Growth and Bone Mineral Density Changes in Ovariectomized Rats Treated with Estrogen Receptor Alpha or Beta Agonists

Background@#Estrogen controls the pubertal growth spurt, growth plate closure, and accretion of bone mineral density (BMD) of long bones after biding estrogen receptor (ER).There are two subtypes of ER, ERα and ERβ. If each ER subtype has different effects, we may control those actions by manipulating the estrogen binding intensity to each ER subtype and increase the final adult height without markedly reducing BMD or impairing reproductive functions. The purpose of our study was to compare these effects of ERα and ERβ on long bones in ovariectomized rats. @*Methods@#Thirty female rats were ovariectomized and randomly divided into 3 groups. The control, propylpyrazole triol (PPT), and 2,3-bis (4-hydroxyphenyl) propionitrile (DPN) groups were subcutaneously injected for 5 weeks with sesame oil, PPT as an ERα agonist, and DPN as an ERβ agonist, respectively. The crown-lump length and body weight were measured weekly.BMD, serum levels of growth hormone (GH) and estradiol were checked before and after 5 weeks of injections. Pituitary GH1 expression levels were determined with quantitative realtime polymerase chain reaction, the proximal tibias were dissected, decalcified and stained with hematoxylin-eosin, and the thicknesses of epiphyseal plates including proliferative and hypertrophic zones were measured in 20-evenly divided sites after 5 weeks of injections. Comparisons for auxological data, serum hormone and pituitary GH1 expression levels, BMD, and epiphyseal plate thicknesses among 3 groups before and after injections were conducted. @*Results@#There was no significant difference in body lengths among 3 groups. The body weights were significantly lower, but, serum GH, pituitary GH1 expression levels, and BMDs were higher in PPT group than the other 2 groups after 5 weeks of injections. There was no significant difference in the thicknesses of the total epiphyseal plate, proliferative, and hypertrophic zone among 3 groups. @*Conclusion@#ERα is more involved in pituitary GH secretion and bone mineral deposition than ERβ. Weight gain might be prevented with the ERα agonist.

Percentile Distributions of Birth Weight according to Gestational Ages in Korea (2010-2012)

The Pediatric Growth Chart (2007) is used as a standard reference to evaluate weight and height percentiles of Korean children and adolescents. Although several previous studies provided a useful reference range of newborn birth weight (BW) by gestational age (GA), the BW reference analyzed by sex and plurality is not currently available. Therefore, we aimed to establish a national reference range of neonatal BW percentiles considering GA, sex, and plurality of newborns in Korea. The raw data of all newborns (470,171 in 2010, 471,265 in 2011, and 484,550 in 2012) were analyzed. Using the Korean Statistical Information Service data (2010-2012), smoothed percentile curves (3rd-97th) by GA were created using the lambda-mu-sigma method after exclusion and the data were distinguished by all live births, singleton births, and multiple births. In the entire cohort, male newborns were heavier than female newborns and singletons were heavier than twins. As GA increased, the difference in BW between singleton and multiples increased. Compared to the previous data published 10 years ago in Korea, the BW of newborns 22-23 gestational weeks old was increased, whereas that of others was smaller. Other countries' data were also compared and showed differences in BW of both singleton and multiple newborns. We expect this updated data to be utilized as a reference to improve clinical assessments of newborn growth.

Comparison of growth and pubertal progression in wild type female rats with different bedding types

PURPOSE: Endocrine-disrupting chemicals interfere with the endocrine system and therefore affect growth and pubertal progression. The study aim was to compare the growth and pubertal progression in wild-type female rats with different bedding types. METHODS: Twenty 5-week-old female wild-type Sprague Dawley rats were randomly assigned to two groups with different bedding types: one group received wood shaving bedding, while a second group received corncob bedding. We determined crown-rump length and body weight as anthropometric measurements and assessed the serum growth hormone (GH) and estradiol levels. The gh1 mRNA expression levels were compared using quantitative real time transcription polymerase chain reaction. The estrous cycle was evaluated by vaginal smear. RESULTS: The anthropometric measurements were not significantly different between the two groups. The mean relative expression of the gh1 gene was lower in the corncob bedding group than that in the wood shaving group (P=0.768). Meanwhile serum GH and estradiol were increased in the wood shaving bedding group; however this difference was not statistically significant. The time to first estrus and the length of the estrous cycle were increased in the corncob bedding group; the proportion of normal estrous cycles was also decreased. These findings indicate irregularities in the estrous cycle. CONCLUSION: Endocrine-disrupting chemicals in corncob bedding might be associated with time to first estrus and length of the estrous cycle. Therefore, the type of bedding should be considered as a factor affecting pubertal progression in rodents.

Estrogen receptor alpha polymorphism in boys with constitutional delay of growth and puberty

PURPOSE: There were a lot of reports regarding associations of polymorphisms in the estrogen receptor alpha (ESR1). with many disorders. But, those with constitutional delay of growth and puberty (CDGP) are not known. Our aim is to find out any association between CDGP and ESR1. METHODS: In a total of 27 subjects, we compared 7 CDGP patients with 20 healthy controls with their heights and sexual maturity rates were within normal range. We selected three single nucleotide polymorphisms from intron 1 of ESR1 (rs3778609, rs12665044, and rs827421) as candidates, respectively. RESULTS: In genotype analyses, the frequency of G/G genotype at rs827421 in intron 1 of ESR1 was increased in CDGP boys (P=0.03). CONCLUSION: The genetic variation of ESR1 can be a contributing factor of tempo of growth and puberty.

Estrogen receptor alpha polymorphism in boys with constitutional delay of growth and puberty

PURPOSE: There were a lot of reports regarding associations of polymorphisms in the estrogen receptor alpha (ESR1). with many disorders. But, those with constitutional delay of growth and puberty (CDGP) are not known. Our aim is to find out any association between CDGP and ESR1. METHODS: In a total of 27 subjects, we compared 7 CDGP patients with 20 healthy controls with their heights and sexual maturity rates were within normal range. We selected three single nucleotide polymorphisms from intron 1 of ESR1 (rs3778609, rs12665044, and rs827421) as candidates, respectively. RESULTS: In genotype analyses, the frequency of G/G genotype at rs827421 in intron 1 of ESR1 was increased in CDGP boys (P=0.03). CONCLUSION: The genetic variation of ESR1 can be a contributing factor of tempo of growth and puberty.

Birth statistics of high birth weight infants (macrosomia) in Korea / 소아과

PURPOSE: The authors analyzed the trend from the birth-related statistics of high birth weight infants (HBWIs) over 50 years in Korea from 1960 to 2010. METHODS: We used 2 data sources, namely, the hospital units (1960's to 1990's) and Statistics Korea (1993 to 2010). The analyses include the incidence of HBWIs, birth weight distribution, sex ratio, and the relationship of HBWI to maternal age. RESULTS: The hospital unit data indicated the incidence of HBWI as 3 to 7% in the 1960's and 1970's and 4 to 7% in the 1980's and 1990's. Data from Statistics Korea indicated the percentages of HBWIs among total live births decreased over the years: 6.7% (1993), 6.3% (1995), 5.1% (2000), 4.5% (2000), and 3.5% (2010). In HBWIs, the birth weight rages and percentage of incidence in infants' were 4.0 to 4.4 kg (90.3%), 4.5 to 4.9 kg (8.8%), 5.0 to 5.4 kg (0.8%), 5.5 to 5.9 kg (0.1%), and >6.0 kg (0.0%) in 2000 but were 92.2%, 7.2%, 0.6%, 0.0%, and 0.0% in 2009. The male to female ratio of HBWIs was 1.89 in 1993 and 1.84 in 2010. In 2010, the mother's age distribution correlated with low (4.9%), normal (91.0%), and high birth weights (3.6%): an increase in mother's age resulted in an increase in the frequency of low birth weight infants (LBWIs) and HBWIs. CONCLUSION: The incidence of HBWIs for the past 50 years has been dropping in Korea. The older the mother, the higher was the risk of a HBWI and LBWI. We hope that these findings would be utilized as basic data that will aid those managing HBWIs.

Regional Analysis on the Incidence of Preterm and Low Birth Weight Infant and the Current Situation on the Neonatal Intensive Care Units in Korea, 2009

PURPOSE: Recently, the incidence of preterm and low birth weight infants (LBWI) is increasing, even though the birth rate is continuously low in Korea. Despite that change, there continues to be a deficit of beds in the neonatal intensive care unit (NICU). This study is based on the 2009 Korean Statistical Information Service that examined the development of a Korean NICU service and the survival rate of preterm infants by regionally analyzing the rate of total live births, preterm infants, LBWI, and NICU beds in Korea. METHODS: Data were obtained from the Korean Health Insurance Review and Assessment Service and Korean Statistical Information Service. We confirmed the regional total live birth rate, number of LBWI, and preterm infants and NICU numbers, and all of the results were compared to the average value to determine deficient areas of NICU beds. RESULTS: There were 25,374 (5.7%) preterm infants and 21,954 (4.9%) LBWI in the total number of live births (444,849) in 2009, and regions of high proportion compared to the mean value were Busan, Daegu, and Ulsan. Total NICU beds totaled 1,284, and regions of high rates preterm infants and LBWI per 1 NICU bed compared to the mean value were Incheon, Daegu, Ulsan, etc. The NICU holding rate was 87.5% (1,284/1,468), which was increased from 2005. However, there were still shortages of 184 NICU beds (12.5%), especially in Gyeonggi-do, which lacked 157 beds. CONCLUSION: High risk neonates difficult to transfer, and they need immediate and continuous treatment. As a result, a foundation of well-balanced, national NICU regionalization is necessary. This study suggested that more NICU facilities must be implemented, and clinicians should realize the continuing deficiency of NICU beds in cities and provinces.