Hum. Reprod. Advance Access originally published online on March 21, 2007
Human Reproduction 2007 22(6):1789-1794; doi:10.1093/humrep/dem052
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Polymorphism in the insulin-like growth factor 1 gene is associated with age at menarche in caucasian females
1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China 2 Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, NE 68131, USA 3 Department of Orthopedic Surgery, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
4 To whom correspondence should be addressed at: School of Medicine, Department of Basic Medical Science, University of Missouri/Kansas City, Room: M3-CO3, 2411 Holmes Street, Kansas City, MO 64108-2792, USA. Tel: +816-235-5354, Fax: +816-235-6517, E-mail: dengh{at}umkc.edu
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Abstract |
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BACKGROUND: The insulin-like growth factor 1 (IGF1) gene, which plays a crucial role in hypothalamic–pituitary–ovarian hormone-controlled metabolic processes, may influence the onset of menarche. Our study aimed to test association between IGF1 polymorphisms with the variation of age at menarche (AAM) in Caucasian females.
METHODS: We recruited a sample of 1048 females from 354 Caucasian nuclear families and genotyped 19 single-nucleotide polymorphisms (SNPs) spanning the entire IGF1 gene. Pairwise linkage disequilibrium among SNPs was measured, and the haplotype blocks were inferred. Both single SNP markers and haplotypes were tested for association with AAM using the quantitative transmission disequilibrium test.
RESULTS: Significant association (P = 0.0153) between AAM and SNP3 (rs6214) in block1 was detected.
CONCLUSIONS: Our results suggested a potential effect of SNP3 in the IGF1 gene on AAM variation in Caucasian women for the first time. However, further independent studies are needed to confirm our findings.
Key words: association/insulin-like growth factor 1/age at menarche/haplotype
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Introduction |
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Menarche, the beginning of menstruation, is the cornerstone in women's lives (Ku et al., 2006
). Early menarche is associated with elevated risk of ovarian tumors and breast cancer (Geschwind and Galaburda, 1985; Trichopoulos, 1990). Delayed menarche may increase the risk of osteoporosis (Eastell, 2005). Thus, it is valuable and necessary to explore the potential factors influencing the variation of age at menarche (AAM).
AAM is determined by different environmental and genetic factors(van Noord et al., 1997; Worda et al., 2004). It was reported that 53–74% of the variation in AAM could be due to genetic effects (Kaprio et al., 1995; Sharma, 2002). For example genetic linkage and association studies have suggested several quantitative trait loci (Guo et al., 2006) and candidate genes for AAM (Gorai et al., 2003; Xita et al., 2005). However, these findings only partly explain the genetic architecture underlying AAM variation, and more AAM-influencing genetic factors wait to be found.
Insulin-like growth factor 1 (IGF1) plays a crucial role in hypothalamic–pituitary–ovarian hormone-controlled metabolic processes (Jones and Clemmons, 1995) and is the major effector of bone growth (Khosla, 1997; Kawai et al., 1999). It is known that GnRH is the key regulator of the reproductive system, directly regulating the release of LH and FSH that are essential for the normal function of the gonads (Chandrashekar and Bartke, 2003). Hypothalamic GnRH mRNA expression increased at 3.5 months and declined by 6 months of age during puberty in the gilt (Barb et al., 2006). The increment in IGF1 might be involved in the stimulation of GnRH activity in the normal children (Belgorosky and Rivarola, 1998). Furthermore, previous studies have shown that IGF1 is a metabolic signal capable of activating the GnRH/LH-releasing system at the time of puberty in rats (Hiney et al., 1991) and IGF1 is capable of enhancing FSH-stimulated LH receptor expression (Adashi et al., 1985c). IGF1 and FSH can synergize to stimulate progesterone production in primary cultures of maturing human granulosa cells (LaVoie et al., 1999). IGF1 also enhances FSH-mediated steroidogenesis, including estradiol (E2) and progesterone production (Bergh et al., 1991 Adashi et al., 1985a; Veldhuis and Demers, 1985; Veldhuis and Rodgers, 1987; Erickson et al., 1989, 1991). All of these findings suggest that the IGF1 may play significant roles in pubertal development, menarche, the menstrual cycle, fertility and reproduction system (Hiney et al., 1996; Huang et al., 1998; Spiliotis, 2003). Menarche depends on the maturation of female reproductive system. Early Menarche is associated with early onset of ovulatory cycles (Hickey and Balen, 2003). It has been reported that hypothalamic–pituitary–ovarian axis controls the age of first ovulation and occurrence of menarche (Beitins, 1981; Hickey and Balen, 2003; Loucks, 2006). It is therefore possible that IGF1 may have an effect on the onset of menarche.
Based on this hypothesis, we tested IGF1 gene single nucleotide polymorphisms (SNPs) comprehensively for an association with AAM variation using the quantitative transmission disequilibrium test (QTDT) in a large sample of Caucasian females.
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Materials and Methods |
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Subjects
This study was approved by the Creighton University Institutional Review Board. Signed informed-consent documents were obtained from all participants before they entered the study. Women with chronic diseases and conditions that might potentially affect bone mass, structure, or metabolism were excluded. These diseases/conditions included chronic disorders involving vital organs (heart, lung, liver, kidney and brain), serious metabolic diseases (diabetes, hypo- and hyper-parathyroidism, hyperthyroidism, etc.), other skeletal diseases (Paget disease, osteogenesis imperfecta, rheumatoid arthritis, etc.), chronic use of drugs affecting bone metabolism (hormone replacement therapy, corticosteroid therapy and anti-convulsant drugs) and malnutrition conditions (such as chronic diarrhea, chronic ulcerative colitis, etc.). Initially, all of the 1873 participants from 405 nuclear families were US Caucasians of European origin recruited for complex diseases or traits research. For menarche study, we selected families that contain at least two informative female subjects (
1 daughters) with AAM data. Therefore, 50 families having only male offspring and 1 family without enough AAM data for daughters were excluded. At last, 1051 female subjects from 354 nuclear families were studied, with the ages ranging from 19 to 85 years old.
AAM data
For each study subject, the detailed medical information including menstrual history was recorded by nurse-administered questionnaire. AAM was calculated as the date of menarche following the onset of menses minus the date of birth (in years rounded to the first decimal place. After excluding three outliers whose AAM were 18 years or older (diagnosed as primary amenorrhea), our AAM data followed normal distribution as verified by the Kolmogorov–Smirnov test implemented in the software Minitab (Minitab, Inc., State College, PA, USA). The final sample used in the association analysis consisted of 1048 females and their AAM ranged from 8.5 to 17.0 years with a mean of 13.0 (SD = 1.4).
SNP selection and genotyping
A total of 19 SNPs in and around IGF1 gene were selected on the basis of the following criteria: (i) validation status, namely, SNPs we selected exist in Caucasian, (ii) an average density of 1 SNP per 4 kb, (iii) degree of heterozygosity, i.e. minor allele frequencies (MAF) > 0.05, (iv) functional relevance and importance and (v) reported to SNP database by various sources. Genomic DNA was extracted from whole blood using a commercial isolation kit (Gentra Systems, Minneapolis, MN, USA) following the procedure detailed in the kit. DNA concentration was assessed by a DU530 UV/VIS spectrophotometer (Beckman Coulter, Inc., Fullerton, CA, USA). All the subjects were genotyped, yielding a large set of genotype data that are further subject to Mendelian inheritance checking, allele frequency estimation and haplotype reconstruction. Nineteen SNPs were successfully genotyped using the high-throughput BeadArray SNP genotyping technology of Illumina Inc (San Diego, CA, USA). The average rate of missing genotype data was reported by Illumina to be 
0.05%. The average genotyping error rate estimated through blind duplicating was reported to be less than 0.01%. The nineteen SNPs were spaced 85 kb apart on average and covered the full transcript length of the IGF1 gene.
Statistical analysis
PedCheck (O'Connell and Weeks, 1998) was used to check Mendelian consistency of SNP genotype data and any inconsistent genotypes were removed. Then the error checking option embedded in Merlin (Abecasis et al., 2002) was run to identify and disregard the genotypes flanking excessive recombinants, thus further reducing genotyping errors. Allele frequencies for each SNP were calculated by allele counting, and the Hardy–Weinberg equilibrium was tested using the PEDSTATS procedure embedded in Merlin. Population haplotypes and their frequencies were inferred for each of the nineteen genes using PHASE v2.1.1 software among 703 unrelated parents. Linkage disequilibrium (LD) structure for each gene was defined, using GOLD (http://www.sph.umich.edu/csg/abecasis/GOLD/), to chart pairwise D' statistics derived from haplotype data. HaploBlockFinder (http://cgi.uc.edu/cgi-bin/kzhang/haploBlockFinder.cgi/) was used to identify block structures and select haplotype-tagging SNPs (htSNPs) of each candidate gene. To infer haplotypes defined by the tagging SNPs within each block of the gene for all of the subjects among 405 families, we adopted the algorithm of integer linear programming implemented in PedPhase V2.0 (http://www.cs.ucr.edu/~jili/haplotyping.html), which is based on LD assumption and able to recover phase information at each marker locus with great speed and accuracy even in the presence of 20% missing data (Li and Jiang, 2005). The QTDT software (http://www.sph.umich.edu/csg/abecasis/QTDT/) (Allison, 1997; Abecasis et al., 2000) was used to test each SNP and haplotype with estimated frequencies > 5% for association with AAM variation. Using QTDT, we also performed 1000 permutations to adjust for the potential multiple-testing problem.
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Results |
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Allele frequencies, LD and haplotype reconstruction
The information of all the IGF1 SNPs is summarized in (Table 1). The MAFs of these SNPs ranged from 0.06 to 0.41. All the SNPs were in Hardy–Weinberg equilibrium (P > 0.01). LD block structure of IGF1 is shown in Figure 1. We identified three significant LD blocks, with the sizes of 13.6, 53.9 and 17.3 kb, respectively. Block 1 ranged from the 3' untranslated region to exon4 with SNP2 and SNP3 selected as htSNPs. Block 2 extended from intron3 to intron2 with SNP4 and SNP13 selected as htSNPs. Block 3 covered from intron2 to the promoter region with SNP16, SNP17 and SNP19 selected as htSNPs. SNP15 and rs5742629 had no strong LD with any other SNPs and thus cannot be assigned to any of the three blocks. The detailed information for blocks is presented in (Table 2).
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QTDT analyses
Table 3 summarizes association results of IGF1 gene with AAM in nuclear families by QTDT. We tested all htSNPs and haplotypes for association with AAM. We did not find any evidence of population stratification for either single SNP markers or haplotypes. For single locus analysis, we detected significant association for SNP3 (P = 0.0153), which lies in block 1. We also detected evidence of association with AAM for haplotype GA (P = 0.0243) in block 1. These two associations both reached the permutation-established experiment-significance level of
= 0.026. Thus the association evidence matched at both the single SNP and haplotype levels. We further assessed the effect of different haplotypes in block 1 on AAM. The mean AAM for subjects carrying the GA haplotype in block 1 is 13.13 years (SD = 1.44), and for the non-carriers it is 12.86 years (SD = 1.39) (P = 0.0243).
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Discussion |
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Our study is the first to suggest that IGF1 may associate with the variation of AAM. The protein encoded by the IGF1 gene is involved in the biosynthesis of ovarian hormones and present in many tissues to control cell differentiation, proliferation and apoptosis. It has been proposed that IGF1 functions as an autocrine/paracrine regulator of ovary development. The IGF system plays a role in the formation of the ovary and ovum and participates in the regulation of bone metabolism (Libanati et al., 1999
). In this study, we found the significant associations with AAM for SNP3 and the haplotype GA reconstructed by the htSNPs (SNP3 and SNP4). SNP3 (rs6214) is located in exon4, and although itself does not cause any amino acid change, it may be in strong LD with certain functional variants influencing the mRNA splicing of IGF1, or alternatively, with certain functional alleles of exon4 changing the amino acid sequence of IGF1 protein. However, all of the above are just hypotheses and wait to be tested by further functional analyses.
In females, different kinds of hormones, growth factors and cytokines are involved in the onset of menarche (Tamura et al., 1998; Behl and Kaul, 2002; Bornstein et al., 2004; Quirk et al., 2004). Lots of evidence showed that the IGF1 system plays a key role in ovarian folliculogenesis (Adashi et al., 1985b; Giudice, 1992). In vivo levels of IGF1 (Cook et al., 1993) and IGF1 binding protein (IGFBP3) are positively correlated with the serum E2 concentration in girls during puberty (Suter et al., 2000; Blogowska et al., 2003; Kanbur-Oksuz et al., 2004; Kulik-Rechberger and Janiszewska, 2004). More interestingly, there is a higher positive correlation between plasma E2 and IGF1/IGFBP3 ratio, an index of free IGF1. There is a positive correlation between LH and FSH with both IGF1 and IGFBP3, and FSH and LH stimulate some isoform of hepatic IGF1 mRNA (Ruiz et al., 2001). Concurrent treatment with increasing concentrations of IGF1 brought about dose-dependent increases in FSH-induced LH receptor mRNA, a response which was 2.5-fold greater than that induced by FSH alone at the highest concentration in rat granulosa cells (Hirakawa et al., 1999). On average, the production of E2 was 2.8-fold higher when polycystic ovary disease granulosa cells were treated concomitantly with FSH and IGF1 than that evoked only by FSH (Erickson et al., 1990). In all, these biological and physiological studies lend support to our finding that the IGF1 gene polymorphisms influence the variation of AAM.
Our study has several notable strengths. First, our sample is relatively large, which includes 1048 females from 354 Caucasian nuclear families. Therefore, adequate statistical power is guaranteed to find the genetic variants of modest effect sizes on the AAM variation. Second, we selected 19 SNPs distributed throughout the IGF1 gene to test for its association with AAM, rather than just testing only a few SNPs in the gene. These SNPs comprehensively covered the entire IGF gene. Third, we adopted the family-based association analysis to obviate the known population stratification problem in the European American population. All of these approaches made this study a robust and reliable one for the follow-up research.
We estimated the power of our study using the Program Genetic Power Calculator (GPC, http://statgen.iop.kcl.ac.uk/gpc/qtlassoc.html). Under the condition of the conservative significance level of 0.001 and the strong LD of |D'| = 0.9, our sample can achieve 90% power to detect the causal variants responsible for 4% variation of AAM.
In general, AAM is acquired by recall and self-reports, which may increase the likelihood of error. However, study suggests a high correction of 0.79 between recalled and actual AAM and it is also found that recall of AAM was generally quite good, both in precision and accuracy (Must et al., 2002). AAM was recalled to within 1 year of the actual event by 84% of the females (Casey et al., 1991). The accuracy of recall of AAM was confirmed further in other previously studies (Bergsten-Brucefors 1976; Bean et al., 1979; Greif and Ulman, 1982; Koo and Rohan, 1997) In addition, study found that important personal experiences can produce clear memories of a person's circumstance at the time of the event, that is ‘flashbulb memories’ (Pillemer et al., 1987), and menarche was such a significant developmental event that almost all of the women remembered the date of their first menstruation (Golub and Catalano, 1983). Therefore, recalled measures and self-reports should be quite valid to obtain AAM.
In conclusion, our present study does support the hypothesis that IGF1 variants can influence the onset age of menarche in Caucasians, especially in the European Americans. However, the causal functional variants underlying the observed associations are still unknown. Replication of our results and functional studies are necessary to unravel the true associated variants and the corresponding molecular mechanisms.
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Acknowledgement |
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Investigators of this work were partially supported by grants from NIH (R01 AR050496, K01 AR02170-01, R01 AR45349-01, and R01 GM60402-01A1) and an LB595 grant from the State of Nebraska. The study also benefited from grants from Project 30570875 supported by National Natural Science Foundation of China, Xi'an Jiaotong University, and the Ministry of Education of China.
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Footnotes |
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* These authors contributed equally to this work.
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References |
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Abecasis GR, Cardon LR, Cookson WO. (2000) A general test of association for quantitative traits in nuclear families. Am J Hum Genet 66:279–92.[CrossRef][Web of Science][Medline]
Abecasis GR, Cherny SS, Cookson WO, et al. (2002) Merlin–rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97–101.[CrossRef][Web of Science][Medline]
Adashi EY, Resnick CE, Brodie AM, et al. (1985a) Somatomedin-C-mediated potentiation of follicle-stimulating hormone-induced aromatase activity of cultured rat granulosa cells. Endocrinology 117:2313–20.
Adashi EY, Resnick CE, D'Ercole AJ, et al. (1985b) Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocr Rev 6:400–20.
Adashi EY, Resnick CE, Svoboda ME, et al. (1985c) Somatomedin-C enhances induction of luteinizing hormone receptors by follicle-stimulating hormone in cultured rat granulosa cells. Endocrinology 116:2369–75.
Allison DB. (1997) Transmission-disequilibrium tests for quantitative traits. Am J Hum Genet 60:676–90.[Web of Science][Medline]
Barb CR, Hausman GJ, Rekaya R. (2006) Gene expression in the brain-pituitary adipose tissue axis and luteinising hormone secretion during pubertal development in the gilt. Reprod Suppl 62:33–44.[Medline]
Bean JA, Leeper JD, Wallace RB, et al. (1979) Variations in the reporting of menstrual histories. Am J Epidemiol 109:181–5.
Behl R and Kaul R. (2002) Insulin like growth factor 1 and regulation of ovarian function in mammals. Indian J Exp Biol 40:25–30.[Medline]
Beitins IZ. (1981) Menstrual abnormalities during adolescence. Prim Care 8:3–18.[Medline]
Belgorosky A and Rivarola MA. (1998) Irreversible increase of serum IGF-1 and IGFBP-3 levels in GnRH-dependent precocious puberty of different etiologies: implications for the onset of puberty. Horm Res 49:226–32.[CrossRef][Web of Science][Medline]
Bergh C, Olsson JH, Hillensjo T. (1991) Effect of insulin-like growth factor I on steroidogenesis in cultured human granulosa cells. Acta Endocrinol (Copenh) 125:177–85.
Bergsten-Brucefors A. (1976) A note on the accuracy of recalled age at menarche. Ann Hum Biol 3:71–3.[CrossRef][Web of Science][Medline]
Blogowska A, Rzepka-Gorska I, Krzyzanowska-Swiniarska B. (2003) Growth hormone, IGF-1, insulin, SHBG, and estradiol levels in girls before menarche. Arch Gynecol Obstet 268:293–6.[CrossRef][Medline]
Bornstein SR, Rutkowski H, Vrezas I. (2004) Cytokines and steroidogenesis. Mol Cell Endocrinol 215:135–41.[CrossRef][Web of Science][Medline]
Casey VA, Dwyer JT, Coleman KA, et al. (1991) Accuracy of recall by middle-aged participants in a longitudinal study of their body size and indices of maturation earlier in life. Ann Hum Biol 18:155–66.[CrossRef][Web of Science][Medline]
Chandrashekar V and Bartke A. (2003) The role of insulin-like growth factor-I in neuroendocrine function and the consequent effects on sexual maturation: inferences from animal models. Reprod Biol 3:7–28.[Medline]
Cook JS, Hoffman RP, Stene MA, et al. (1993) Effects of maturational stage on insulin sensitivity during puberty. J Clin Endocrinol Metab 77:725–30.[Abstract]
Eastell R. (2005) Role of oestrogen in the regulation of bone turnover at the menarche. J Endocrinol 185:223–34.
Erickson GF, Garzo VG, Magoffin DA. (1989) Insulin-like growth factor-I regulates aromatase activity in human granulosa and granulosa luteal cells. J Clin Endocrinol Metab 69:716–24.
Erickson GF, Garzo VG, Magoffin DA. (1991) Progesterone production by human granulosa cells cultured in serum free medium: effects of gonadotrophins and insulin-like growth factor I (IGF-I). Hum Reprod 6:1074–81.
Erickson GF, Magoffin DA, Cragun JR, et al. (1990) The effects of insulin and insulin-like growth factors-I and -II on estradiol production by granulosa cells of polycystic ovaries. J Clin Endocrinol Metab 70:894–902.
Geschwind N and Galaburda AM. (1985) Cerebral lateralization. Biological mechanisms, associations, and pathology: I. A hypothesis and a program for research. Arch Neurol 42:428–59.
Giudice LC. (1992) Insulin-like growth factors and ovarian follicular development. Endocr Rev 13:641–69.
Golub S and Catalano J. (1983) Recollections of menarche and women's subsequent experiences with menstruation. Women Health 8:49–61.[CrossRef][Web of Science][Medline]
Gorai I, Tanaka K, Inada M, et al. (2003) Estrogen-metabolizing gene polymorphisms, but not estrogen receptor-alpha gene polymorphisms, are associated with the onset of menarche in healthy postmenopausal Japanese women. J Clin Endocrinol Metab 88:799–803.
Greif EB and Ulman KJ. (1982) The psychological impact of menarche on early adolescent females: a review of the literature. Child Dev 53:1413–30.[CrossRef][Web of Science][Medline]
Guo Y, Shen H, Xiao P, et al. (2006) Genomewide linkage scan for quantitative trait loci underlying variation in age at menarche. J Clin Endocrinol Metab 91:1009–14.
Hickey M and Balen A. (2003) Menstrual disorders in adolescence: investigation and management. Hum Reprod Update 9:493–504.
Hiney JK, Ojeda SR, Dees WL. (1991) Insulin-like growth factor I: a possible metabolic signal involved in the regulation of female puberty. Neuroendocrinology 54:420–3.[Web of Science][Medline]
Hiney JK, Srivastava V, Nyberg CL, et al. (1996) Insulin-like growth factor I of peripheral origin acts centrally to accelerate the initiation of female puberty. Endocrinology 137:3717–28.[Abstract]
Hirakawa T, Minegishi T, Abe K, et al. (1999) A role of insulin-like growth factor I in luteinizing hormone receptor expression in granulosa cells. Endocrinology 140:4965–71.
Huang YS, Rousseau K, Le Belle N, et al. (1998) Insulin-like growth factor-I stimulates gonadotrophin production from eel pituitary cells: a possible metabolic signal for induction of puberty. J Endocrinol 159:43–52.[Abstract]
Jones JI and Clemmons DR. (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3–34.
Kanbur-Oksuz N, Derman O, Kinik E. (2004) Correlation of sex steroids with IGF-1 and IGFBP-3 during different pubertal stages. Turk J Pediatr 46:315–21.[Web of Science][Medline]
Kaprio J, Rimpela A, Winter T, et al. (1995) Common genetic influences on BMI and age at menarche. Hum Biol 67:739–53.[Web of Science][Medline]
Kawai N, Kanzaki S, Takano-Watou S, et al. (1999) Serum free insulin-like growth factor I (IGF-I), total IGF-I, and IGF-binding protein-3 concentrations in normal children and children with growth hormone deficiency. J Clin Endocrinol Metab 84:82–9.
Khosla S. (1997) Idiopathic osteoporosis–is the osteoblast to blame? J Clin Endocrinol Metab 82:2792–4.
Koo MM and Rohan TE. (1997) Accuracy of short-term recall of age at menarche. Ann Hum Biol 24:61–4.[CrossRef][Web of Science][Medline]
Ku SY, Kang JW, Kim H, et al. (2006) Age at menarche and its influencing factors in North Korean female refugees. Hum Reprod 21:833–6.
Kulik-Rechberger B and Janiszewska O. (2004) Insulin-like growth factor 1, its binding protein 3, and sex hormones in girls during puberty. Ann Univ Mariae Curie Sklodowska [Med ] 59:75–9.[Medline]
LaVoie HA, Garmey JC, Veldhuis JD. (1999) Mechanisms of insulin-like growth factor I augmentation of follicle-stimulating hormone-induced porcine steroidogenic acute regulatory protein gene promoter activity in granulosa cells. Endocrinology 140:146–53.
Li J and Jiang T. (2005) Computing the minimum recombinant haplotype configuration from incomplete genotype data on a pedigree by integer linear programming. J Comput Biol 12:719–39.[CrossRef][Web of Science][Medline]
Libanati C, Baylink DJ, Lois-Wenzel E, et al. (1999) Studies on the potential mediators of skeletal changes occurring during puberty in girls. J Clin Endocrinol Metab 84:2807–14.
Loucks AB. (2006) The response of luteinizing hormone pulsatility to 5 days of low energy availability disappears by 14 years of gynecological age. J Clin Endocrinol Metab 91:3158–64.
Must A, Phillips SM, Naumova EN, et al. (2002) Recall of early menstrual history and menarcheal body size: after 30 years, how well do women remember? Am J Epidemiol 155:672–9.
Pillemer DB, Koff E, Rhinehart ED, et al. (1987) Flashbulb memories of menarche and adult menstrual distress. J Adolesc 10:187–99.[Web of Science][Medline]
Quirk SM, Cowan RG, Harman RM, et al. (2004) Ovarian follicular growth and atresia: the relationship between cell proliferation and survival. J Anim Sci 82:E40–E52.
Ruiz E, Osorio A, Torres JM, et al. (2001) Evidence of different actions of testosterone estradiol, FSH, and LH on the growth axis. Endocr Res 27:25–33.[CrossRef][Web of Science][Medline]
Sharma K. (2001) Genetic basis of human female pelvic morphology: a twin study. Am J Phys Anthropol 117:327–33.[Web of Science]
Spiliotis BE. (2003) Growth hormone insufficiency and its impact on ovarian function. Ann N Y Acad Sci 997:77–84.[CrossRef][Web of Science][Medline]
Suter KJ, Pohl CR, Wilson ME. (2000) Circulating concentrations of nocturnal leptin, growth hormone, and insulin-like growth factor-I increase before the onset of puberty in agonadal male monkeys: potential signals for the initiation of puberty. J Clin Endocrinol Metab 85:808–14.
Tamura K, Tamura H, Kumasaka K, et al. (1998) Ovarian immune cells express granulocyte-macrophage colony-stimulating factor (GM-CSF) during follicular growth and luteinization in gonadotropin-primed immature rodents. Mol Cell Endocrinol 142:153–63.[CrossRef][Web of Science][Medline]
Trichopoulos D. (1990) Hypothesis: does breast cancer originate in utero? Lancet 335:939–40.[CrossRef][Web of Science][Medline]
van Noord PA, Dubas JS, Dorland M, et al. (1997) Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors. Fertil Steril 68:95–102.[CrossRef][Web of Science][Medline]
Veldhuis JD and Demers LM. (1985) A role for somatomedin C as a differentiating hormone and amplifier of hormone action on ovarian cells: studies with synthetically pure human somatomedin C and swine granulosa cells. Biochem Biophys Res Commun 130:234–40.[CrossRef][Web of Science][Medline]
Veldhuis JD and Rodgers RJ. (1987) Mechanisms subserving the steroidogenic synergism between follicle-stimulating hormone and insulin-like growth factor I (somatomedin C). Alterations in cellular sterol metabolism in swine granulosa cells. J Biol Chem 262:7658–64.
Worda C, Walch K, Sator M, et al. (2004) The influence of Nos3 polymorphisms on age at menarche and natural menopause. Maturitas 49:157–62.[CrossRef][Web of Science][Medline]
Xita N, Tsatsoulis A, Stavrou I, et al. (2005) Association of SHBG gene polymorphism with menarche. Mol Hum Reprod 11:459–62.
Submitted on August 10, 2006; resubmitted on October 27, 2006; resubmitted on December 22, 2006; accepted on January 2, 2007.
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