Effects of neonatal castration and androgenization on sexual dimorphism in bone, leptin and corticosterone secretion

Mello, Wagner Garcez de; Morais, Sofia; Dornelles, Rita Cássia Menegati; Elias, Lucila Leico Kagohara; Castro, João César Bedran de

doi:10.1016/j.bone.2011.12.009

Cited by 12 publications

(5 citation statements)

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“…Clearly more reliable measurements of mineralizing and cellular activity will be achieved once a stable equilibrium of bone turnover has been reached by 3–4 months of age. Similar results of male versus female bone formation and turnover can be amply found in the literature [25–30] although a change during ageing and sexual maturation has not been specifically studied.…”

Section: Discussionsupporting

confidence: 74%

Computer-Automated Static, Dynamic and Cellular Bone Histomorphometry

et al. 2014

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Dynamic and cellular histomorphometry of trabeculae is the most biologically relevant way of assessing steady state bone health. Traditional measurement involves manual visual feature identification by a trained and qualified professional. Inherent with this methodology is the time and cost expenditure, as well as the subjectivity that naturally arises under human visual inspection. In this work, we propose a rapidly deployable, automated, and objective method for dynamic histomorphometry. We demonstrate that our method is highly effective in assessing cellular activities in distal femur and vertebra of mice which are injected with calcein and alizarin complexone 7 and 2 days prior to sacrifice. The mineralized bone tissues of mice are cryosectioned using a tape transfer protocol. A sequential workflow is implemented in which endogenous fluorescent signals (bone mineral, green and red mineralization lines), tartrate resistant acid phosphatase identified by ELF-97 and alkaline phosphatase identified by Fast Red are captured as individual tiled images of the section for each fluorescent color. All the images are then submitted to an image analysis pipeline that automates identification of the mineralized regions of bone and selection of a region of interest. The TRAP and AP stained images are aligned to the mineralized image using strategically placed fluorescent registration beads. Fluorescent signals are identified and are related to the trabecular surface within the ROI. Subsequently, the pipelined method computes static measurements, dynamic measurements, and cellular activities of osteoclast and osteoblast related to the trabecular surface. Our method has been applied to the distal femurs and vertebrae of 8 and 16 week old male and female C57Bl/6J mice. The histomorphometric results reveal a significantly greater bone turnover rate in female in contrast to male irrespective of age, validating similar outcomes reported by other studies.

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Section: Discussionsupporting

confidence: 74%

Computer-Automated Static, Dynamic and Cellular Bone Histomorphometry

et al. 2014

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“…Endocrine hormones regulate a diverse set of physiological responses, some of which include sexual dimorphism, reproductive capacity, glucose metabolism, and blood pressure (Cooper and Kavlock 1997; de Mello et al 2011; Dupont et al 2000; Lodish et al 2009; Ng et al 2001). The many types of responses regulated by hormones makes them of particular concern for disruption by xenobiotics (Ankley and Giesy 1998; Colborn and Clement 1992; Soto and Sonnenschein 2010; Tilghman et al 2010).…”

mentioning

confidence: 99%

Usingin VitroHigh Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals

Rotroff

Dix²,

Houck³

et al. 2013

Environ Health Perspect

143

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Background: Over the past 20 years, an increased focus on detecting environmental chemicals that pose a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP; thus, processing these chemicals using current test batteries could require millions of dollars and decades. A need for increased throughput and efficiency motivated the development of methods using in vitro high throughput screening (HTS) assays to prioritize chemicals for EDSP Tier 1 screening (T1S).Objective: In this study we used U.S. EPA ToxCast HTS assays for estrogen, androgen, steroidogenic, and thyroid-disrupting mechanisms to classify compounds and compare ToxCast results to in vitro and in vivo data from EDSP T1S assays.Method: We implemented an iterative model that optimized the ability of endocrine-related HTS assays to predict components of EDSP T1S and related results. Balanced accuracy was used as a measure of model performance.Results: ToxCast estrogen receptor and androgen receptor assays predicted the results of relevant EDSP T1S assays with balanced accuracies of 0.91 (p < 0.001) and 0.92 (p < 0.001), respectively. Uterotrophic and Hershberger assay results were predicted with balanced accuracies of 0.89 (p < 0.001) and 1 (p < 0.001), respectively. Models for steroidogenic and thyroid-related effects could not be developed with the currently published ToxCast data.Conclusions: Overall, results suggest that current ToxCast assays can accurately identify chemicals with potential to interact with the estrogenic and androgenic pathways, and could help prioritize chemicals for EDSP T1S assays.

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“…Testosterone treatment in infancy has emerged as a popular off-label treatment for boys with XXY, with observational reports of benefits in neurodevelopmental features [18, 19]. Animal models and limited clinical research have found that postnatal activation of the hypothalamic-pituitary-gonadal axis (known as the mini-puberty period of infancy) is a critical window of testosterone exposure during male development necessary for sexual differentiation of multiple tissues systemically [9, 11, 28]. The full implications of the mini-puberty period are still being studied, and rigorous research methods are desperately needed to guide standards of clinical care in XXY, as well as other populations that have impaired gonadal function in infancy [29].…”

Section: Discussionmentioning

confidence: 99%

Testosterone Treatment in Infants With 47,XXY: Effects on Body Composition

Davis

Reynolds

Dabelea

et al. 2019

Journal of the Endocrine Society

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ContextBoys with XXY have greater adiposity and a higher risk of cardiovascular disease. Infants with XXY have lower testosterone concentrations than typical boys, but no studies have evaluated adiposity in infants with XXY or the physiologic effects of giving testosterone replacement.ObjectiveTo determine the effect of testosterone on body composition in infants with XXY.DesignProspective, randomized trial.SettingTertiary care pediatric referral center.Participants20 infants 6 to 15 weeks of age with 47,XXY.InterventionTestosterone cypionate 25 mg intramuscularly monthly for three doses vs no treatment.Main Outcome MeasuresDifference in change in adiposity (percent fat mass z scores); other body composition measures, penile length, and safety outcomes between treated and untreated infants; and comparison with typical infants.ResultsThe increase in percent fat mass (%FM) z scores was greater in the untreated group than in the treated group (+0.92 ± 0.62 vs −0.12 ± 0.65, P = 0.004). Increases in secondary outcomes were greater in the testosterone-treated group for total mass, fat-free mass, length z score, stretched penile length, and growth velocity (P < 0.002 for all). At 5 months of age, adiposity in untreated infants with XXY was 26.7% compared with 23.2% in healthy male infants of the same age (P = 0.0037); there was no difference in %FM between the treated XXY boys and controls. Reported side effects were minimal and self-limited; no serious adverse events occurred.ConclusionsAdiposity of untreated infants was 15% greater than that of male controls by 5 months of age. Testosterone treatment for infants with XXY resulted in positive changes in body composition.

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Effects of neonatal castration and androgenization on sexual dimorphism in bone, leptin and corticosterone secretion

Cited by 12 publications

References 53 publications

Computer-Automated Static, Dynamic and Cellular Bone Histomorphometry

Computer-Automated Static, Dynamic and Cellular Bone Histomorphometry

Usingin VitroHigh Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals

Testosterone Treatment in Infants With 47,XXY: Effects on Body Composition

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