% dexamethasone or saline. Blood glucose concentrations were measured before and 3, 6, 12, 18 and 24 h after treatment. RESULTS: In the STZ group, subconjunctival injection of steroids (p = 0.0013) or saline (p = 0.0037) significantly increased the blood glucose level 3 h after treatment. In the control group, the blood glucose concentration was not elevated by subconjunctival injection. In both STZ and control groups, the blood glucose concentration was significantly higher after steroid injection than after saline injection throughout the 24 h study period. CONCLUSIONS: Subconjunctival steroid injection induced a significant blood glucose increase in both diabetic and control rats. For diabetic rats, the subconjunctival injection itself constituted stress that resulted in glucose elevation.

Administration, Topical↗

Steroid and thyroid hormone profiles following a single injection of partly purified salmon gonadotropin or GnRH analogues in male and female sea lamprey.

The effects of exogenous administration of gonadotropin-releasing hormone (GnRH) analogues or of a partly purified salmon gonadotropin extract (GTH) on the duration of steroid and thyroid hormone levels were determined in female and male sea lampreys, Petromyzon marinus, tested under differing temperature and reproductive status. Plasma estradiol levels, but not androgens, were significantly elevated in response to the GnRH analogues or GTH injection compared to controls in female and male lampreys. Higher temperature and/or advance in time of maturation appeared to be inversely related to plasma estradiol levels. These data provide further evidence of hypothalamic control over reproductive function in lampreys. Plasma thyroxine was significantly elevated after female lampreys were treated with GTH, GnRHa (10 micrograms/lamprey) or GnRHa (1 microgram/lamprey) compared to controls. The present study is the first to demonstrate that the GnRH analogue stimulated in some way the pituitary-thyroid axis. These data suggest that a GnRH activity may activate both gonado- and thyrotropic secretion or that the endogenous hormone may itself have both functions in one of the most primitive vertebrates, the sea lamprey.

Animals↗

Excretion profiles of some reproductive steroids in the faeces of captive Nepalese red panda (Ailurus fulgens fulgens).

Faecal samples were collected up to once daily from three female Nepalese red panda (Ailurus fulgens fulgens) prior to, during, and after the expected 1995 breeding season. Radioimmunoassay of faecal progestins and oestrogens showed hormone profiles that suggest that this species is a seasonally polyoestrous, induced ovulator. Examination of faecal extracts following high pressure liquid chromatography and using antisera of high specificity, demonstrated at least five faecal progestins but only one major oestrogen, probably oestradiol. Samples from males were collected up to once weekly during the breeding season in 1996, and androgens measured by radioimmunoassay. Faecal androgens fluctuated widely for all males.

Androgens↗

5 alpha-metabolism in finasteride-treated subjects and male pseudohermaphrodites with inherited 5 alpha-reductase deficiency. A review.

Male pseudohermaphrodites (MPHs) with inherited 5 alpha-reductase deficiency and decreased dihydrotestosterone production have a global defect in 5 alpha-metabolism affecting both C19 androgen metabolism and C21 steroid metabolism. However, the decreased 5 alpha-reduction of testosterone to dihydrotestosterone is the only impaired steroid conversion to have clinical consequences, e.g., ambiguous genitalia, impaired prostate differentiation and development, and decreased facial and body hair. The 5 alpha-steroid metabolite profile in the MPHs was compared with that of men with benign prostatic hyperplasia who were administered varying doses of the 5 alpha-reductase inhibitor finasteride. Finasteride was found to be a potent inhibitor of both C19 androgen and C21 5 alpha-steroid metabolism affecting both hepatic and peripheral 5 alpha-metabolism. The 5 alpha-steroid metabolite profile was strikingly similar to that of MPHs with inherited 5 alpha-reductase deficiency. The data suggest that a 5 alpha-reductase gene codes for an enzyme with affinity for multiple steroid substrates.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Determination of fetal bile acids and related steroidal compounds and their profile in neonatal biological fluids].

The unusual bile acids hydroxylated at 1 beta-, 2 beta-, 4 beta-, 6 alpha- and 19-positions of cholic and chenodeoxycholic acids have been found from the meconium, neonatal bile, blood and urine, and amniotic fluid and pregnant urine by GC-MS analysis. These hydroxylated bile acids and their conjugates were synthesized as their references from the corresponding usual bile acids as starting materials, and the simultaneous and high performance analytical methods were developed by GC-MS, HPLC and enzyme immunoassay. The above mentioned unusual bile acids were identified and determined in significant amounts of the total bile acids in the biological fluids from neonates and pregnant women, but not from normal adults. We, therefore, proposed that they should be called as "fetal bile acids". Application of the developed methods was performed for the studies on the dynamic profile of fetal bile acids in developing fetus and neonates, and the clinical diagnosis of the hepatobiliary diseases of infants and congenital bile acid biosynthetic disorders, Zellweger syndrome, celebrotendinus xanthomatosis, 3-oxo-delta 4-steroid 5 beta-reductase deficiency and congenital biliary atresia. Analyses of steroidal hormones, equine estrogens and 18-hydroxycortisol were also described.

Adrenal Cortex Hormones↗

Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: the HERITAGE Family Study.

Obesity has been associated with alterations in plasma steroid hormone concentrations in men. Older men present an altered steroid hormone profile compared to younger individuals, and an increase in body fatness and changes in adipose tissue (AT) distribution are noted with advancing age. Thus, there is a need to examine the relative importance of increased body fatness and changes in AT distribution with advancing age to plasma steroid hormone and sex hormone-binding globulin levels in men. We, therefore, investigated the relationships among age, body fatness, AT distribution, and the plasma steroid hormone profile in a group of 217 Caucasian men (mean age +/- SD, 36.2 +/- 14.9 yr) who covered a wide age range (17-64 yr). Compared to young adult men, older men were characterized by increased adiposity (P < 0.0001) expressed either as body mass index or total body fat mass assessed by underwater weighing. Differences in AT distribution were also noted with a preferential accumulation of abdominal fat as indicated by a larger waist girth (P < 0.0001) and higher visceral AT accumulation (P < 0.0001), measured by computed tomography, in older subjects. Age was associated with decreases (P < 0.0001) in C19 adrenal steroid levels, namely reduced dehydroepiandrosterone (DHEA), DHEA fatty acid ester, DHEA sulfate, as well as androstenedione levels. Androgens, i.e. dihydrotestosterone and testosterone, were also affected by age, with lower levels of both steroids being found in older individuals (P < 0.0005). When statistical adjustment for body fatness and AT distribution was performed, differences in C19 adrenal steroids between the age groups remained significant, whereas differences in androgens and sex hormone-binding globulin concentrations were no longer significant. The present study suggests that age-related differences in plasma steroid hormone levels, especially androgens, are partly mediated by concomitant variation in adiposity in men.

Adipose Tissue↗

Steroid metabolism by avian ovarian cells during follicular maturation.

The profiles of steroid hormones produced by ovarian cells from the domestic hen were examined. Theca cells from the immature, small white follicles (SWFT), the third largest (T3), and largest (T1) preovulatory follicles, and the ruptured, postovulatory follicle (POFT) were incubated for 3 h at 37 degrees with [3H] progesterone (Prog) or [3H] pregnenolone (Preg). Granulosa cells from the largest preovulatory follicle were incubated with [3H] Preg or were coincubated with theca cells and [3H] Preg. The production of specific steroid metabolites was determined on the basis of coelution of radioactivity with known standard compounds, using an isocratic high-pressure liquid chromatography (HPLC) technique. Granulosa cells converted 93% of [3H] Preg substrate to Prog. More Prog was utilized by T3 cells than by T1 and SWFT cells, either when [3H] Prog was the substrate or when coincubated with granulosa cells and [3H] Preg. The major metabolites of Prog were androstenedione, 17-hydroxyprogesterone, and an unidentified compound with an elution time of 53 min. The POFT cells metabolized [3H] Prog to the same extent as T3 cells did, but their profile of steroidogenesis favored production of the unidentified 53 min metabolite. SWFT cells utilized the least amount of [3H] Preg substrate. The results point to marked changes in enzyme activities in theca cells during maturation and following ovulation.

Animals↗