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Prolactin serum levels correlate with inflammatory status in drug-naive first-episode schizophrenia

Tue, 09/16/2014 - 2:17pm

Objectives. The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naive, first-episode schizophrenia patients with normal weight.

Methods. Patients with normal weight, drug-naive, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA).

Results. Sixty patients with normal weight, drug-naive, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1beta, IL-6 and TNF-alpha compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1beta, IL-6 and TNF-alpha within the schizophrenia group. Within the schizophrenia group, TNF-alpha was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration.

Conclusions. Patients with normal weight, drug-naive, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population.

Differential impact of anxiety symptoms and anxiety disorders on treatment outcome for psychotic depression in the STOP-PD study

Tue, 09/16/2014 - 2:17pm

BACKGROUND: There are conflicting results on the impact of anxiety on depression outcomes. The impact of anxiety has not been studied in major depression with psychotic features ("psychotic depression").

AIMS: We assessed the impact of specific anxiety symptoms and disorders on the outcomes of psychotic depression.

METHODS: We analyzed data from the Study of Pharmacotherapy for Psychotic Depression that randomized 259 younger and older participants to either olanzapine plus placebo or olanzapine plus sertraline. We assessed the impact of specific anxiety symptoms from the Brief Psychiatric Rating Scale ("tension", "anxiety" and "somatic concerns" and a composite anxiety score) and diagnoses (panic disorder and GAD) on psychotic depression outcomes using linear or logistic regression. Age, gender, education and benzodiazepine use (at baseline and end) were included as covariates.

RESULTS: Anxiety symptoms at baseline and anxiety disorder diagnoses differentially impacted outcomes. On adjusted linear regression there was an association between improvement in depressive symptoms and both baseline "tension" (coefficient=0.784; 95% CI: 0.169-1.400; p=0.013) and the composite anxiety score (regression coefficient = 0.348; 95% CI: 0.064-0.632; p=0.017). There was an interaction between "tension" and treatment group, with better responses in those randomized to combination treatment if they had high baseline anxiety scores (coefficient=1.309; 95% CI: 0.105-2.514; p=0.033). In contrast, panic disorder was associated with worse clinical outcomes (coefficient=-3.858; 95% CI: -7.281 to -0.434; p=0.027) regardless of treatment.

CONCLUSIONS: Our results suggest that analysis of the impact of anxiety on depression outcome needs to differentiate psychic and somatic symptoms.

Reducing Recidivism and Symptoms in Emerging Adults with Serious Mental Health Conditions and Justice System Involvement

Tue, 09/16/2014 - 2:17pm

The peak years of offending in the general population and among those with serious mental health conditions (SMHC) are during emerging adulthood. There currently are no evidence-based interventions for reducing offending behavior among 18-21 year olds, with or without SMHC. This open trial examined outcomes from an adaptation of Multisystemic Therapy (MST), an effective juvenile recidivism reduction intervention, modified for use with emerging adults with SMHC and recent justice system involvement. MST for emerging adults (MST-EA) targets MH symptoms, recidivism, problem substance use, and young adult functional capacities. All study participants (n = 41) were aged 17-20 and had a MH diagnosis and recent arrest or incarceration. Implementation outcomes indicated that MST-EA was delivered with strong fidelity, client satisfaction was high, and the majority of participants successfully completed the intervention. Research retention rates also were high. Pre-post-analyses revealed significant reductions in participants' MH symptoms, justice system involvement, and associations with antisocial peers.

Effect of diet on brain metabolites and behavior in spontaneously hypertensive rats

Tue, 09/16/2014 - 2:17pm

Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous psychiatric disorder affecting 5-10% of children. One of the suggested mechanisms underlying the pathophysiology of ADHD is insufficient energy supply to neurons. Here, we investigated the role of omega 3 fatty acids in altering neural energy metabolism and behavior of spontaneously hypertensive rats (SHR), which is an animal model of ADHD. To this end, we employed Proton Magnetic Resonance Spectroscopy ((1)H MRS) to evaluate changes in brain neurochemistry in the SHR following consumption of one of three experimental diets (starting PND 21): fish oil enriched (FOE), regular (RD) and animal fat enriched (AFE) diet. Behavioral tests were performed to evaluate differences in locomotor activity and risk-taking behavior (starting PND 44). Comparison of frontal lobe metabolites showed that increased amounts of omega 3 fatty acids decreased total Creatine levels (tCr), but did not change Glutamate (Glu), total N-Acetylaspartate (tNAA), Lactate (Lac), Choline (Cho) or Inositol (Ino) levels. Although behavior was not significantly affected by different diets, significant correlations were observed between brain metabolites and behavior in the open field and elevated plus maze. SHR with higher levels of brain tCr and Glu exhibited greater hyperactivity in a familiar environment. On the other hand, risk-taking exploration of the elevated plus maze's open arms correlated negatively with forebrain tNAA and Lac levels. These findings support the possible alteration in energy metabolites in ADHD, correlating with hyperactivity in the animal model. The data also suggest that omega 3 fatty acids alter brain energy and phospholipid metabolism.

Planning Data Management Education Initiatives: Process, Feedback, and Future Directions

Mon, 09/15/2014 - 11:16am

Educating researchers in sound data management skills is a hot topic in today’s data intensive research world. Librarians across the country and the world are taking the lead in offering this training to their campus research communities. In Fall, 2013, the Data Curation Librarian at the University of Tennessee, Knoxville, held a one-day “Data Management Basics” Workshop geared towards graduate students in engineering and science disciplines based on the New England Collaborative Data Management Curriculum. Students were asked to complete a pre-workshop survey and a series of seven post-module surveys throughout the day. This article discusses the results of the survey feedback, the planning process, and elaborates on important variables in planning data management training initiatives, such as disciplinary adjustments and time constraints. The article concludes with a discussion of the author’s future plans for providing training initiatives based on the feedback he received.

Guidelines for the use of growth hormone in children with short stature.

Wed, 09/10/2014 - 2:51pm

On the basis of the information currently available, the only conditions in which GH therapy appears to be safe and effective in increasing adult height are GH deficiency and, likely, Turner syndrome. Therapy with GH also increases the growth velocity of children with CRI and may increase adult height, but no long-term data are available. Encouraging short-term results have been reported in patients with a few other conditions, such as patients with glucocorticoid-induced growth failure, renal transplantation, and Prader-Willi syndrome, but the data are limited and no long-term studies have been reported; in many other conditions the data are either inconclusive or discouraging. For children in these latter groups, GH therapy should be considered investigational and undertaken only as part of ethically sound, controlled clinical trials. Knowledge concerning the conditions in which GH is safe and effective is a prerequisite to making rational decisions concerning its use. However, in deciding whether therapy is warranted in an individual child, one must consider other important factors. The age and emotional maturity of the child, the family structure and dynamics, and even financial considerations may, in some cases, outweigh the presence of a GH-responsive condition. Likewise, the child's and the family's views about "short" stature and the likely benefits of therapy must be considered. Ultimately, a decision concerning the appropriateness of GH therapy must be individualized and based on a realistic assessment of its impact on the quality of life of the child and future adult.

Male pubertal development: are endocrine-disrupting compounds shifting the norms

Wed, 09/10/2014 - 2:51pm

Endocrine-disrupting compounds (EDCs) are synthetic or natural compounds that interfere with endogenous endocrine action. The frequent use of chemicals with endocrine active properties in household products and contamination of soil, water, and food sources by persistent chemical pollutants result in ubiquitous exposures. Wildlife observations and animal toxicological studies reveal adverse effects of EDCs on reproductive health. In humans, a growing number of epidemiological studies report an association with altered pubertal timing and progression. While these data are primarily reported in females, this review will focus on the small number of studies performed in males that report an association of polychlorinated biphenyls with earlier sexual maturity rating and confirm subtle effects of lead, dioxins, and endosulfan on delaying pubertal onset and progression in boys. Recent studies have also demonstrated that EDC exposure may affect pubertal testosterone production without having a noticeable effect on sexual maturity rating. A limitation to understand the effects of EDCs in humans is the potential for confounding due to the long temporal lag from early-life exposures to adult outcomes. The complex interplay of multiple environmental exposures over time also complicates the interpretation of human studies. These studies have identified critical windows of vulnerability during development when exposures to EDCs alter critical pathways and affect postnatal reproductive health. Contemporaneous exposures can also disrupt the hypothalamic-pituitary-gonadal axis. This paper will review the normal process of puberty in males and summarize human data that suggest potential perturbations in pubertal onset and tempo with early-life exposures to EDCs.

Mullerian inhibiting substance: a gonadal hormone with multiple functions

Wed, 09/10/2014 - 2:51pm

Mullerian inhibiting substance (MIS) is the gonadal hormone that causes regression of the Mullerian ducts, the anlagen of the female internal reproductive structures, during male embryogenesis. MIS is a member of the large transforming growth factor-beta (TGF beta) multigene family of glycoproteins that are involved in the regulation of growth and differentiation. The proteins in this gene family are all produced as dimeric precursors and undergo posttranslational processing for activation, requiring cleavage and dissociation to release bioactive C-terminal fragments. Similarly, the 140 kilodalton (kDa) disulfide-linked homodimer of MIS is proteolytically cleaved to generate its active C-terminal fragments. The sexually dimorphic expression of MIS in Sertoli cells of the testis and granulosa cells of the ovary is critical for normal differentiation of the internal reproductive tract structures. A number of extra-Mullerian functions such as control of germ cell maturation and gonadal morphogenesis, induction of the abdominal phase of testicular descent, suppression of lung maturation, and growth inhibition of transformed cells have also been proposed for this growth-inhibitory hormone and will be discussed. This article will summarize the current understanding of the biology and multiple functions of MIS including its activation, regulation, and mechanism of action and discuss areas of interest in ongoing research.

Predictors of serum chlorinated pesticide concentrations among prepubertal Russian boys

Wed, 09/10/2014 - 2:51pm

BACKGROUND: Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals.

OBJECTIVES: Our goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p -DDE)-among boys in Chapaevsk, Russia.

METHODS: Between 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and beta-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys' serum HCB, beta-HCH, and p,p -DDE concentrations.

RESULTS: Among 355 boys with OCP measurements, median serum HCB, beta-HCH, and p,p -DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and beta-HCH concentrations, respectively, than boys who lived >/= 5 km away. Living > 3 years in Chapaevsk predicted higher beta-HCH concentrations, and having parents who lacked a high school education predicted higher p,p -DDE concentrations.

CONCLUSIONS: Among this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex.

Parental mastery of continuous subcutaneous insulin infusion skills and glycemic control in youth with type 1 diabetes

Wed, 09/10/2014 - 2:51pm

OBJECTIVE: The purpose of this study is to determine whether parental knowledge of the continuous subcutaneous insulin infusion (CSII) device affects glycemic control as measured by hemoglobin A1c (A1C) level.

SUBJECTS AND METHODS: Parents of children with type 1 diabetes mellitus (T1DM) using CSII completed a 14-item questionnaire. Questions 1-10 were knowledge-based questions that required the parent to extract specific information from their child's CSII device. Questions 11-14 asked parents to provide a self-assessment of their CSII knowledge.

RESULTS: Twenty-two parents of youth with T1DM participated in the study. Ten of the youth were in the Low-A1C group (A1C/=8%). Parents of youth in the Low-A1C group scored statistically better on the 10-item performance survey than parents of youth in the High-A1C group. Most of the parents of children in the Low-A1C group responded that they knew their child's insulin pump "very well" and that their pump knowledge had "increased" since their child started on the insulin pump.

CONCLUSIONS: Our findings reveal that youth with T1DM whose parents are more knowledgeable about pump functions have optimal glycemic control as evidenced by A1C. These findings underscore the importance of ongoing pump training for both pediatric patients and their parents.

Blood lead levels and serum insulin-like growth factor 1 concentrations in peripubertal boys

Wed, 09/10/2014 - 2:51pm

BACKGROUND: Childhood lead exposure has been associated with growth delay. However, the association between blood lead levels (BLLs) and insulin-like growth factor 1 (IGF-1) has not been characterized in a large cohort with low-level lead exposure.

METHODS: We recruited 394 boys 8-9 years of age from an industrial Russian town in 2003-2005 and followed them annually thereafter. We used linear regression models to estimate the association of baseline BLLs with serum IGF-1 concentration at two follow-up visits (ages 10-11 and 12-13 years), adjusting for demographic and socioeconomic covariates.

RESULTS: At study entry, median BLL was 3 mug/dL (range, < 0.5-31 mug/dL), most boys (86%) were prepubertal, and mean +/- SD height and BMI z-scores were 0.14 +/- 1.0 and -0.2 +/- 1.3, respectively. After adjustment for covariates, the mean follow-up IGF-1 concentration was 29.2 ng/mL lower (95% CI: -43.8, -14.5) for boys with high versus low BLL (>/= 5 mug/dL or < 5 mug/dL); this difference persisted after further adjustment for pubertal status. The association of BLL with IGF-1 was stronger for mid-pubertal than prepubertal boys (p = 0.04). Relative to boys with BLLs < 2 mug/dL, adjusted mean IGF-1 concentrations decreased by 12.8 ng/mL (95% CI: -29.9, 4.4) for boys with BLLs of 3-4 mug/dL; 34.5 ng/mL (95% CI: -53.1, -16.0) for BLLs 5-9 mug/dL; and 60.4 ng/mL (95% CI: -90.9, -29.9) for BLLs >/= 10 mug/dL.

CONCLUSIONS: In peripubertal boys with low-level lead exposure, higher BLLs were associated with lower serum IGF-1. Inhibition of the hypothalamic-pituitary-growth axis may be one possible pathway by which lead exposure leads to growth delay.

Development and pilot testing of a parent education intervention for type 1 diabetes: parent education through simulation-diabetes

Wed, 09/10/2014 - 2:51pm

PURPOSE: To purpose of the pilot study was to evaluate the use of a pediatric human patient simulator (HPS) to teach parents diabetes management for their children newly diagnosed with type 1 diabetes, referred to as Parent Education Through Simulation-Diabetes.

METHODS: A focus group study and 2 pilot studies (1-group study and a randomized 2-group study) were used to develop and test a teaching intervention. Parents were recruited from the Pediatric Diabetes Clinic at UMass Memorial Medical Center. A brainstorming group (n = 6) discussed the simulator concept and what modifications would be necessary to enhance parent teaching; the authors also developed the initial hypoglycemia and hyperglycemia teaching vignettes. Two focus groups (n = 13) discussed the acceptance of using a simulator and the timing and content of the teaching sessions. Based on their recommendations, a 1-group pretest-posttest pilot was conducted with parents (n = 10) receiving hypoglycemia education enhanced with the HPS, followed by a randomized 2-group pilot study (n = 16).

FINDINGS: The focus group participants enthusiastically supported the use of the pediatric HPS after diagnosis and made recommendations for the timing and content of the teaching sessions. Major findings from the pilot work included (1) successful recruitment of 16 participants from only 1 site within 6 weeks, (2) instrument reliability demonstrated for all scales, and (3) mean change from baseline in the predicted direction for all measures.

CONCLUSIONS: The HPS has the potential of providing parents an innovative means of learning diabetes management through visualization during the early months after diagnosis and so warrants a powered study to determine its efficacy.

The increased incidence of congenital hypothyroidism: fact or fancy

Wed, 09/10/2014 - 2:51pm

OBJECTIVE: The incidence of congenital hypothyroidism (CH) detected by newborn screening in the US has increased significantly since the early 1990s. We defined the characteristics associated with the increased incidence.

PATIENTS: A cohort of children with CH born during an earlier period of low incidence (1991-94) was compared with a cohort born during a later period when the incidence of CH had doubled (2001-04).

MEASUREMENTS: Screening was performed with T4 as the primary marker and thyroid stimulating hormone (TSH) on selected specimens. Follow-up on hypothyroid children determined whether they had permanent or transient hypothyroidism. Cases were classified based on laboratory results: initial TSH >/=100 mU/l was 'severe,' initial TSH /l but >/=20 mU/l was 'mild' and initial TSH /l with subsequent abnormal TSH was 'delayed'.

RESULTS: The overall incidence of CH almost doubled between the two time periods, from 1:3010 to 1:1660. Excess cases were found in the mild and delayed categories, with no increase in severe cases. The proportion of transient cases was <5% in severe cases, 40% in mild cases and 70% among delayed cases. There was no difference in the proportion of transient case between the two time periods. Modifications to the T4/TSH testing protocol between the two time periods resulted in substantially increased numbers of specimens in the younger cohort being selected for TSH testing in both initial and repeat specimens.

CONCLUSION: The rising incidence of CH in Massachusetts is confined to mild and delayed cases. Our findings suggest that this rise is attributable to enhanced detection rather than an absolute increase in numbers.

Mentoring fathers of children newly diagnosed with T1DM

Wed, 09/10/2014 - 2:51pm

PURPOSE: To pilot test a social support intervention for fathers of children (T1DM).

DESIGN AND METHODS: The pilot study was part of a larger randomized, controlled clinical trial. Father participants (28 fathers of children newly diagnosed) were recruited from two pediatric diabetes centers. For 12 months fathers (n = 19) and their spouses in the experimental arm received social support (home visits and phone calls). Control group fathers (n = 9) and their spouses received the phone number of an experienced parent (but not formally educated to provide social support) to call as needed.

RESULTS: Fathers in the intervention group had significantly greater confidence but scored higher on worry at 12 months than control group fathers. Fathers in the two groups did not differ significantly in disease-related concerns or perceived disease impact on the family, nor did they differ significantly in perceived amount and helpfulness of their daily management. However, mothers overall perceived fathers as contributing more care and help than fathers perceived themselves (p > .10). Fathers in the experimental arm identified parent mentors as individuals they would seek advice regarding day-to-day management and community agencies. Over this 4.5 year study, 6 of 28 father participants and two of the three father mentors dropped out.

CLINICAL IMPLICATIONS: Nurses caring for families with young children newly diagnosed with T1DM should consider fathers social support needs and encourage their participation in day-to-day management.

Serum concentrations of organochlorine pesticides and growth among Russian boys

Wed, 09/10/2014 - 2:51pm

BACKGROUND: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth.

OBJECTIVE: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels.

METHODS: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders.

RESULTS: Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), beta-hexachlorocyclohexane (betaHCH), and p,p -dichlorodiphenyldichloroethylene (p,p -DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, betaHCH, and p,p -DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p -DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile.

CONCLUSIONS: Serum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.

Predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia: a cross-sectional pilot study

Wed, 09/10/2014 - 2:51pm

BACKGROUND: Toxicological studies and limited human studies have demonstrated associations between exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) and adverse developmental and reproductive health effects. Given that children may be particularly susceptible to reproductive and developmental effects of organochlorines, and the paucity of information available regarding childhood exposures to dioxins in particular, we undertook a pilot study to describe the distribution of, and identify potential predictors of exposure to, dioxin-like compounds and dioxins among adolescent boys in Chapaevsk, Russia. The pilot study was also designed to guide the development of a large prospective cohort study on the relationship of exposure to PCDDs, PCDFs, and PCBs with growth and pubertal development in peri-pubertal Chapaevsk boys.

METHODS: 221 boys age 14 to 17 participated in the pilot study. Each of the boys, with his mother, was asked to complete a nurse-administered detailed questionnaire on medical history, diet, and lifestyle. The diet questions were used to measure the current and lifetime consumption of locally grown or raised foods. Blood samples from 30 of these boys were sent to the Centers for Disease Control and Prevention (CDC) for analysis of dioxins, furans and PCBs.

RESULTS: The median (25th, 75th percentile) concentrations for total PCDDs, PCDFs and coplanar PCBs were 95.8 pg/g lipids (40.9, 144), 33.9 pg/g lipids (20.4, 61.8), and 120 pg/g lipids (77.6, 157), respectively. For WHO-TEQs, the median (25th, 75th percentile) for total PCDDs, PCDFs, and coplanar PCBs were 0.29 (0.1, 9.14), 7.98 (5.27, 12.3), and 7.39 (4.51, 11.9), respectively. Although TCDD was largely non-detectable, two boys had high TCDD levels (17.9 and 21.7 pg/g lipid). Higher serum levels of sum of dioxin-like compounds and sum of dioxin TEQs were positively associated with increased age, consumption of fish, local meats other than chicken, PCB 118, and inversely with weeks of gestation.

CONCLUSION: The total TEQs among Chapaevsk adolescents were higher than most values previously reported in non-occupationally exposed populations of comparable or even older ages. Dietary consumption of local foods, as well as age and weeks of gestation, predicted dioxin exposure in this population.

Mullerian-inhibiting substance inhibits rat Leydig cell regeneration after ethylene dimethanesulphonate ablation

Wed, 09/10/2014 - 2:51pm

The postnatal development of Leydig cell precursors is postulated to be controlled by Sertoli cell secreted factors, which may have a determinative influence on Leydig cell number and function in sexually mature animals. One such hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor lines. To further delineate the effects of MIS on Leydig cell proliferation and steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS) model of Leydig cell regeneration. Following EDS ablation of differentiated Leydig cells in young adult rats, recombinant MIS or vehicle was delivered by intratesticular injection for 4 days (Days 11-14 after EDS). On Days 15 and 35 after EDS (1 and 21 days post-MIS injections), endocrine function was assessed and testes were collected for stereology, immunohistochemistry, and assessment of proliferation and steroidogenesis. Although serum testosterone and luteinizing hormone (LH) were no different, intratesticular testosterone was higher on Day 35 in MIS-treated animals. At both time points, intratesticular 5alpha-androstan-3alpha,17beta-diol concentrations were much higher than that of testosterone. MIS-treated animals had fewer mesenchymal precursors on Day 15 and fewer differentiated Leydig cells on Day 35 with decreased numbers of BrdU+ nuclei. Apoptotic interstitial cells were observed only in the MIS-treated testes, not in the vehicle-treated group on Day 15. These data suggest that MIS inhibits regeneration of Leydig cells in EDS-treated rats by enhancing apoptotic cell death as well as by decreasing proliferative capacity.