Biomedical subjects

Bill L Lasley

Publications and source records attributed to Bill L Lasley.

32 records · Page 2Linked to original sources

PubMed2003

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on chorionic gonadotrophin activity in pregnant macaques.

As many as 62% of all human conceptions are lost prior to 12 weeks of pregnancy and it is unknown how many of these losses result from environmental hazards. Previous studies have shown that single doses of 1, 2, and 4 microg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administrated orally to cynomolgus macaques during the peri-implantation period leads to early fetal loss (EFL) within 10-20 days. TCDD induced EFL is associated with a reduction in the biological activity of monkey chorionic gonadotrophin (mCG) but no change in the immunoreactive mCG profile. These studies are consistent with either a direct effect of TCDD on differentiation of the trophoblast and an indirect effect on mCG synthesis, or a direct effect on mCG synthesis and secretion independent of trophoblast development. The present study was designed to test the hypothesis that the action of TCDD is directly on mCG synthesis rather than on the differentiation of the trophoblast. Female macaques (Macaca fascicularis) were treated with a single dose of TCDD (4 microg/kg b.wt.) on Gestational Day 20, a stage of pregnancy following initial trophoblast differentiation and invasion. Circulating mCG concentrations were monitored for the next 6 days. Compared to the controls, the peak level of serum bioactive mCG was lower in the treated group (P<0.05), with a decrease observed on the day following exposure. The bioactive/immunoreactive mCG ratio was also lower in the treated group compared to the controls (P<0.05). There was no difference in serum immunoreactive mCG levels between the groups. Histological evaluation of the embryo-placental unit showed increased apoptosis and vascular congestion after treatment but was otherwise grossly normal. Because exposure of the conceptus to TCDD following differentiation of the trophoblast decreased the bioactivity of circulating mCG, we conclude that the action of TCDD in the placenta is directly on mCG synthesis.

Animals↗

PubMed2003

Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status.

We measured serum reproductive hormone concentrations in a community-based, multiethnic population of premenopausal and early perimenopausal women to determine whether there are ethnic differences in hormones that can be explained by host factors. We studied 2930 participants in the Study of Women's Health Across the Nation who were aged 42-52 yr and self-identified as African-American (27.6%), Caucasian (47.1%), Chinese (7.4%), Hispanic (8.8%), or Japanese (9.0%) at 7 clinical sites. Outcome measures from this baseline assessment of a longitudinal study were serum estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate, and SHBG concentrations and calculated estimates of free steroid availability, free testosterone index, and free E2 index from serum collected primarily in the early follicular phase of a spontaneous menstrual cycle. The primary explanatory variables were race/ethnicity, menopausal status, age, body mass index, day of the cycle, smoking, alcohol use, and physical activity. Chinese women had lower unadjusted E2 and SHBG levels, and Hispanic women had lower unadjusted T levels than other ethnic groups. Unadjusted serum FSH levels did not differ by race/ethnicity. E2 levels adjusted for host characteristics, particularly body size, did not differ by race/ethnicity. Adjusted FSH levels were higher, and adjusted T levels were lower in African-American and Hispanic women. Serum E2 and FSH concentrations were highly variable. Serum FSH levels, but no other hormone concentrations, were positively correlated with menopausal status. Serum dehydroepiandrosterone sulfate levels were negatively correlated with age, but not menopausal status. All hormone concentrations were significantly correlated with body mass index. We conclude that serum sex steroid, FSH, and SHBG levels vary by ethnicity, but are highly confounded by ethnic disparities in body size.

Adult↗

PubMed2003

Luteal phase deficiency in recreational runners: evidence for a hypometabolic state.

Exercising women with amenorrhea exhibit a hypometabolic state. The purpose of this study was to evaluate the relationship of luteal phase deficient (LPD) menstrual cycles to metabolic hormones, including thyroid, insulin, human GH (hGH), leptin, and IGF-I and its binding protein levels in recreational runners. Menstrual cycle status was determined for three consecutive cycles in sedentary and moderately active women. Menstrual status was defined as ovulatory or LPD. Subjects were either sedentary (n = 10) or moderately active (n = 20) and were matched for age (27.7 +/- 1.2 yr), body mass (60.2 +/- 3.3 kg), menstrual cycle length (28.4 +/- 0.9 d), and reproductive age (14.4 +/- 1.2 yr). Daily urine samples for the determination of estrone conjugates, pregnanediol 3-glucuronide, and urinary levels of LH were collected. Blood was collected on a single day during the follicular phase (d 2-6) of each menstrual cycle for analysis of TSH, insulin, total T3, total T4, free T4, leptin, hGH, IGF-I, and IGF binding protein (IGFBP)-1 and IGFBP-3. Among the 10 sedentary subjects, 28 of 31 menstrual cycles were categorized as ovulatory (SedOvul). Among the 20 exercising subjects, 24 menstrual cycles were included in the ovulatory category (ExOvul), and 21 menstrual cycles were included in the LPD category (ExLPD). TSH, total T4, and free T4 levels were not significantly different among the three categories of cycles. Total T3 was suppressed (P = 0.035) in the ExLPD (1.63 +/- 0.07 nmol/liter) and the ExOvul categories of cycles (1.75 +/- 0.8 nmol/liter) compared with the SedOvul category of cycles (2.15 +/- 0.1 nmol/liter). Leptin levels were lower (P < 0.001) in both the ExOvul (5.2 +/- 0.4 microg/liter) and the ExLPD categories of cycles (5.1 +/- 0.4 microg/liter) when compared with the SedOvul category of cycles (13.7 +/- 1.7 microg/liter). Insulin was lower (P = 0.009) only in the ExLPD category of cycles (31.9 +/- 2.8 pmol/liter) compared with the SedOvul (60.4 +/- 8.3 pmol/liter) and ExOvul (61.8 +/- 10.4 pmol/liter) categories of cycles. IGF-I, IGFBP-1, IGFBP-3, IGF-I/IGFBP-1, IGF-I/IGFBP-3, and hGH were comparable among the different categories of cycles. These data suggest that exercising women with LPD menstrual cycles exhibit hormonal alterations consistent with a hypometabolic state that is similar to that observed in amenorrheic athletes and other energy-deprived states, although not as comprehensive. These alterations may represent a metabolic adaptation to an intermittent short-term negative energy balance.

Adult↗

PubMed2003

Bone resorption is affected by follicular phase length in female rotating shift workers.

Stressors as subtle as night work or shift work can lead to irregular menstrual cycles, and changes in reproductive hormone profiles can adversely affect bone health. This study was conducted to determine if stresses associated with the disruption of regular work schedule can induce alterations in ovarian function which, in turn, are associated with transient bone resorption. Urine samples from 12 rotating shift workers from a textile mill in Anqing, China, were collected in 1996-1998 during pairs of sequential menstrual cycles, of which one was longer than the other (28.4 vs. 37.4 days). Longer cycles were characterized by a prolonged follicular phase. Work schedules during the luteal-follicular phase transition (LFPT) preceding each of the two cycles were evaluated. All but one of the shorter cycles were associated with regular, forward phase work shift progression during the preceding LFPT. In contrast, five longer cycles were preceded by a work shift interrupted either by an irregular shift or a number of "off days." Urinary follicle-stimulating hormone levels were reduced in the LFPT preceding longer cycles compared with those in the LFPT preceding shorter cycles. There was greater bone resorption in the follicular phase of longer cycles than in that of shorter cycles, as measured by urinary deoxypyridinoline. These data confirm reports that changes in work shift can lead to irregularity in menstrual cycle length. In addition, these data indicate that there may be an association between accelerated bone resorption in menstrual cycles and changes of regularity in work schedule during the preceding LFPT.

Adult↗

PubMed2003

Urinary estrone conjugate and pregnanediol 3-glucuronide enzyme immunoassays for population research.

BACKGROUND: Monitoring of reproductive steroid hormones at the population level requires frequent measurements, hormones or metabolites that remain stable under less than ideal collection and storage conditions, a long-term supply of antibodies, and assays useful for a range of populations. We developed enzyme immunoassays for urinary pregnanediol 3-glucuronide (PDG) and estrone conjugates (E1Cs) that meet these criteria. METHODS: Enzyme immunoassays based on monoclonal antibodies were evaluated for specificity, detection limit, parallelism, recovery, and imprecision. Paired urine and serum specimens were analyzed throughout menstrual cycles of 30 US women. Assay application in different populations was examined with 23 US and 42 Bangladeshi specimens. Metabolite stability in urine was evaluated for 0-8 days at room temperature and for 0-10 freeze-thaw cycles. RESULTS: Recoveries were 108% for the PDG assay and 105% for the E1C assay. Serially diluted specimens exhibited parallelism with calibration curves in both assays. Inter- and intraassay CVs were <11%. Urinary and serum concentrations were highly correlated: r = 0.93 for E1C-estradiol; r = 0.98 for PDG-progesterone. All Bangladeshi and US specimens were above detection limits (PDG, 21 nmol/L; E1C, 0.27 nmol/L). Bangladeshi women had lower follicular phase PDG and lower luteal phase PDG and E1Cs than US women. Stability experiments showed a maximum decrease in concentration for each metabolite of <4% per day at room temperature and no significant decrease associated with number of freeze-thaw cycles. CONCLUSIONS: These enzyme immunoassays can be used for the field conditions and population variation in hormone metabolite concentrations encountered in cross-cultural research.

Adult↗

PubMed2003

Hormonal characteristics in the early luteal phase of conceptive and nonconceptive menstrual cycles.

To determine whether serum hormone profiles are different in nonconceptive and conceptive menstrual cycles after ovulation and before implantation. Daily blood samples obtained during the luteal phase of nonconceptive cycles (n = 31) and conceptive cycles (n = 19) were analyzed (intersubject comparison). Samples obtained in sequential nonconceptive and conceptive cycles from five subjects (intrasubject comparisons) were analyzed to confirm results obtained with intersubject analysis. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E(2)), progesterone, and relaxin were measured by immunoassay. A cell-based bioassay was used to determine whether the measurement of serum immunoreactive LH is a result of cross-reaction with human chorionic gonadotropin (hCG). Intersubject analysis showed that mean serum LH levels were significantly higher in conceptive cycles on day 4 and day 5 after the FSH peak in urine, and this was confirmed by intrasubject analysis. The addition of antibodies that precipitate hCG did not affect the activity of LH receptor ligand molecules in serum samples collected during the early luteal phase of conceptive cycles, as measured by bioassay. In contrast, this LH receptor binding activity was completely removed when precipitating antibodies for LH were added. The mean levels of serum E(2) were higher in conceptive cycles after day 4 following the FSH peak in urine. The mean values of serum FSH, progesterone, and relaxin were not significantly different in nonconceptive and conceptive cycles during the same time interval. The differences in luteal phase hormones may reflect alterations in signaling in the hypothalamic-pituitary-ovarian axis that begin during the preovulatory period of nonconceptive cycles.

Adult↗

PubMed2002

Comparison of chorionic gonadotropin expression in human and macaque (Macaca fascicularis) trophoblasts.

We have designed novel DNA primers that allow us to detect the expression of the subunits of chorionic gonadotropin (CG) from a variety of species of the order Primates. Using these primers, reverse transcriptase-polymerase chain reaction (RT-PCR), and standard cloning techniques, we detected the expression of a single gene for the common glycoprotein hormone (GPH) alpha-subunit and at least two genes for the CG beta-subunit in trophoblasts of Macaca fascicularis (cynomolgous macaque (cm)) at gestational day (GD) = 26 (+/- 2d). No cmCG expression was detected at GD = 35-40. When sequences of cmGPH-alpha and cmCG-beta genes were compared to the corresponding genes of other primates, we found that the alpha-subunit of M. fascicularis was highly conserved compared to other primate species. However, cmCG beta-subunits appeared to be less conserved, residing between those of human CG-beta and baboon CG-beta when analyzed phylogenetically. Of particular interest was a three amino acid stretch in one of the expressed cmCG-beta genes that is distinct from all other primates studied. Our findings imply that not only does the expression of multiple CG beta-subunit genes appear to be common to Old World monkeys, but that the presented methodology will greatly facilitate our ability to understand primate evolution.

Animals↗

PubMed2002

Urinary follicle-stimulating hormone peak as a biomarker for estimating the day of ovulation.

OBJECTIVE: To evaluate urinary follicle-stimulating hormone (FSH) as a biomarker for the day of ovulation. DESIGN: Prospective observational study. SETTING: Clinical research center. PATIENT(S): Thirteen women were monitored with measurements of serum and urinary hormones and ovarian ultrasonography during 20 menstrual cycles. Data on urinary hormones and ultrasound evaluations from a total of 65 menstrual cycles from 42 women were analyzed. INTERVENTION(S): Blood and/or urine samples were collected daily. Daily transvaginal ultrasonography was used to detect follicular collapse. MAIN OUTCOME MEASURE(S): LH, FSH, and E(2) were measured in serum. FSH, estrone conjugates (E1C), and pregnanediol-3-glucuronide (PdG) were analyzed in urine. The day of luteal transition (DLT) was calculated using two algorithms. RESULT(S): In 20 cycles, the urinary FSH peak was closer to the day of follicular collapse (-0.85 days) than was the peak day of serum E(2) and the day of luteal transition, as calculated by one algorithm. The FSH peak was not closer to the day of follicular collapse than the peak values of urinary LH, serum FSH, or the day of luteal transition as calculated by a second algorithm. The most consistent correspondence between a hormone peak and ovulation was for serum E(2), serum FSH, serum LH, and urinary FSH. In 65 cycles for which urinary hormone data and ultrasound evaluations were available, the urinary FSH peak occurred within 1 day of follicular collapse in 97% of cycles. CONCLUSION(S): Urinary FSH is a useful biomarker for estimating the day of ovulation in population-based studies.

Adult↗

PubMed2002

Effect of estrogen and 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) on plasma fatty acids of immature male chickens (Gallus domesticus).

This study investigated the effects of 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) and estrogen on plasma lipids in immature male chickens. Fatty acids were quantified in plasma collected on day 14 from chickens injected with either: Estrogen plus TCDD-1 mg estradiol cypionate /kg body wt. daily for 3 days and 50 microg TCDD/kg body wt. on day 4; Estrogen--1 mg estradiol cypionate/kg body wt. daily for 3 days and vehicle only on day 4; TCDD-vehicle only for 3 days and 50 microg TCDD/kg body wt. on day 4; or Vehicle--same volume of appropriate vehicle for 4 days. TCDD treatment alone increased the plasma concentrations of total triacylglycerides and of the specific fatty acids 14:0, 15:0, 18:0, 18:2n6, 18:3n3, 20:0, 20:1n9, 20:2n6, 20:3n6, 20:5n3 and 22:1n9, compared with vehicle treatment. The concentration of 22:6n3 was increased in all plasma lipid classes of the estrogen group compared with the vehicle group, but was not increased in the estrogen plus TCDD group. Overall, TCDD treatment alone increased plasma lipids, possibly as a result of decreased clearance or utilization; whereas estrogen plus TCDD treatment antagonized estrogen-induced increases in 22:6n3 but did not cause hyperlipidemia.

Adipose Tissue↗

PubMed2002

Effects of prune consumption on the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone.

BACKGROUND: A higher urinary ratio of the biologically inactive estrogen metabolite, 2-hydroxyestrone (2OHE1), to the biologically active metabolite, 16alpha-hydroxyestrone (16alphaOHE1), may be associated with a lower risk of breast cancer. High fiber intake is also associated with decreased breast cancer risk. OBJECTIVE: We investigated the effects of prunes, which are naturally rich in both soluble and insoluble fiber, on the concentrations of 2OHE1 and 16alphaOHE1 and on the ratio of 2OHE1 to 16alphaOHE1. DESIGN: Nineteen healthy premenopausal women consumed their habitual diets for 3 menstrual cycles and then consumed 100 g prunes/d for the next 3 cycles. Concentrations of urinary 2OHE1 and 16alphaOHE1 were determined during the follicular and luteal phases. RESULTS: Prune supplementation increased total and soluble fiber intakes by 4 and 2 g/d, respectively (P < 0.001). Mean (+/- SEM) luteal 2OHE1 excretion decreased from 3.92 +/- 0.79 to 2.20 +/- 0.40 nmol/mmol creatinine during the third cycle (P = 0.017). Luteal 16alphaOHE1 excretion decreased from 1.38 +/- 0.24 to 0.87 +/- 0.10 and 0.87 +/- 0.15 nmol/mmol creatinine during the first and third cycles, respectively (P = 0.018 for both values). Follicular 16alphaOHE1 excretion decreased significantly only during the first cycle (from 0.82 +/- 0.12 to 0.45 +/- 0.09 nmol/mmol creatinine; P = 0.005). The 2OHE1-16alphaOHE1 ratio did not change significantly after prune supplementation. CONCLUSIONS: Prune supplementation significantly decreased the excretion of 16alphaOHE1 during the follicular phase of the first menstrual cycle and during the luteal phases of both the first and third menstrual cycles. The 2OHE1-16alphaOHE1 ratio did not change significantly. The potential significance of the decrease in 16alphaOHE1 excretion, without a change in the 2OHE1-16alphaOHE1 ratio, on the prevention of estrogen-dependent cancers remains to be determined.

Body Composition↗

PubMed2002

Effects of soy consumption on gonadotropin secretion and acute pituitary responses to gonadotropin-releasing hormone in women.

Soy contains the isoflavone phytoestrogens, genistein and daidzein. These isoflavones are partial estrogen agonists in cell and animal models, but effects from dietary soy in humans are unclear. Experiments were conducted in pre- and postmenopausal women to examine whether dietary isoflavones from soy behave as estrogen agonists, antagonists or have no effect on the estrogen-sensitive pituitary. Pituitary sensitivity to gonadotropin-releasing hormone (GnRH), an estrogen-sensitive endpoint, was measured during GnRH challenge tests administered before, during and after dietary soy consumption. The response to an isoflavone-rich soy food diet was examined in five premenopausal and seven postmenopausal women using transdermal estrogen replacement therapy. Estrogen agonists suppress gonadotropin concentrations and enhance GnRH priming (enhanced gonadotropin secretion in response to repeated doses of GnRH), whereas antagonists elevate gonadotropin concentrations and have no effect on GnRH priming. Each subject consumed 50 g textured soy protein containing 60 mg total isoflavones daily for 10-14 d. Baseline estradiol concentrations were consistent among study periods. In both pre- and postmenopausal women, soy consumption did not affect mean baseline or peak luteinizing hormone (LH) concentrations, indicating a lack of estrogen-like effect at the level of the pituitary. However, in postmenopausal subjects, mean LH secretion decreased after discontinuing soy, suggesting a residual estrogenic effect. In one premenopausal woman, enhanced LH secretion was observed after soy treatment, suggesting there may be subpopulations of women who are highly sensitive to isoflavones.

Adult↗

PubMed2002

The relationship of circulating dehydroepiandrosterone, testosterone, and estradiol to stages of the menopausal transition and ethnicity.

In this report, 3029 women between the ages of 42 and 54 yr from five ethnic groups were studied for 2 yr. Log circulating dehydroepiandrosterone sulfate (DHEAS) concentrations were highest among Chinese and Japanese and lowest among African Americans and Hispanics, and this pattern persisted after adjustment for age, smoking, and log body mass index (BMI). With the exception of Japanese women, log BMI was negatively related to log circulating DHEAS. The magnitude of this association varied by ethnic group, and the decline in log circulating DHEAS levels with higher log BMI was steepest for Chinese and least steep for Hispanics. The relationship between log DHEAS and log BMI was positive for Japanese. DHEAS levels did not decline at a steady rate during the menopausal transition and transiently increased in some women and increased, on average, during the transition to late perimenopause. These increases tended to be larger for Chinese, Hispanic, and Japanese than for African Americans and Caucasians, although the interactions were not statistically significant. Changes in circulating testosterone and, to a lesser extent, estradiol were correlated to changes in DHEAS. These data have importance in understanding the endocrinology of the menopausal transition, defining the relationship of adrenal steroid production during declining ovarian function and determining a rationale regarding DHEAS supplementation for older women.

Adult↗

PubMed2002

Detection of xenoestrogens in serum after immunoprecipitation of endogenous steroidal estrogens.

In this article we report a simple and efficient method for detecting nonsteroidal estrogens in a biologic sample. This method uses polyclonal antibodies to estradiol (E2) to immunoprecipitate these major biologically active steroidal estrogens, leaving behind the nonsteroidal estrogens, which are then detected in a cell-based transcriptional activation bioassay for estrogen receptor agonist. The immunoprecipitation method efficiently removed 99% of radiolabeled E2 and estrone (E1) from human serum. In experiments in which supraphysiologic concentrations of E2 and E1 to human serum, all of the immunoreactive estrogens were still removed by the immunoprecipitation protocol. We carried out an in vivo validation study of this method in which we treated female macaques with the xenoestrogen nonylphenol (NP), during the late follicular phase of the menstrual cycle. We used blood samples collected before and after treatment to evaluate and characterize endogenous and exogenous serum estrogens. An immunoassay for E2 did not detect the NP in treated monkeys. The cell-based bioassay also did not detect the estrogenic activity of NP because of its saturation by the endogenous serum steroidal estrogens. However, when steroidal estrogens were removed by immunoprecipitation, we detected the estrogenic activity of NP in the bioassay. Thus, this approach is appropriate for detecting exogenous, nonsteroidal estrogens in serum samples.

Animals↗

PubMedDate not supplied

Mild testicular hyperthermia induces profound transitional spermatogenic suppression through increased germ cell apoptosis in adult cynomolgus monkeys (Macaca fascicularis).

We have previously demonstrated that mild testicular hyperthermia induces stage-specific and germ cell-specific apoptosis in rat and mouse testes. The objectives of this pilot study were to examine whether mild testicular hyperthermia induces azoospermia and oligozoospermia in nonhuman primates, and to determine whether spermatogenesis suppression was due to acceleration of germ cell apoptosis. Three adult Cynomolgus monkeys (Macaca fascicularis) were used in this study. The scrota containing the testes were immersed in a water bath at 43 degrees C for 30 minutes once daily for 6 consecutive days. Semen and blood samples were collected at 2 and 1 weeks before, and 2, 4, 6, 8, 10, and 12 weeks after the first heat treatment. Testicular biopsies were performed before and at 3 and 7 days, and 12 weeks after the first heat exposure. Apoptosis in testicular biopsy was assessed by TUNEL assay, by electron microscopy, and by detection of cleaved Poly(ADP-ribose)polymerase with Western blotting. A transient decrease in serum testosterone levels was observed in 2 monkeys 2 weeks after heat treatment. Serum inhibin B levels declined in all 3 monkeys 2 weeks after testicular hyperthermia and remained at relatively low levels throughout the study in 2 of 3 monkeys. Two of 3 monkeys exhibited azoospermia by 6 or 8 weeks after the first heat treatment; the remaining monkey had marked oligozoospermia (8 x 10(6)/ejaculate, 10.89% of pretreatment levels) 6 weeks after the first heat treatment. Increased germ cell apoptosis in testicular biopsy samples was found at 3 and 7 days after the first heat exposure. Using immunohistochemistry, we observed that the immunoactivity of proapoptotic Bax protein accumulated in heat-induced apoptotic germ cells. Full recovery of spermatogenesis was noted 12 weeks after the first heat treatment. We conclude that, similar to rodents, mild testicular hyperthermia results in azoospermia and oligozoospermia in monkeys through increased germ cell apoptosis with minimal effect on the hormonal milieu.

Animals↗