Breast Development (breast + development)

Distribution by Scientific Domains

Selected Abstracts

Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty

A. Mouritsen
Summary A recent decline in onset of puberty , especially among girls , has been observed, first in the US in the mid-1990s and now also in Europe. The development of breast tissue in girls occurs at a much younger age and the incidence of precocious puberty (PP) is increasing. Genetic factors and increasing prevalence of adiposity may contribute, but environmental factors are also likely to be involved. In particular, the widespread presence of endocrine-disrupting chemicals (EDCs) is suspected to contribute to the trend of earlier pubertal onset. The factors regulating the physiological onset of normal puberty are poorly understood. This hampers investigation of the possible role of environmental influences. There are many types of EDCs. One chemical may have more than one mode of action and the effects may depend on dose and duration of the exposure, as well as the developmental stage of the exposed individual. There may also be a wide range of genetic susceptibility to EDCs. Human exposure scenarios are complex and our knowledge about effects of mixtures of EDCs is limited. Importantly, the consequences of an exposure may not be apparent at the actual time of exposure, but may manifest later in life. Most known EDCs have oestrogenic and/or anti-androgenic actions and only few have androgenic or anti-oestrogenic effects. Thus, it appears plausible that they interfere with normal onset of puberty. The age at menarche has only declined by a few months whereas the age at breast development has declined by 1 year; thus, the time span from initiation of breast development to menarche has increased. This may indicate an oestrogen-like effect without concomitant central activation of the hypothalamic,pituitary axis. The effects may differ between boys and girls, as there are sex differences in age at onset of puberty, hormonal profiles and prevalence of precocius puberty. [source]

Endocrine disrupters and human puberty

Summary In this overview of the literature, epidemiological research studying the effect of endocrine disrupters on the onset of puberty is summarized. In girls, earlier age at menarche was reported after exposure to polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), persistent pesticides [dichlorodiphenyltrichloroethane (DDT)] and phthalate esters. However, several other studies found no effect of these compounds on age at menarche or pubertal Tanner stages. One study reported a delaying effect of dioxin-like compounds on breast development. In boys, exposure to PCBs, PCDFs or the pesticide endosulfan was associated with delayed puberty or decreased penile length. Much of the results found in population studies are in accordance with experimental studies in animals. However, the mixture of different components with antagonistic effects (oestrogenic, anti-oestrogenic, anti-androgenic) and the limited knowledge about the most critical window for exposure (prenatal, peri-natal and pubertal) may hamper the interpretation of results. [source]

Predictive factors for organic central precocious puberty and utility of simplified gonadotropin-releasing hormone tests

Abstract Background: The aim of the present study was to determine whether the clinical presentation of patients with central precocious puberty (CPP) permits differentiation between idiopathic and organic forms, and to examine whether luteinizing hormone (LH) determination in single blood sample after gonadotropin-releasing hormone (GnRH) administration is sufficient to diagnose CPP. Methods: Potential clinical and laboratory predictors for the presence of central nervous system (CNS) abnormalities were assessed. Sensitivities and specificities of LH and follicle-stimulating hormone (FSH) levels at 0, 15, 30, 60, 90 and 120 min were compared after GnRH stimulation. Results: In 45 girls with signs of breast development, 26 were diagnosed as having CPP. The age of onset in patients with organic CPP was 4.75 2.01 years (range 1.2,7.1 years, median 5.0 years), whereas the age in patients with idiopathic CPP was 7.09 0.87 years (range 5.0,7.9 years, median 7.0 years). This parameter is the only one showing statistical significance. In addition, the specimen at 30 min after GnRH stimulation yielded highest sensitivity for the diagnosis of CPP. Conclusions: The earlier the onset of disease, the higher the possibility of presence of CNS lesion. According to the mean GnRH-stimulated LH levels and sensitivity at each time, a single blood sample obtained for LH determined after GnRH administration at 30 min can be used to diagnose CPP. [source]

A Giant Juvenile Fibroadenoma in a 12-Year-Old Girl: A Case for Breast Conservation

Rache M. Simmons MD
Abstract: A 12-year-old girl presented to our service for evaluation of a rapidly enlarging 16 cm breast mass. The mass was removed by local excision and diagnosed to be a giant juvenile fibroadenoma. She had normal breast development over a 1-year postoperative follow-up period. We present this case to illustrate the diagnosis and management of large breast tumors in the adolescent age group, and to emphasize that these tumors are almost always benign and should be treated with breast-conserving surgery. [source]

Estrogen/isoflavone interactions in cynomolgus macaques (Macaca fascicularis)

J. Mark Cline
Abstract Soy isoflavones are phytoestrogenic components of dietary soy, which are widely consumed for their potential health benefits. Soy isoflavones appear to decrease breast and endometrial cancer risk in human observational studies, but paradoxically stimulate growth of breast cancer cells in culture and uterine enlargement in rodents. We have shown that these compounds are not estrogenic in cynomolgus monkeys even at relatively high doses, but that they reduce estrogen-induced proliferative responses of the breast and endometrium. This effect may be mediated through estrogen receptor interactions and/or modulation of endogenous estrogen metabolism. Interindividual variation in isoflavone absorption and metabolism contributes to the degree of estrogen antagonistic effect. Our recent studies have also shown that individual isoflavone metabolites such as glyceollins may have unique selective estrogen receptor modulator-like activity, acting as tissue-specific antagonists without agonist activity. Rodent studies and human epidemiologic data suggest that timing of exposure and dose relative to endogenous estrogen concentrations are important determinants of effect, and studies of dietary soy on breast development and pubertal maturation are under way. Because soy isoflavones are both abundant in standard monkey chow diets and widely available as dietary supplements for human beings, these findings have broad relevance to the health of human and nonhuman primates. Am. J. Primatol. 71:722,731, 2009. 2009 Wiley-Liss, Inc. [source]

The role of the RNA-binding protein Sam68 in mammary tumourigenesis,

David J Elliott
Abstract The RNA binding protein Sam68 (Src- associated in mitosis 68 kD) is implicated in cell signalling, transcriptional regulation, pre-mRNA splicing, and is overexpressed and/or hyperphosphorylated in breast, prostate, and renal cancers. Sam68 has roles in normal breast development; however, a study by Song et al published in this issue of The Journal of Pathology reports overexpression of nuclear and cytoplasmic Sam68 protein in a large cohort of clinical breast tumours, implicating Sam68 as a potential prognostic indicator and target for therapy. In breast cancer cells, nuclear Sam68 protein might affect the expression of cancer-relevant genes and/or modulate exon splicing patterns in a dose-dependent manner. Sam68-regulated expression of alternative transcripts may help drive mammary tumourigenesis. The high levels of cytoplasmic Sam68 protein observed in breast cancer cells could also impact on cellular signalling pathways important for mammary tumour cell biology. Copyright 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Invited Commentary for Song L et al. Sam68 up-regulation correlates with, and its down-regulation inhibits, proliferation and tumourigenicity of breast cancer cells. Journal of Pathology, [source]

Age of puberty: Data from the United States of America,

APMIS, Issue 2 2001
Review article
In an attempt to determine whether the secular trend toward an earlier onset of puberty has continued over recent decades in the United States of America, published reports concerning the age of attainment of pubertal events have been reviewed. Such reports are very limited and vary in both design and inclusive ages of study subjects. Among females, two recent large cross-sectional studies indicate that fifty percent of females in the United States attain Tanner breast stage 2 at 9.5 to 9.7 years of age. This is younger than previously thought, although adequate earlier studies of girls in the United States are not available for comparison. These two studies also indicate that about 14% of girls attain Tanner stage 2 while 8 years of age; one study extends earlier reporting that about 6% exhibit onset of breast development while 7 years of age. There is no evidence that the age of menarche or the attainment of adult (Tanner 5) breast development has decreased over the past 30 years. The data also suggest an earlier onset of Tanner stage 2 pubic hair but no change in attainment of stage 5. Among males, pubic hair may be appearing at younger ages, but data are inadequate or too inconsistent to allow firm interpretation. The lack of standardization of genital criteria of pubertal onset in the male makes any conclusions regarding secular trends impossible. In summary, earlier secular trends over recent decades related to better health, improved nutrition or socio-economic status, or any putative influence by endocrine disrupters cannot be verified. [source]

The cytochrome P450 aromatase lacking exon 5 is associated with a phenotype of nonclassic aromatase deficiency and is also present in normal human steroidogenic tissues

Carolina M. Pepe
Summary Objective, The previously described c655G>A mutation of the human cytochrome P450 aromatase gene (P450aro, CYP19) results in aberrant splicing due to disruption of a donor splice site. To explain the phenotype of partial aromatase deficiency observed in a female patient described with this mutation, molecular consequences of the c655G>A mutation were investigated. Design To investigate whether the c655G>A mutation causes an aberrant spliced mRNA lacking exon 5 (,Ex5), P450aro RNA was analysed from the patient's lymphocytes by reverse transcription polymerase chain reaction (RT-PCR) and by splicing assays performed in Y1 cells transfected with a P450aro ,Ex5 expression vector. Aromatase activity of the c655G>A mutant was predicted by three dimensional (3D) protein modelling studies and analysed in transiently transfected Y1 cells. Exon 5 might be predicted as a poorly defined exon suggesting a susceptibility to both splicing mutations and physiological alternative splicing events. Therefore, expression of the ,Ex5 mRNA was also assessed as a possibly naturally occurring alternative splicing transcript in normal human steroidogenic tissues. Patients An aromatase deficient girl was born with ambiguous genitalia. Elevated serum LH, FSH and androgens, as well as cystic ovaries, were found during prepuberty. At the age of 84 years, spontaneous breast development and a 1946 pmol/l serum oestradiol level was observed. Results The ,Ex5 mRNA was found in lymphocytes of the P450aro deficient girl and her father, who was a carrier of the mutation. Mutant minigene expression resulted in complete exon 5 skipping. As expected from 3D protein modelling, ,Ex5 cDNA expression in Y1 cells resulted in loss of P450aro activity. In addition, the ,Ex5 mRNA was present in placenta, prepubertal testis and adrenal tissues. Conclusions Alternative splicing of exon 5 of the CYP19 gene occurs in the wild type (WT) as well as in the c655G>A mutant. We speculate that for the WT it might function as a regulatory mechanism for aromatization, whereas for the mutant a relative prevalence of the shorter over the full-length protein might explain the phenotype of partial aromatase deficiency. [source]

Poor uterine development in Turner syndrome with oral oestrogen therapy

Wendy F. Paterson
Summary OBJECTIVE To evaluate uterine development in Turner syndrome (TS) patients in relation to treatment with oral ethinyl oestradiol (E2) for pubertal induction. DESIGN AND PATIENTS Pelvic ultrasound data for 96 TS patients scanned since 1989 were analysed. Patients were classified into three groups: (1) untreated (n = 48); (2) complete spontaneous puberty (n = 10); and (3) treated with ethinyl oestradiol (n = 38). Uterine development was described in the three groups and compared with the normal data. MEASUREMENTS Uterine length, fundal-cervical ratio (FCR) and shape were recorded, and presence or absence of ovaries noted. In the treated group, cross-sectional and longitudinal data were combined to compare uterine development with Tanner breast stage. RESULTS In untreated girls up to age 10 years there was a variable distribution of uterine length and FCR about the mean. Thereafter, the uterus failed to grow and mature normally. Girls with complete spontaneous puberty had morphologically normal ovaries and uteri, but of 7 girls who attained menarche, 3 subsequently developed secondary oligomenorrhoea or amenorrhoea. In the treated group, in general, breast development and uterine length progressed with increasing E2 dose. However, only 50% of girls with complete secondary sexual development had a mature heart-shaped uterine configuration. CONCLUSIONS Our current E2 treatment regimen for TS girls gives rise to satisfactory pubertal induction and maintenance, but failed to induce a fully mature uterus in half the cohort. In view of the high risk of miscarriage in TS in both spontaneous and assisted pregnancies, the effect of more physiological methods of E2 replacement on uterine development should be investigated. [source]

Mastitis in early infancy

T Stricker
Abstract Aim: To evaluate the clinical features and microbiological findings in young infants with mastitis. Methods: Retrospective review of medical records of 18 infants with breast inflammation during the first 3 mo of life seen in the paediatric emergency department between 1992 and 2002. Results: All were full-term infants with female,male ratio of 3.5,1. The age ranged from 12 to 45 d, with a peak in the 4th and 5th weeks of life. Only five patients had systemic manifestations, and five were pretreated with oral antibiotics (amoxicillin-clavulanic acid). The latter as well as seven additional cases required incision and drainage due to abscess formation. Bacterial cultures grew Staphylococcus aureus in 10 cases including all pretreated infants. In four of these cases, Gram stain showed the pathogen. After antimicrobial treatment, no recurrence was observed in any of the patients. Conclusions: These findings suggest that mastitis in early infancy should be treated with parenteral antibiotics guided by Gram stain when available and informative. Otherwise, ,-lactamase-resistant antibiotics are a reasonable empirical initial treatment pending culture results. Optimizing the management of infants with mastitis is important especially since abscess formation requiring incision may be detrimental for later breast development. [source]