The phenomenon of musth is a very stressful event, both behaviorally and physiologically. An ACTH... more The phenomenon of musth is a very stressful event, both behaviorally and physiologically. An ACTH stimulation test was conducted in four adult Asian bull elephants to investigate the possibility that the classical hypothalamic-pituitary-adrenal (HPA) axis is active during musth, resulting in an increase in adrenally produced steroids. Serum cortisol, testosterone (T), androstenedione (A4), androstenediol (A5), and dehydroepiandrosterone (DHEA) were measured. Cortisol increased 3-10 times above baseline in response to ACTH stimulation, and DHEA doubled. A4 and A5 were erratic, while testosterone decreased significantly in all bulls. The pattern of results suggests that the adrenal steroid increase which occurs during musth results from some mechanism other than the classical HPA axis.
The Journal of Clinical Endocrinology & Metabolism, 2005
Context: Androgens influence sexual differentiation and behavior, body composition, and physical ... more Context: Androgens influence sexual differentiation and behavior, body composition, and physical functioning in men, but their role in women is less well understood. Because circulating androgens decline with age, the use of androgen supplementation for women to improve health and well-being has been increasing. Objective: The aim of this study was to assess the association between androgens and a variety of end points thought to be affected by androgens. Design: In a community-based baseline cohort of women aged 42-52 yr from the Study of Women's Health Across the Nation, we measured circulating testosterone (T), dehydroepiandrosterone sulfate, and SHBG, and calculated a free androgen index (FAI) in 2961 women. Main Outcome Measures: Correlations of androgen measures with each other and with body mass index, waist circumference, and waisthip ratio were computed, and odds ratios (OR) were estimated for the categorical outcomes of functional limitations, functional status, selfreported health, scores indicative of depressed mood, quality of life, sexual desire and arousal, and the presence of the metabolic syndrome. Results: Androgens, and particularly SHBG, were associated most strongly with body mass index, waist circumference, and waist-hip ratio. SHBG was associated prominently inversely with the metabolic syndrome (OR ϭ 0.32; 95% confidence interval ϭ 0.26-0.39), which was present in 17% of women at baseline. Dehydroepiandrosterone sulfate was associated modestly with functional status and self-reported health. T was associated minimally with increased sexual desire (OR ϭ 1.09; 95% confidence interval ϭ 1.00-1.18). The association of FAI with self-reported health and depressive symptomatology based on the Center for Epidemiologic Studies Depression Scale score was explained more by T than by SHBG, whereas the association of FAI with sexual arousal and metabolic syndrome was due more to SHBG than to T. Conclusions: Circulating SHBG and androgens are most strongly associated with physical characteristics and the metabolic syndrome in women in this community-based cohort. Androgens are related weakly to physical functioning and other symptoms to which they commonly are attributed, such as sexual desire, sexual arousal, and well-being.
The Journal of clinical endocrinology and metabolism, Jul 22, 2017
Menstrual cycle hormone patterns in women approaching menopause are inadequately studied. To desc... more Menstrual cycle hormone patterns in women approaching menopause are inadequately studied. To describe day-to-day menstrual cycle hormones in women as they approach menopause from the Study of Women's Health Across the Nation (SWAN) Daily Hormone Study (DHS). DHS enrollees collected daily urine for one entire menstrual cycle or up to 50 days, whichever came first, annually, up to the final menstrual period (FMP) or for up to 10 years. 7 sites across the US. 511 premenopausal or early perimenopausal women at enrollment, within 10 years before menopause. time-to-FMP measurement. Evidence of luteal activity (ELA), determined using objective algorithms. Menstrual cycle/segment length; whole cycle and segment integrated urinary LH, FSH, estrone conjugates (E1c) and pregnanediol glucuronide (Pdg) for each year, organized around the FMP. Mean menstrual cycle length was remarkably preserved at 26-27 days in ELA cycles; non-ELA cycles had greater variability. The % cycles that were ELA re...
The phenomenon of musth is a very stressful event, both behaviorally and physiologically. An ACTH... more The phenomenon of musth is a very stressful event, both behaviorally and physiologically. An ACTH stimulation test was conducted in four adult Asian bull elephants to investigate the possibility that the classical hypothalamic-pituitary-adrenal (HPA) axis is active during musth, resulting in an increase in adrenally produced steroids. Serum cortisol, testosterone (T), androstenedione (A4), androstenediol (A5), and dehydroepiandrosterone (DHEA) were measured. Cortisol increased 3-10 times above baseline in response to ACTH stimulation, and DHEA doubled. A4 and A5 were erratic, while testosterone decreased significantly in all bulls. The pattern of results suggests that the adrenal steroid increase which occurs during musth results from some mechanism other than the classical HPA axis.
Smoking, diet and physical activity may impact chronic diseases, in part, by promoting or attenua... more Smoking, diet and physical activity may impact chronic diseases, in part, by promoting or attenuating oxidative stress. We evaluated associations between lifestyle factors and urine F 2a-isoprostanes, a marker of oxidative stress among 1610 participants of Study of Women's Health Across the Nation (SWAN). Dietary intake and physical activity were assessed at baseline and year 05 (Y05). These data were related to Y05 urinary F 2a-isoprostane concentration with regression analyses. Median urine F 2a-isoprostane concentration was 433 ng/L overall, 917 ng/L in smokers (inter-quartile range: 467, 1832 ng/L) and 403 ng/L in non-smokers (inter-quartile range: 228, 709 ng/L; P<0.0001 for difference). Higher trans fat intake was associated with higher urine F 2a-isoprostane concentration; partial Spearman correlations (ρ x|y) between Y05 urine F 2a-isoprostane concentration and trans fatty acids were 0.19 (P=0.03) and 0.13 (P <0.0001) in smokers and non-smokers, respectively. Increased log trans fat intake from baseline to Y05 was associated with higher concentration of logurine F 2a-isoprostanes in non-smokers (β=0.131, SE=0.04, P =0.0003). In non-smokers, the partial correlation (ρ x|y) between lutein and urine F 2a-isoprostane concentration was −0.13 (P <0.0001). Increased intake of log lutein from baseline to Y05 was also associated with lower log urine F 2a-isoprostane concentration (β= −0.096, SE=0.03, P =0.0005) in non-smokers. Increased zinc intake from baseline to Y05 was associated with lower log urine F 2a-isoprostane concentration in smokers and non-smokers (β= −0.346, SE=0.14, P =0.01), and −0.117, 0.04 (P =0.001), respectively]. In conclusion, diet (fat subtypes, zinc, vegetable components) and smoking were associated with urine F 2a-isoprostanes, a marker of oxidative stress.
Background: It has been speculated that gender differences in car- diovascular disease (CVD) mort... more Background: It has been speculated that gender differences in car- diovascular disease (CVD) mortality can be attributed to the effects of estrogens on inflammation and hemostatic marker profiles. There- fore, we evaluated endogenous hormone concentrations, menopause transition stages, and adoption of exogenous hormone use in relation to hemostatic and inflammation marker concentrations in women. Methods: Longitudinally, we studied 3302 participants
Goal: The goal of this study was to relate annually measured en- dogenous androgens to hemostatic... more Goal: The goal of this study was to relate annually measured en- dogenous androgens to hemostatic and inflammation markers in women longitudinally. Methods:Atotalof3302participantsfromtheStudyofWomen'sHealth Across the Nation, aged 42-52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%) were evaluated for testosterone (T), dehydroepiandro- sterone sulfate, and SHBG at four time points in
It is well documented that estrogen increases dendritic spine density in CA1 pyramidal cells of y... more It is well documented that estrogen increases dendritic spine density in CA1 pyramidal cells of young female rats. However, this effect is attenuated in aged rats. We report here a quantitative analysis of estrogen effects on hippocampal spine number as visualized with antispinophilin in young (6-8 years old) and aged (19-23 years old) female rhesus monkeys, a species with a pattern of female endocrine senescence comparable to that of humans. Monkeys were ovariectomized and administered either vehicle or estradiol cypionate 3 months postovariectomy, followed by an additional dose 3 weeks later, with perfusion 24 hours after the last estrogen treatment. Immunolocalization of spinophilin, a spine-associated protein, was used for quantitative stereologic analyses of total spinophilin-immunoreactive spine numbers in CA1 stratum radiatum and the inner and outer molecular layers of dentate gyrus. In both young and aged female monkeys, the estrogen-treated groups had an increase in spinoph...
Female green iguanas, Iguana iguana, were caught in Belize, Central America (17"N), in December, ... more Female green iguanas, Iguana iguana, were caught in Belize, Central America (17"N), in December, at the onset of seasonal gonadal activity. The animals were immediately transferred to San Diego (32"N). Ovarian follicular development continued, with peak plasma hormone levels measured in January and February; 200 pg/ml for progesterone (P) and 800 pg/ml for
Reliable and safe methods of reversible contraception are needed for use in zoo felids. The effic... more Reliable and safe methods of reversible contraception are needed for use in zoo felids. The efficacy of levonorgestrel (LNG) as a contraceptive, when delivered as a cesium-irradiated, slow-release, injectable matrix, was tested in domestic cats as a model for exotic cats. An increase (P = 0.0017) in body weight was observed in treated but not control queens (P = 0.2146). All control queens (n = 6), which received injections of matrix only, but none of the LNG-treated queens (n = 6) became pregnant during the trial. Levonorgestrel was effective in preventing pregnancy for at least 36 weeks after two injections of drug-loaded formulations (40 mg/kg body weight), administered 68 days apart. Throughout the study, all control queens displayed luteal activity and fluctuating fecal estradiol concentrations, whereas the LNG-treated queens displayed lower estradiol concentrations and no luteal activity after treatment. We conclude that LNG, when delivered as a cesium-irradiated, slow-release, injectable matrix, is an effective contraceptive in domestic cats, reducing follicular activity, and thus, preventing mating and luteal activity. Zoo Biol 20: 407-421, 2001.
Concerns have been raised about the biological and toxicologic effects of the antimicrobials tric... more Concerns have been raised about the biological and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. Few studies have evaluated their biological activities in mammalian cells to assess their potential for adverse effects. OBJECTIVES: In this study, we assessed the activity of TCC, its analogs, and TCS in in vitro nuclear-receptor-responsive and calcium signaling bioassays. MATERIALS AND METHODS: We determined the biological activities of the compounds in in vitro, cell-based, and nuclear-receptor-responsive bioassays for receptors for aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), and ryanodine (RyR1).
Context: It is important to characterize the biological activity of circulatingandrogenicsteroidh... more Context: It is important to characterize the biological activity of circulatingandrogenicsteroidhormonesduringthemenopausaltran- sition because these appear to impact the metabolic and cardiovas- cular health risk factors of women. Objective:The objective of the study was to develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum. Design: This was a clinically relevant experimental study nested in a
Abstract The purpose of this study was to assess the effects of Norplant implants on ovarian horm... more Abstract The purpose of this study was to assess the effects of Norplant implants on ovarian hormone secretion and genital swelling patterns in female chimpanzees. Urine samples were collected during one natural cycle before (n= 5 females) and one cycle∼ 6 months ...
Enzymeimmunoassays (EIAs) for estrone conjugates (EC), pregnanediol-3-glucuronide (PDG), and C-19... more Enzymeimmunoassays (EIAs) for estrone conjugates (EC), pregnanediol-3-glucuronide (PDG), and C-19 and C-21 progesterone metabolites (C-19/C-21) were used to analyze urine samples from four nondomestic equid species, four tapir species, and two rhinoceros species in an attempt to identify if these assays could be used for diagnosing and monitoring pregnancy. The same urine samples were also analyzed for the presence of equine chorionic gonadotropin (eCG) activity, using a field dipstick test and a radioimmunoassay (RIA). The EC EIA was validated for three equid species and the Malayan tapir. Neither the PDG nor the C-19K-21 EIAs were validated in any species evaluated. In equid species, the EC EIA demonstrated a specificity (the percentage of nonpregnant samples identified correctly) of 100% and a sensitivity (the percentage of pregnant samples identified correctly) of 288%. With the exception of the Grevy's zebra, the C-19K-21 EIA showed a similar accuracy in identifying pregnant and nonpregnant equids. The PDG EIA was not sufficiently accurate to merit its use in equids or tapirs for pregnancy diagnosis. From the data collected, it appears analysis of a single urine by both the EC EIA and the C-19/C-21 EIA would be the best method of pregnancy detection during the last 2 trimesters of gestation, in equid species. In tapirs, the C-19K-21 EIA was slightly more accurate for pregnancy diagnosis than the EC EIA. The C-19/C-21 EIA had a specificity of 93%, but a sensitivity of only 73% in tapir species. None of the EIAs evaluated demonstrated a sufficient specificity or sensitivity to be useful, as presently performed, for pregnancy diagnosis from a single sample in the black rhinoceros. The eCG dipstick used in this study did not prove a sufficiently reliable test for routine pregnancy in nondomestic equids. The eCG RIA results in the Przewalski's horses and the Hartman's mountain zebra were positive early in gestation, and indicate that gonadotropin analysis may be useful for pregnancy detection in these species. Only very low amounts of eCG activity was measured by the eCG RIA in the tapir and rhinoceros urine samples.
Histological features of adrenal glands from captive and unstressed free-ranging nine-banded arma... more Histological features of adrenal glands from captive and unstressed free-ranging nine-banded armadillos were compared to determine if undefined stress factors associated with captivity were capable of causing changes in adrenal morphology. Animals in captivity less than 3 mo showed histological features identical to unstressed free-ranging animals. Animals in captivity 6 mo or longer, however, showed adrenal changes like those previously described in other mammals exposed to various types of stress, except that there was no accompanying increase in adrenal weight. Similar adrenal changes were found in free-ranging animals exposed to extremely harsh winter weather. Females from both the chronic captive population and this stressed free-ranging population were seen to suffer reproductive failure. Reproductive function in males was not affected. There was no detectable sex difference in gross or histological adrenal changes; however, previous reports indicate there is a sex difference in the secretory product from the adrenals of captive nine-banded armadillos. A possible relationship between reproductive failure in the female and the sex difference in adrenal secretory products is discussed.
Different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1, 1, 5, and 10 g/kg body wt) we... more Different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1, 1, 5, and 10 g/kg body wt) were administered ip to 21-day-old male Sprague-Dawley rats. Control animals received the same volume of the vehicle (acetone:corn oil, 1:19). Body weight and daily food intake were recorded during the 90-day time course of the study. Random samples of five rats were sacrificed at 34, 49, 62, and 90 days of age. Epidermal growth factor receptor (EGFR) in whole testis was measured, as were the activities of c-Src kinase, protein tyrosine kinase (PTK), mitogen-activated protein 2 kinase (MAP2K also termed as Erk2), protein kinase A (PKA), and protein kinase C (PKC). Testicular tissue from 90-day-old rats was evaluated for histopathology, and sperm numbers in whole testis were counted to estimate daily sperm production. The motility of sperm in the vas deferens and caudal segments of the epididymis of 90-day-old rats was measured by computer assisted sperm analysis (CASA) and the function of the sperm was tested by assessment of acrosome reactions. A dose of 10 g/kg resulted in testicular atrophy and histopathologic examination revealed a decrease in the diameter of the seminiferous tubules. Sertoli cell nuclei were clearly seen, but the spermatogonial population was totally absent. Lower doses of TCDD did not affect testicular histology, but doses as low as 1 g/kg significantly decreased testicular sperm numbers and affected some sperm functions (motility parameters and acrosome reactions) in 90-day-old rats. Significant decreases in EGFR were found in 34-day-old rats and this effect on EGFR was sustained until the end of the experiment (90 days). Although TCDD significantly increased c-Src kinase activity in immature and mature rats, opposite effects of TCDD on activities of PTK, PKA, and PKC were found in 34-day-old rats vs 49-, 62-, and 90-day-old rats. When 10 g TCDD/kg was administered to 21-day-old rat, 24-h after c-Src kinase inhibitor geldanamycin, there was no testicular atrophy and no change in the daily sperm produc-tion was found. These findings provide evidence for involvement of Src kinase signaling and EGFR in the mechanism by which TCDD disrupts testicular development and subsequently affects testis function.
The phenomenon of musth is a very stressful event, both behaviorally and physiologically. An ACTH... more The phenomenon of musth is a very stressful event, both behaviorally and physiologically. An ACTH stimulation test was conducted in four adult Asian bull elephants to investigate the possibility that the classical hypothalamic-pituitary-adrenal (HPA) axis is active during musth, resulting in an increase in adrenally produced steroids. Serum cortisol, testosterone (T), androstenedione (A4), androstenediol (A5), and dehydroepiandrosterone (DHEA) were measured. Cortisol increased 3-10 times above baseline in response to ACTH stimulation, and DHEA doubled. A4 and A5 were erratic, while testosterone decreased significantly in all bulls. The pattern of results suggests that the adrenal steroid increase which occurs during musth results from some mechanism other than the classical HPA axis.
The Journal of Clinical Endocrinology & Metabolism, 2005
Context: Androgens influence sexual differentiation and behavior, body composition, and physical ... more Context: Androgens influence sexual differentiation and behavior, body composition, and physical functioning in men, but their role in women is less well understood. Because circulating androgens decline with age, the use of androgen supplementation for women to improve health and well-being has been increasing. Objective: The aim of this study was to assess the association between androgens and a variety of end points thought to be affected by androgens. Design: In a community-based baseline cohort of women aged 42-52 yr from the Study of Women's Health Across the Nation, we measured circulating testosterone (T), dehydroepiandrosterone sulfate, and SHBG, and calculated a free androgen index (FAI) in 2961 women. Main Outcome Measures: Correlations of androgen measures with each other and with body mass index, waist circumference, and waisthip ratio were computed, and odds ratios (OR) were estimated for the categorical outcomes of functional limitations, functional status, selfreported health, scores indicative of depressed mood, quality of life, sexual desire and arousal, and the presence of the metabolic syndrome. Results: Androgens, and particularly SHBG, were associated most strongly with body mass index, waist circumference, and waist-hip ratio. SHBG was associated prominently inversely with the metabolic syndrome (OR ϭ 0.32; 95% confidence interval ϭ 0.26-0.39), which was present in 17% of women at baseline. Dehydroepiandrosterone sulfate was associated modestly with functional status and self-reported health. T was associated minimally with increased sexual desire (OR ϭ 1.09; 95% confidence interval ϭ 1.00-1.18). The association of FAI with self-reported health and depressive symptomatology based on the Center for Epidemiologic Studies Depression Scale score was explained more by T than by SHBG, whereas the association of FAI with sexual arousal and metabolic syndrome was due more to SHBG than to T. Conclusions: Circulating SHBG and androgens are most strongly associated with physical characteristics and the metabolic syndrome in women in this community-based cohort. Androgens are related weakly to physical functioning and other symptoms to which they commonly are attributed, such as sexual desire, sexual arousal, and well-being.
The Journal of clinical endocrinology and metabolism, Jul 22, 2017
Menstrual cycle hormone patterns in women approaching menopause are inadequately studied. To desc... more Menstrual cycle hormone patterns in women approaching menopause are inadequately studied. To describe day-to-day menstrual cycle hormones in women as they approach menopause from the Study of Women's Health Across the Nation (SWAN) Daily Hormone Study (DHS). DHS enrollees collected daily urine for one entire menstrual cycle or up to 50 days, whichever came first, annually, up to the final menstrual period (FMP) or for up to 10 years. 7 sites across the US. 511 premenopausal or early perimenopausal women at enrollment, within 10 years before menopause. time-to-FMP measurement. Evidence of luteal activity (ELA), determined using objective algorithms. Menstrual cycle/segment length; whole cycle and segment integrated urinary LH, FSH, estrone conjugates (E1c) and pregnanediol glucuronide (Pdg) for each year, organized around the FMP. Mean menstrual cycle length was remarkably preserved at 26-27 days in ELA cycles; non-ELA cycles had greater variability. The % cycles that were ELA re...
The phenomenon of musth is a very stressful event, both behaviorally and physiologically. An ACTH... more The phenomenon of musth is a very stressful event, both behaviorally and physiologically. An ACTH stimulation test was conducted in four adult Asian bull elephants to investigate the possibility that the classical hypothalamic-pituitary-adrenal (HPA) axis is active during musth, resulting in an increase in adrenally produced steroids. Serum cortisol, testosterone (T), androstenedione (A4), androstenediol (A5), and dehydroepiandrosterone (DHEA) were measured. Cortisol increased 3-10 times above baseline in response to ACTH stimulation, and DHEA doubled. A4 and A5 were erratic, while testosterone decreased significantly in all bulls. The pattern of results suggests that the adrenal steroid increase which occurs during musth results from some mechanism other than the classical HPA axis.
Smoking, diet and physical activity may impact chronic diseases, in part, by promoting or attenua... more Smoking, diet and physical activity may impact chronic diseases, in part, by promoting or attenuating oxidative stress. We evaluated associations between lifestyle factors and urine F 2a-isoprostanes, a marker of oxidative stress among 1610 participants of Study of Women's Health Across the Nation (SWAN). Dietary intake and physical activity were assessed at baseline and year 05 (Y05). These data were related to Y05 urinary F 2a-isoprostane concentration with regression analyses. Median urine F 2a-isoprostane concentration was 433 ng/L overall, 917 ng/L in smokers (inter-quartile range: 467, 1832 ng/L) and 403 ng/L in non-smokers (inter-quartile range: 228, 709 ng/L; P<0.0001 for difference). Higher trans fat intake was associated with higher urine F 2a-isoprostane concentration; partial Spearman correlations (ρ x|y) between Y05 urine F 2a-isoprostane concentration and trans fatty acids were 0.19 (P=0.03) and 0.13 (P <0.0001) in smokers and non-smokers, respectively. Increased log trans fat intake from baseline to Y05 was associated with higher concentration of logurine F 2a-isoprostanes in non-smokers (β=0.131, SE=0.04, P =0.0003). In non-smokers, the partial correlation (ρ x|y) between lutein and urine F 2a-isoprostane concentration was −0.13 (P <0.0001). Increased intake of log lutein from baseline to Y05 was also associated with lower log urine F 2a-isoprostane concentration (β= −0.096, SE=0.03, P =0.0005) in non-smokers. Increased zinc intake from baseline to Y05 was associated with lower log urine F 2a-isoprostane concentration in smokers and non-smokers (β= −0.346, SE=0.14, P =0.01), and −0.117, 0.04 (P =0.001), respectively]. In conclusion, diet (fat subtypes, zinc, vegetable components) and smoking were associated with urine F 2a-isoprostanes, a marker of oxidative stress.
Background: It has been speculated that gender differences in car- diovascular disease (CVD) mort... more Background: It has been speculated that gender differences in car- diovascular disease (CVD) mortality can be attributed to the effects of estrogens on inflammation and hemostatic marker profiles. There- fore, we evaluated endogenous hormone concentrations, menopause transition stages, and adoption of exogenous hormone use in relation to hemostatic and inflammation marker concentrations in women. Methods: Longitudinally, we studied 3302 participants
Goal: The goal of this study was to relate annually measured en- dogenous androgens to hemostatic... more Goal: The goal of this study was to relate annually measured en- dogenous androgens to hemostatic and inflammation markers in women longitudinally. Methods:Atotalof3302participantsfromtheStudyofWomen'sHealth Across the Nation, aged 42-52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%) were evaluated for testosterone (T), dehydroepiandro- sterone sulfate, and SHBG at four time points in
It is well documented that estrogen increases dendritic spine density in CA1 pyramidal cells of y... more It is well documented that estrogen increases dendritic spine density in CA1 pyramidal cells of young female rats. However, this effect is attenuated in aged rats. We report here a quantitative analysis of estrogen effects on hippocampal spine number as visualized with antispinophilin in young (6-8 years old) and aged (19-23 years old) female rhesus monkeys, a species with a pattern of female endocrine senescence comparable to that of humans. Monkeys were ovariectomized and administered either vehicle or estradiol cypionate 3 months postovariectomy, followed by an additional dose 3 weeks later, with perfusion 24 hours after the last estrogen treatment. Immunolocalization of spinophilin, a spine-associated protein, was used for quantitative stereologic analyses of total spinophilin-immunoreactive spine numbers in CA1 stratum radiatum and the inner and outer molecular layers of dentate gyrus. In both young and aged female monkeys, the estrogen-treated groups had an increase in spinoph...
Female green iguanas, Iguana iguana, were caught in Belize, Central America (17"N), in December, ... more Female green iguanas, Iguana iguana, were caught in Belize, Central America (17"N), in December, at the onset of seasonal gonadal activity. The animals were immediately transferred to San Diego (32"N). Ovarian follicular development continued, with peak plasma hormone levels measured in January and February; 200 pg/ml for progesterone (P) and 800 pg/ml for
Reliable and safe methods of reversible contraception are needed for use in zoo felids. The effic... more Reliable and safe methods of reversible contraception are needed for use in zoo felids. The efficacy of levonorgestrel (LNG) as a contraceptive, when delivered as a cesium-irradiated, slow-release, injectable matrix, was tested in domestic cats as a model for exotic cats. An increase (P = 0.0017) in body weight was observed in treated but not control queens (P = 0.2146). All control queens (n = 6), which received injections of matrix only, but none of the LNG-treated queens (n = 6) became pregnant during the trial. Levonorgestrel was effective in preventing pregnancy for at least 36 weeks after two injections of drug-loaded formulations (40 mg/kg body weight), administered 68 days apart. Throughout the study, all control queens displayed luteal activity and fluctuating fecal estradiol concentrations, whereas the LNG-treated queens displayed lower estradiol concentrations and no luteal activity after treatment. We conclude that LNG, when delivered as a cesium-irradiated, slow-release, injectable matrix, is an effective contraceptive in domestic cats, reducing follicular activity, and thus, preventing mating and luteal activity. Zoo Biol 20: 407-421, 2001.
Concerns have been raised about the biological and toxicologic effects of the antimicrobials tric... more Concerns have been raised about the biological and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. Few studies have evaluated their biological activities in mammalian cells to assess their potential for adverse effects. OBJECTIVES: In this study, we assessed the activity of TCC, its analogs, and TCS in in vitro nuclear-receptor-responsive and calcium signaling bioassays. MATERIALS AND METHODS: We determined the biological activities of the compounds in in vitro, cell-based, and nuclear-receptor-responsive bioassays for receptors for aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), and ryanodine (RyR1).
Context: It is important to characterize the biological activity of circulatingandrogenicsteroidh... more Context: It is important to characterize the biological activity of circulatingandrogenicsteroidhormonesduringthemenopausaltran- sition because these appear to impact the metabolic and cardiovas- cular health risk factors of women. Objective:The objective of the study was to develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum. Design: This was a clinically relevant experimental study nested in a
Abstract The purpose of this study was to assess the effects of Norplant implants on ovarian horm... more Abstract The purpose of this study was to assess the effects of Norplant implants on ovarian hormone secretion and genital swelling patterns in female chimpanzees. Urine samples were collected during one natural cycle before (n= 5 females) and one cycle∼ 6 months ...
Enzymeimmunoassays (EIAs) for estrone conjugates (EC), pregnanediol-3-glucuronide (PDG), and C-19... more Enzymeimmunoassays (EIAs) for estrone conjugates (EC), pregnanediol-3-glucuronide (PDG), and C-19 and C-21 progesterone metabolites (C-19/C-21) were used to analyze urine samples from four nondomestic equid species, four tapir species, and two rhinoceros species in an attempt to identify if these assays could be used for diagnosing and monitoring pregnancy. The same urine samples were also analyzed for the presence of equine chorionic gonadotropin (eCG) activity, using a field dipstick test and a radioimmunoassay (RIA). The EC EIA was validated for three equid species and the Malayan tapir. Neither the PDG nor the C-19K-21 EIAs were validated in any species evaluated. In equid species, the EC EIA demonstrated a specificity (the percentage of nonpregnant samples identified correctly) of 100% and a sensitivity (the percentage of pregnant samples identified correctly) of 288%. With the exception of the Grevy's zebra, the C-19K-21 EIA showed a similar accuracy in identifying pregnant and nonpregnant equids. The PDG EIA was not sufficiently accurate to merit its use in equids or tapirs for pregnancy diagnosis. From the data collected, it appears analysis of a single urine by both the EC EIA and the C-19/C-21 EIA would be the best method of pregnancy detection during the last 2 trimesters of gestation, in equid species. In tapirs, the C-19K-21 EIA was slightly more accurate for pregnancy diagnosis than the EC EIA. The C-19/C-21 EIA had a specificity of 93%, but a sensitivity of only 73% in tapir species. None of the EIAs evaluated demonstrated a sufficient specificity or sensitivity to be useful, as presently performed, for pregnancy diagnosis from a single sample in the black rhinoceros. The eCG dipstick used in this study did not prove a sufficiently reliable test for routine pregnancy in nondomestic equids. The eCG RIA results in the Przewalski's horses and the Hartman's mountain zebra were positive early in gestation, and indicate that gonadotropin analysis may be useful for pregnancy detection in these species. Only very low amounts of eCG activity was measured by the eCG RIA in the tapir and rhinoceros urine samples.
Histological features of adrenal glands from captive and unstressed free-ranging nine-banded arma... more Histological features of adrenal glands from captive and unstressed free-ranging nine-banded armadillos were compared to determine if undefined stress factors associated with captivity were capable of causing changes in adrenal morphology. Animals in captivity less than 3 mo showed histological features identical to unstressed free-ranging animals. Animals in captivity 6 mo or longer, however, showed adrenal changes like those previously described in other mammals exposed to various types of stress, except that there was no accompanying increase in adrenal weight. Similar adrenal changes were found in free-ranging animals exposed to extremely harsh winter weather. Females from both the chronic captive population and this stressed free-ranging population were seen to suffer reproductive failure. Reproductive function in males was not affected. There was no detectable sex difference in gross or histological adrenal changes; however, previous reports indicate there is a sex difference in the secretory product from the adrenals of captive nine-banded armadillos. A possible relationship between reproductive failure in the female and the sex difference in adrenal secretory products is discussed.
Different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1, 1, 5, and 10 g/kg body wt) we... more Different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1, 1, 5, and 10 g/kg body wt) were administered ip to 21-day-old male Sprague-Dawley rats. Control animals received the same volume of the vehicle (acetone:corn oil, 1:19). Body weight and daily food intake were recorded during the 90-day time course of the study. Random samples of five rats were sacrificed at 34, 49, 62, and 90 days of age. Epidermal growth factor receptor (EGFR) in whole testis was measured, as were the activities of c-Src kinase, protein tyrosine kinase (PTK), mitogen-activated protein 2 kinase (MAP2K also termed as Erk2), protein kinase A (PKA), and protein kinase C (PKC). Testicular tissue from 90-day-old rats was evaluated for histopathology, and sperm numbers in whole testis were counted to estimate daily sperm production. The motility of sperm in the vas deferens and caudal segments of the epididymis of 90-day-old rats was measured by computer assisted sperm analysis (CASA) and the function of the sperm was tested by assessment of acrosome reactions. A dose of 10 g/kg resulted in testicular atrophy and histopathologic examination revealed a decrease in the diameter of the seminiferous tubules. Sertoli cell nuclei were clearly seen, but the spermatogonial population was totally absent. Lower doses of TCDD did not affect testicular histology, but doses as low as 1 g/kg significantly decreased testicular sperm numbers and affected some sperm functions (motility parameters and acrosome reactions) in 90-day-old rats. Significant decreases in EGFR were found in 34-day-old rats and this effect on EGFR was sustained until the end of the experiment (90 days). Although TCDD significantly increased c-Src kinase activity in immature and mature rats, opposite effects of TCDD on activities of PTK, PKA, and PKC were found in 34-day-old rats vs 49-, 62-, and 90-day-old rats. When 10 g TCDD/kg was administered to 21-day-old rat, 24-h after c-Src kinase inhibitor geldanamycin, there was no testicular atrophy and no change in the daily sperm produc-tion was found. These findings provide evidence for involvement of Src kinase signaling and EGFR in the mechanism by which TCDD disrupts testicular development and subsequently affects testis function.
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