Biomedical subjects

V Daniel Castracane

Publications and source records attributed to V Daniel Castracane.

11 recordsLinked to original sources

PubMed2003

Variability of serum estrogens among postmenopausal women treated with the same transdermal estrogen therapy and the effect on androgens and sex hormone binding globulin.

OBJECTIVE: To examine the variability of serum estrogens in response to transdermal estrogen replacement therapy (ET), and to determine the effects on androgens and sex hormone binding globulin (SHBG). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Women's hospital. PATIENT(S): Two groups of postmenopausal women: [1] 21 women not on ET enrolled and 17 completed the study; [2] 19 women on continuous transdermal ET enrolled and 13 completed the study. INTERVENTION(S): Women not on ET were administered a placebo patch or a newly initiated estrogen patch, then crossed over to the alternate treatment. Serum samples were obtained at baseline and the subsequent 3 days from the placebo and new-patch groups and from a separate group of women receiving continuous estrogen patch treatment. MAIN OUTCOME MEASURE(S): Estradiol (E(2)), estrone, estrone sulfate, T, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, free androgen index, and SHBG. RESULT(S): There was considerable intrapatient and interpatient variability in the estrogen response to identical treatment doses, with E(2) values differing between women as much as 138 pg/mL and E(2) increases above baseline differing as much as 90 pg/mL. Continuous treatment increased SHBG and decreased androstenedione levels; however, levels of T, DHEA, DHEAS, and free androgen index did not change. CONCLUSION(S): There is great variability of estrogen in response to transdermal ET, but minimal effect on circulating androgens.

Administration, Cutaneous↗

PubMed2003

Premature ovarian failure associated with autoimmune polyglandular syndrome: pathophysiological mechanisms and future fertility.

BACKGROUND: Autoimmune polyglandular syndromes (APS) are a series of disorders characterized by autoimmunity against two or more endocrine organs. Premature ovarian failure (POF) may also have an autoimmune origin and, when accompanied by other autoimmune endocrinopathies, may be part of the APSs. Onset of autoimmune ovarian failure usually occurs in childhood, adolescence, or adulthood, and as a result, fertility may be severely compromised. CASE REPORT: A 26-year-old women with secondary amenorrhea, Addison's disease, and autoimmune hypothyroidism requested infertility evaluation. Examination, transvaginal ultrasonography, endocrine evaluation, and ovarian biopsy were performed. 21-Hydroxylase and antithyroid antibodies were demonstrated, but ovarian steroid cell antibodies (StCA) were absent at the time of her infertility evaluation. Transvaginal sonography demonstrated only a few ovarian follicles. An ovarian biopsy revealed lymphocytic infiltration of the ovary. This presentation is consistent with APS type II accompanied by autoimmune POF. DISCUSSION: Unlike APS types I and III, autoimmune POF is more commonly encountered with APS types I and III than with APS type II. An autoimmune response to steroidogenic enzymes and ovarian steroid cells appears to mediate destruction of ovarian function. Although immunotherapy with corticosteroids (with or without in vitro fertilization [IVF]) may be successful in limited cases where several follicles are present, oocyte donation with IVF may be the best option for the patient seeking fertility, particularly in the absence of ovarian follicles. CONCLUSIONS: Advances in molecular genetics may be valuable in predicting and counseling women at risk for APS and POF, and cryopreservation of ovarian tissue may offer hope to affected unmarried young women. It is reasonable to suggest that children and reproductive aged women with one autoimmune disorder should be periodically screened for other autoimmune disorders.

Adult↗

PubMed2003

Changes in circulating leptin, leptin receptor, and gonadal hormones from infancy until advanced age in humans.

We determined developmental changes in circulating levels of the soluble leptin receptor (sOB-R), leptin, and gonadal hormones in human subjects. In both sexes the rise in leptin with age was associated with a decline in sOB-R, and age-related changes in both parameters preceded the pubertal rise in gonadal hormones. Leptin levels above 10 ng/ml were a strong predictor of sOB-R concentrations, but this predictive value decreased as leptin declined. In young subjects there were no gender differences in serum leptin, but boys had higher sOB-R levels. In adults neither leptin nor sOB-R changed with age, but serum leptin was higher and sOB-R was lower in women than men. There was a significant negative correlation between sOB-R and leptin in women, but not men. The data suggest that bioavailable leptin in the circulation may be increasing more rapidly during development than indicated by total leptin levels, and that these changes may serve as one of the signals to the central nervous system that metabolic conditions are adequate to support pubertal development. Furthermore, the study provides suggestive evidence that leptin regulates the secretion of its own binding protein, but it also appears that an additional gender-specific, leptin-independent, regulatory mechanism is functional before puberty.

Adolescent↗

PubMed2003

Hormonal responses from concentric and eccentric muscle contractions.

UNLABELLED: Intense resistance exercise can acutely increase testosterone (T), free testosterone (FT), and growth hormone (GH) concentrations, but there are few investigations concerning acute endocrine responses to concentric (CON) and eccentric (ECC) contractile actions. PURPOSE: The purpose of the study was to compare acute anabolic hormonal responses to bouts of dynamic CON and ECC contractions from multiple exercises at the same absolute load. METHODS: Ten young men (age: 24.7 +/- 1.2 yr, weight: 85.45 +/- 24.2 kg, and height: 178 +/- 0.2 cm) completed two trials in counterbalanced fashion consisting of only CON or ECC contractions at the same absolute workload. Subjects performed four sets of 12 repetitions of bench press, leg extension, military press, and leg curl at 80% of a 10-repetition maximum with 90-s rest periods. Blood samples were collected pre-, post-, and 15-min postexercise. RESULTS: There were significant increases in GH, T, and FT and lactate for both trials, but only GH and lactate were greater for the CON trial. CONCLUSION: CON exercise increases GH concentrations to a much greater extent than ECC exercise at the same absolute load, and it is likely that greater GH responses were related to intensity rather than mode of contraction. Also, CON and ECC dynamic contraction trials at the same absolute workload elicited similar small but significant increases in T and FT, indicating that the greater metabolic stress produced by during the CON trial did not affect these hormone responses.

Adult↗

PubMed2003

RPE, pain, and physiological adjustment to concentric and eccentric contractions.

PURPOSE: The purpose of the study was to compare perceptual (RPE and pain), cardiac (heart rate), lactate, and endocrine (cortisol) responses with concentric (CON) and eccentric (ECC) resistance exercise protocols using the same absolute workload. METHODS: Eight healthy men with resistance-training experience participated in the study. Subjects completed two experimental trials consisting of either CON contractions or ECC contractions at the same absolute workload for each of four exercises: bench press, leg extension, military press, and leg curl. Subjects performed four sets of 12 repetitions at 80% of 10-RM with 90-s rest periods. Blood samples were taken before, immediately after, and 15-min postexercise. RESULTS: There was a significant trial effect for RPE, with CON exercise eliciting a higher RPE than ECC exercise (6.71 +/- 0.51 and 4.10 +/- 0.27, respectively). A significant trial effect was also demonstrated for pain, with CON exercise producing a higher pain rating than ECC exercise (5.59 +/- 0.41 and 3.23 +/- 0.27, respectively). Significantly higher heart rates and lactates were also demonstrated during the CON trial. For cortisol, a significant interaction was revealed between the pre- and immediate posttrial measures but not an overall trial effect. Correlational analyses revealed a significant relationship between RPE and pain for both trials. CONCLUSIONS: CON exercise elicits greater perceptual (higher RPE and pain rating), cardiac, lactate and cortisol response than ECC exercise at the same absolute workload. Data demonstrate that relative to absolute load, RPE and pain respond to resistance exercise in a similar fashion. Additionally, physiological cues are consistent with these perceptual data.

Adolescent↗

PubMed2003

Adiponectin responses to continuous and progressively intense intermittent exercise.

PURPOSE: Adiponectin is a recently discovered adipocyte protein that is lower in patients with coronary artery disease and in Type II diabetics who have insulin resistance. Regular exercise is known to be a preventative factor in the development of atherosclerosis and Type II diabetes. Acute exercise increases insulin sensitivity; however, it also increases beta-adrenergic and glucocorticoid activities that may suppress adiponectin expression. Two experiments were conducted to determine whether acute exercise affects adiponectin concentrations. METHODS: In the first experiment, six healthy male subjects completed 30 min of heavy continuous running exercise at 79% of VO (2max). In the second experiment, well-trained runners completed strenuous intermittent exercise consisting of treadmill running at 60, 75, 90, and 100% VO (2max). A resting control trial for the second experiment was also conducted. RESULTS: Glucose and insulin were not altered significantly in the first experiment, but both increased significantly (P < 0.05) in the second experiment. A significant increase (P < 0.05) in adiponectin in the first experiment was no longer significant after correction for plasma volumes shifts. In the second experiment, there were significant (P < 0.05) changes in adiponectin concentrations over time but not a significant difference between adiponectin responses in exercise and control trials. CONCLUSIONS: The data suggest that 30 min of heavy continuous running or more strenuous intermittent running does not stimulate an increase in production and release of adiponectin, and small increases in adiponectin concentrations resulting from the exercise may be attributed to normal plasma volume shifts.

Adiponectin↗

PubMed2002

Substrate utilization during exercise in postmenopausal women on hormone replacement therapy.

It has been suggested that due to the slight direct or indirect effect of estrogen on lipolytic activity, the age-related decrease in production associated with the menopause may heighten the risk of cardiovascular and metabolic disease in women. While hormone replacement therapy (HRT) alone may have little or no effect on body mass in postmenopausal women, data suggest it can alter the shift toward abdominal adiposity. Furthermore, estrogen may have a synergistic effect on exercise-induced reduction in fat mass. Accordingly, the purpose of this investigation was to examine the potential influence of HRT on substrate utilization during 30 min of treadmill exercise at approximately 80% maximal oxygen uptake (VO(2max)) in postmenopausal women. Eight women were receiving HRT and nine women were not (NHRT). No significant differences between the HRT and NHRT groups were noted for age, body mass, body fat, VO(2max) or the percentage of VO(2max) maintained during exercise. Expired gas samples were analyzed every 30 s to determine respiratory exchange ratio (R) and % VO(2max). The R, total energy expended and percentage contributions from fats and carbohydrate were averaged over three periods during the exercise (min 1-10, 11-20, and 21-30). There was no effect of HRT on R, total energy expended or substrate contribution. Thus, treatment of postmenopausal women using HRT (primarily conjugated equine estrogens in doses of 0.625-1.25 mg x day(-1)) did not appear to affect the percentages of fat and carbohydrate utilized during 30 min of treadmill exercise at 80% of VO(2max). However, the exercise responses in this group of menopausal women were consistent with a duration-dependent increased reliance on fat as an energy source during exercise of moderate to vigorous intensity as has been demonstrated in younger populations.

Aged↗

PubMed2002

When did leptin become a reproductive hormone?

Almost 50 years ago the obese mouse model was identified, and parabiosis studies were able to demonstrate that some humoral factor was involved in adiposity, so that the genetics and endocrine nature of this process have been apparent for many years. With the discovery of leptin just a few years ago, early studies validated the role of this protein product of the obese gene. Early studies in the obese mouse model ( ob/ob mouse) demonstrated that the genetic basis was truly a deficiency in leptin. Coincidentally, the relationship to fertility was also associated with leptin. These early studies were also able to demonstrate a relationship to puberty and the time of pubertal development. Very quickly, the recognition that the placenta was a source of leptin and that leptin levels were elevated in pregnancy in a number of species also broadened our appreciation of the relationship to reproductive functions. These many rapidly elucidated relationships to leptin were reported soon after the identification and availability of leptin as a research reagent and have firmly put leptin into the area of reproductive physiology in addition to establishing roles in metabolism, satiety, and energy metabolism. Subsequent studies have expanded all of these situations. Species beyond the rodent model, including the human, have now introduced these physiologic studies into the clinical arena and the role of leptin in fertility, puberty, pregnancy, and genetics. In this issue, all of these topics are reviewed to bring the reader up to date with leptin and its role in reproductive function, many of which overlap with the control of obesity.

Animals↗

PubMed2002

Leptin: roles and regulation in primate pregnancy.

Leptin, a hormone produced by adipose tissue and the placenta, is enhanced in the maternal circulation throughout pregnancy in both the human and the baboon ( Papio sp.), a proven nonhuman primate model for the study of human pregnancy. The presence of both leptin and its receptor in the fetus implies a role for the polypeptide as a regulator of in utero development, although localization in the placental trophoblast may relate to autocrine and/or paracrine regulatory functions in this important endocrine tissue. Although regulatory mechanisms remain incompletely defined, it has been suggested that cross talk occurs between the fetus, placenta, and maternal adipose stores. Placental estrogen, which is present in increasing concentrations with advancing gestation, is suggested to influence leptin synthesis in a tissue- and cell type-specific fashion. In this capacity, cellular hypoxia, diabetes, and preeclampsia are conditions that appear to be intimately linked to leptin dynamics. A better understanding of regulatory mechanisms will have direct clinical significance, as leptin has been proposed to impact on those causes of human perinatal morbidity and mortality that are associated with anomalies of fetal maturity and development, general conceptus growth, trophoblast endocrinology, and placental sufficiency.

Animals↗

PubMed2002

Polycystic ovarian syndrome and insulin resistance in white and Mexican American women: a comparison of two distinct populations.

OBJECTIVES: We sought to determine what differences, if any, existed between white and Mexican American women with polycystic ovary syndrome (PCOS) and whether the same values for fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment (HOMA) might be applied when screening both ethnic groups for insulin resistance. STUDY DESIGN: Eighty-three consecutive women suspected to have PCOS but who demonstrated absence of other endocrine disorders comprised the study population. Nineteen healthy ovulatory women volunteered as controls. Fasting serum samples were obtained for determination of thyroid-stimulating hormone (TSH), prolactin, glucose, insulin, free and total testosterone, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate in the early proliferative phase. An oral glucose load was administered, and blood samples for glucose and insulin were drawn at 1, 2, and 3 hours. Those with impaired glucose tolerance or diabetes mellitus were excluded from our final study population. Four different groups were defined: (1) women with PCOS and insulin resistance, (2) women with PCOS without insulin resistance, (3) women with irregular cycles but without PCOS or another identifiable endocrinopathy, and (4) regular, cycling control subjects. Each group was subdivided by ethnicity (white or Mexican American). A total of 65 white and 37 Mexican American women were studied, including control subjects. RESULTS: Among all study participants, Mexican American women with PCOS had significantly higher mean values for body mass index, fasting insulin, and HOMA but lower mean fasting glucose/insulin levels than white women. When group 1 patients (PCOS with insulin resistance) were compared between ethnic groups, mean fasting insulin and HOMA levels were significantly lower and glucose/insulin ratios higher in white than in Mexican American women. A single cutoff value for insulin resistance in PCOS was insensitive when applied to both ethnic groups. A fasting insulin value >20 microU/mL, HOMA value > 3.8, and glucose/insulin value <7.2 were reasonable screening values in our population of white women, whereas a fasting insulin value >23 microU/mL, HOMA value >4.5, and glucose/insulin ratio <4.0 were feasible screening values in Mexican American women. CONCLUSIONS: We conclude that (1) Mexican American women with PCOS are more insulin resistant than white women, (2) the incidence of insulin resistance is higher in Mexican American women with PCOS than in white women, (3) a single "screening" value for PCOS-related insulin resistance screening cannot be applied to both white and Mexican American women, and (4) normative values for insulin resistance screening in the PCOS population should be individualized for different racial or ethnic populations.

Adult↗

PubMed2002

Leptin and exercise.

Short-term exercise (<60 min) studies suggest that leptin concentrations are not acutely affected in healthy males and females. Most reports of reductions in serum leptin may be attributed to circadian rhythms or hemoconcentration. For long-term (> or =60 min) exercise, a reduction in leptin concentrations reported from 1 to 3 hr of running or cycling has been attributed to diurnal reduction in circulating leptin, independent of exercise. Exercise that produces a sufficient energy imbalance (kilocalorie intake versus kilocalorie expenditure) suppresses 24-hr mean and amplitude of the diurnal rhythm of leptin in women. Suppression of leptin concentrations may be counterbalanced by feeding and may explain consistent reports of reductions in leptin concentrations following extreme bouts of exercise such as marathons or ultramarathons. In addition, leptin concentrations are reduced 48 hr after long-term aerobic exercise and long-term resistance exercise is associated with delayed leptin reduction 9 hr postexercise. Training studies have documented that short-term exercise training (< or =12 weeks) does not affect leptin levels, with the exception of patients with type 2 diabetes. Exercise training protocols that result in reduced fat mass will lower leptin concentrations, thus, most investigators have reported leptin concentrations after accounting for fat loss. There are disparate findings concerning long-term (>12 weeks) training studies, with a number of studies finding no effect of training on leptin concentrations other than effects induced by fat loss, and other studies finding reductions in leptin concentrations after accounting for fat loss. Exercise training-induced reductions in leptin levels have been attributed to alterations in energy balance, improvements in insulin sensitivity, alterations in lipid metabolism, and unknown factors. Hormone replacement does not seem to affect leptin adaptations to training. Patients with type 2 diabetes show delayed effects of short-term resistance exercise on leptin concentrations, reduced leptin levels with long-term training, and appear to be more sensitive to training-induced leptin adaptations than other populations.

Energy Metabolism↗