Up-To-Date Review About Minipuberty and Overview on Hypothalamic-Pituitary-Gonadal Axis Activation in Fetal and Neonatal Life

Lucia Lanciotti, Marta Cofini, Alberto Leonardi, Laura Penta, Susanna Esposito, Lucia Lanciotti, Marta Cofini, Alberto Leonardi, Laura Penta, Susanna Esposito

Abstract

Minipuberty consists of activation of the hypothalamic-pituitary-gonadal (HPG) axis during the neonatal period, resulting in high gonadotropin and sex steroid levels, and occurs mainly in the first 3-6 months of life in both sexes. The rise in the levels of these hormones allows for the maturation of the sexual organs. In boys, the peak testosterone level is associated with penile and testicular growth and the proliferation of gonadic cells. In girls, the oestradiol levels stimulate breast tissue, but exhibit considerable fluctuations that probably reflect the cycles of maturation and atrophy of the ovarian follicles. Minipuberty allows for the development of the genital organs and creates the basis for future fertility, but further studies are necessary to understand its exact role, especially in girls. Nevertheless, no scientific study has yet elucidated how the HPG axis turns itself off and remains dormant until puberty. Additional future studies may identify clinical implications of minipuberty in selected cohorts of patients, such as premature and small for gestational age infants. Finally, minipuberty provides a fundamental 6-month window of the possibility of making early diagnoses in patients with suspected sexual reproductive disorders to enable the prompt initiation of treatment rather than delaying treatment until pubertal failure.

Keywords: gonadotropin; hypothalamic-pituitary-gonadal; minipuberty; oestradiol; testosterone.

Figures

Figure 1
Figure 1
Patterns of fetal and postnatal luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) secretion in males.
Figure 2
Figure 2
Patterns of fetal and postnatal luteinizing hormone (LH), follicle stimulating hormone (FSH) and oestradiol secretion in females.

References

    1. Forest MG, Cathiard AM. Pattern of plasma testosterone and A4 androstenedione in normal newborns: evidence for testicular activity at birth. J Clin Endocrinol Metab. (1975) 1:977–80. 10.1210/jcem-41-5-977
    1. Forest MG, Cathiard AM, Bertrand JA. Evidence of testicular activity in early infncy. J Clin Endocrinol Metab. (1973) 1:148–51. 10.1210/jcem-37-1-148
    1. Schwanzel-Fukada M, Pfaff D. Origin of luteinizing hormone-releasing hormone neurons. Nature (1989) 338:161–4. 10.1038/338161a0
    1. Crossin KL, Pfaff DW, Bouloux PMG, Pasteur I, France JH. Migration of luteinizing hormone-releasing hormone (LHRH) neurons in early human embryos. J Clin Invest. (1996) 1996:547657.
    1. Hagen C, McNeilly AS. The gonadotrophins and their subunits in foetal pituitary glands and circulation. J Steroid Biochem. (1977) 8:537–44. 10.1016/0022-4731(77)90259-X
    1. Clements JA, Reyes FI, Winter JSD, Faiman C. Studies on human sexual development. III. Fetal pituitary and serum, and amniotic fluid concentrations of LH, CG, and FSH. J Clin Endocrinol Metab. (1976) 42:9. 10.1210/jcem-42-1-9
    1. Guimiot F, Chevrier L, Dreux S, Chevenne D, Caraty A, Delezoide AL, et al. . Negative fetal FSH/LH regulation in late pregnancy is associated with declined Kisspeptin/KISS1R expression in the tuberal hypothalamus. J Clin Endocrinol Metab. (2012) 97:2221–9. 10.1210/jc.2012-2078
    1. Takagi S, Yoshida T, Tsubata K, Ozaki H, Fujii TK, Nomura Y, et al. . Sex differences in fetal gonadotropins and androgens. J Steroid Biochem. (1977) 8:609–20. 10.1016/0022-4731(77)90270-9
    1. Massa G, de Zegher F, Vanderschueren-Lodeweyckx M. Serum levels of immunoreactive inhibin, FSH, and LH in human infants at preterm and term birth. Biol Neonate. (1992) 61:150–5. 10.1159/000243737
    1. Troisi R, Potischman N, Roberts JM, Harger G, Markovic N, Cole B, et al. Hoover RN. Correlation of serum hormone concentrations in maternal and umbilical cord samples. Cancer Epidemiol Biomarkers Prev. (2003) 12:452–6.
    1. Kaplan SL, Grumbach MM. The ontogenesis of human foetal hormones. II. Luteinizing hormone (LH) and follicle stimulating hormone (FSH). Acta Endocrinol. (1976) 81:808–29. 10.1530/acta.0.0810808
    1. Debieve F, Beerlandt S, Hubinont C, Thomas K. Gonadotropins, prolactin, inhibin A, inhibin B, and activin A in human fetal serum from midpregnancy and term pregnancy. J Clin Endocrinol Metab. (2000) 85:270–4. 10.1210/jcem.85.1.6249
    1. Winter JS. Hypothalamic-pituitary function in the fetus and infant. Clin Endocrinol Metab. (1982) 11:41–55. 10.1016/S0300-595X(82)80037-6
    1. Reyes FI, Borodits RS, Winter JSD, Faiman C. Studies on human sexual development .2. Fetal and maternal serum gonadotropin and sex steroid concentrations. J Clin Endocrinol Metab. (1974) 38:612–7. 10.1210/jcem-38-4-612
    1. Beck-Peccoz P, Padmanabhan V, Baggiani AM, Cortelazzi D, Buscaglia M, Medri G, et a. Maturation of hypothalamic-pituitary-gonadal function in normal human fetuses: circulating levels of gonadotropins, their common a-subunit and free testosterone, and discrepancy between immunological and biological activities of circulating follicle-stimu. J Clin Endocrinol Metab. (1991) 73:525–32. 10.1210/jcem-73-3-525
    1. Tapanainen J, Kellokumpu-lehtinen P, Pelliniemi L. Age-related changes in endogenous steroids of human. J Clin Endocrinol Metab. (1981) 52:98–102. 10.1210/jcem-52-1-98
    1. Latronico AC, Anasti J, Arnhold IJ, Rapaport R, Mendonca BB, Bloise W, et al. . Testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone. N Engl J Med. (1996) 334:507–12. 10.1056/NEJM199602223340805
    1. Zhang S, Li W, Zhu C, Wang X, Li Z, Zhang J, et al. . Sertoli cell-specific expression of metastasis-associated protein 2 (MTA2) is required for transcriptional regulation of the follicle-stimulating hormone receptor (FSHR) gene during spermatogenesis. J Biol Chem. (2012) 287:40471–83. 10.1074/jbc.M112.383802
    1. Plant TM, Marshall GR. The functional significance of FSH in spermatogenesis and the control of its secretion in male primates. Endocr Rev. (2001) 22:764–86. 10.1210/edrv.22.6.0446
    1. O'Shaughnessy PJ, Baker PJ, Monteiro A, Cassie S, Bhattacharya S, Fowler PA. Developmental changes in human fetal testicular cell numbers and messenger ribonucleic acid levels during the second trimester. J Clin Endocrinol Metab. (2007) 92:4792–801. 10.1210/jc.2007-1690
    1. Bowles J, Koopman P. Sex determination in mammalian germ cells: extrinsic versus intrinsic factors. Reproduction (2010) 139:943–58. 10.1530/REP-10-0075
    1. Forabosco A, Sforza C. Establishment of ovarian reserve: a quantitative morphometric study of the developing human ovary. Fertil Steril. (2007) 88:675–83. 10.1016/j.fertnstert.2006.11.191
    1. Baker TG, Scrimgeour JB. Development of the gonad in normal and anencephalic human fetuses. J Reprod Fertil. (1980) 60:193–9. 10.1530/jrf.0.0600193
    1. Varvarigou AA, Liatsis SG, Vassilakos P, Decavalas G, Beratis NG. Effect of maternal smoking on cord blood estriol, placental lactogen, chorionic gonadotropin, FSH, LH, and cortisol. J Perinat Med. (2009) 37:364–9. 10.1515/JPM.2009.028
    1. Corbier P, Dehennin L, Castanier M, Mebazaa A, Edwards DA, Roffi J. Sex differences in serum luteinizing hormone and testosterone in the human neonate during the first few hours after birth. J Clin Endocrinol Metab. (1990) 71:1344–8. 10.1210/jcem-71-5-1344
    1. de Zegher F, Devlieger H, Veldhuis JD. Pulsatile and sexually dimorphic secretion of luteinizing hormone in the human infant on the day of birth. Pediatr Res. (1992) 32:605–7. 10.1203/00006450-199211000-00025
    1. Schmidt H, Schwarz HP. Serum concentrations of LH and FSH in the healthy newborn. Eur J Endocrinol. (2000) 143:213–5. 10.1530/eje.0.1430213
    1. Bergadá I, Milani C, Bedecarrás P, Andreone L, Ropelato MG, Gottlieb S, et al. . Time course of the serum gonadotropin surge, inhibins, and anti-Müllerian hormone in normal newborn males during the first month of life. J Clin Endocrinol Metab. (2006) 91:4092–8. 10.1210/jc.2006-1079
    1. Winter JSD, Faiman C, Hobson WC, Prasad AV, Reyes FI. Pituitary-gonadal relations in infancy. I. patterns of serum gonadotropin concentrations from birth to four years of age in man and chimpanzee. J Clin Endocrinol Metab. (1975) 40:545–51. 10.1210/jcem-40-4-545
    1. Kuiri-Hänninen T, Seuri R, Tyrväinen E, Turpeinen U, Hämäläinen E, Stenman UH, et al. . Increased activity of the hypothalamic-pituitary-testicular axis in infancy results in increased androgen action in premature boys. J Clin Endocrinol Metab. (2011) 96:98–105. 10.1210/jc.2010-1359
    1. Kuiri-Hänninen T, Kallio S, Seuri R, Tyrväinen E, Liakka A, Tapanainen J, Sankilampi U, Dunkel L. Postnatal developmental changes in the pituitary-ovarian axis in preterm and term infant girls. J Clin Endocrinol Metab. (2011) 96:3432–9. 10.1210/jc.2011-1502
    1. Andersson AM, Toppari J, Haavisto AM, Petersen JH, Simell T, Simell O, et al. . Longitudinal reproductive hormone profiles in infants: Peak of inhibin B levels in infant boys exceeds levels in adult men. J Clin Endocrinol Metab. (1998) 83:675–81. 10.1210/jc.83.2.675
    1. Chemes HE. Infancy is not a quiescent period of testicular development. Int J Androl. (2001) 24:2–7. 10.1046/j.1365-2605.2001.00260.x
    1. Codesal J, Regadera J, Nistal M, Regadera-Sejas J, Paniagua R. Involution of human fetal Leydig cells. An immunohistochemical, ultrastructural and quantitative study. J Anat. (1990) 172:103–14.
    1. Lejeune H, Habert R, Saez JM. Origin, proliferation and differentiation of Leydig cells. J Mol Endocrinol. (1998) 20:1–25. 10.1677/jme.0.0200001
    1. Nistal M, Paniagua R, Regadera J, Santamaria L, Amat P. A quantitative morphological study of human Leydig cells from birth to adulthood. Cell Tissue Res. (1986) 246:229–36. 10.1007/BF00215884
    1. Cortes D, Muller J, Skakkebaek NE. Proliferation of Sertoli cells during development of the human testis assessed by stereological methods. Int J Androl. (1987) 10:589–96. 10.1111/j.1365-2605.1987.tb00358.x
    1. Chemes HE, Rey RA, Nistal M, Regadera J, Musse M, González-Peramato P, et al. . Physiological androgen insensitivity of the fetal, neonatal, and early infantile testis is explained by the ontogeny of the androgen receptor expression in sertoli cells. J Clin Endocrinol Metab. (2008) 93:4408–12. 10.1210/jc.2008-0915
    1. Aksglaede L, Sørensen K, Boas M, Mouritsen A, Hagen CP, Jensen RB, et al. . Changes in anti-mullerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab. (2010) 95:5357–64. 10.1210/jc.2010-1207
    1. Boukari K, Meduri G, Brailly-Tabard S, Guibourdenche J, Ciampi ML, Massin N, et al. . Lack of androgen receptor expression in sertoli cells accounts for the absence of anti-Mullerian hormone repression during early human testis development. J Clin Endocrinol Metab. (2009) 94:1818–25. 10.1210/jc.2008-1909
    1. Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab. (2005) 90:3122–7. 10.1210/jc.2004-2465
    1. Boas M, Boisen KA, Virtanen HE, Kaleva M, Suomi AM, Schmidt IM, et al. . Postnatal penile length and growth rate correlate to serum testosterone levels: a longitudinal study of 1962 normal boys. Eur J Endocrinol. (2006) 154:125–9. 10.1530/eje.1.02066
    1. Kuijper EA, van Kooten J, Verbeke JI, van Rooijen M, Lambalk CB. Ultrasonographically measured testicular volumes in 0- to 6-year-old boys. Hum Reprod. (2008) 23:792–6. 10.1093/humrep/den021
    1. Hadziselimovic F, Hadziselimovic NO, Demougin P, Krey G, Oakeley E. Piwi-pathway alteration induces LINE-1 transposon derepression and infertility development in cryptorchidism. Sex Dev. (2015) 9:98–104. 10.1159/000375351
    1. Hickey M, Hart R, Keelan JA. The relationship between umbilical cord estrogens and perinatal characteristics. Cancer Epidemiol Biomarkers Prev. (2014) 23:946–52. 10.1158/1055-9965.EPI-13-1321
    1. Troisi R, Potischman N, Roberts J, Siiteri P, Daftary A, Sims C, et al. . Associations of maternal and umbilical cord hormone concentrations with maternal, gestational and neonatal factors (United States). Cancer Causes Control (2003) 14:347–55.
    1. Schmidt IM, Chellakooty M, Haavisto AM, Boisen KA, Damgaard IN, Steendahl U, et al. . Gender difference in breast tissue size in infancy: correlation with serum estradiol. Pediatr Res. (2002) 52:682–6. 10.1203/00006450-200211000-00012
    1. Kuiri-Hänninen T, Haanpää M, Turpeinen U. Postnatal ovarian activation has effects in estrogen target tissues in infant girls. J Clin Endocrinol Metab. (2013) 98:4709–16. 10.1210/jc.2013-1677
    1. Chellakooty M, Schmidt IM, Haavisto AM, Boisen KA, Damgaard IN, Mau C, et al. . Inhibin A, inhibin B, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin levels in 473 healthy infant girls. J Clin Endocrinol Metab. (2003) 88:3515–20. 10.1210/jc.2002-021468
    1. Bidlingmaier F, Strom TM, Dorr HG, Eisenmenger W, Knorr D. Estrone and estradiol concentrations in human ovaries, testes, and adrenals during the first two years of life. J Clin Endocrinol Metab. (1987) 65:862–7. 10.1210/jcem-65-5-862
    1. Hagen CP, Aksglaede L, Sørensen K, Main KM, Boas M, Cleemann L, et al. ., Juul A. Serum levels of anti-müllerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 turner syndrome patients. J Clin Endocrinol Metab. (2010) 95:5003–10. 10.1210/jc.2010-0930
    1. Jayasinghe Y, Cha R, Horn-Ommen J, O'Brien P, Simmons PS. Establishment of normative data for the amount of breast tissue present in healthy children up to two years of age. J Pediatr Adolesc Gynecol. (2010) 23:305–11. 10.1016/j.jpag.2010.03.002
    1. Tapanainen J, Koivisto M, Vihko R, Huhtaniemi I. Enhanced activity of the pituitary-gonadal axis in premature human infants. J Clin Endocrinol Metab. (1981) 52:235–8. 10.1210/jcem-52-2-235
    1. Shinkawa O, Furuhashi N, Fukaya T, Suzuki M, Kono H, Tachibana Y. Changes of Serum Gonadotropin Levels and Sex Differences in Premature and Mature Infant during Neonatal Life. J Clin Endocrinol Metab. (1983) 56:1327–31. 10.1210/jcem-56-6-1327
    1. De Jong M, Rotteveel J, Heijboer AC, Cranendonk A, Twisk JWR, Van Weissenbruch MM. Urine gonadotropin and estradiol levels in female very-low-birth-weight infants. Early Hum Dev. (2013) 89:131–5. 10.1016/j.earlhumdev.2012.09.007
    1. Keeling JW, Ozer E, King G, Walker F. Oestrogen receptor alpha in female fetal, infant, and child mammary tissue. J Pathol. (2000) 191:449–51. 10.1002/1096-9896(2000)9999:9999<::AID-PATH661>;2-#
    1. Sedin G, Bergquist C, Lindgren PG. Ovarian hyperstimulation syndrome in preterm infants. Pediatr Res. (1985) 19:548–52. 10.1203/00006450-198506000-00009
    1. Marinkovic M, Rasmussen M, Jones K. Feminizing changes in a prematurely born infant. Clin Pediatr (Phila). (2010) 49:188–9. 10.1177/0009922809337624
    1. Starzyk J, Wojcik M, Wojtys J, Tomasik P, Mitkowska Z, Pietrzyk JJ. Ovarian hyperstimulation syndrome in newborns–a case presentation and literature review. Horm Res. (2009) 71:60–4. 10.1159/000173743
    1. Altuntas N, Turkyilmaz C, Yuce O, Kulali F, Hirfanoglu IM, Onal E, et al. . Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report. J Pediatr Endocrinol Metab. (2014) 27:355–8. 10.1515/jpem-2013-0166
    1. Durst MA, Wicklow B, Narvey M. Atypical case of preterm ovarian hyperstimulation syndrome. BMJ Case Rep. (2017) 1:2017 10.1136/bcr-2016-217517
    1. Vochem M. [Ovarian hyperstimulation syndrome in preterm infants]. Z Geburtshilfe Neonatol. (2002) 206:156–60. 10.1055/s-2002-33669
    1. Gluckman PD, Hanson MA. Living with the past: evolution, development, and patterns of disease. Science. (2004) 305:1733–6. 10.1126/science.1095292
    1. Mericq V, Ong KK, Bazaes R, Peña V, Avila A, Salazar T, et al. . Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children. Diabetologia (2005) 48:2609–14. 10.1007/s00125-005-0036-z
    1. Ibáñez L, de Zegher F. Puberty after prenatal growth restraint. Horm Res. (2006) 65(Suppl. 3):112–115.
    1. Ibanez L, Potau N, Enriquez G, Marcos MV, de Zegher F. Hypergonadotrophinaemia with reduced uterine and ovarian size in women born small-for-gestational-age. Hum Reprod. (2003) 18:1565–9. 10.1093/humrep/deg351
    1. Cicognani A, Alessandroni R, Pasini A, Pirazzoli P, Cassio A, Barbieri E, Cacciari E. Low birth weight for gestational age and subsequent male gonadal function. J Pediatr. (2002) 141:376. 10.1067/mpd.2002.126300
    1. Nagai S, Kawai M, Myowa-Yamakoshi M, Morimoto T, Matsukura T, Heike T. Gonadotropin levels in urine during early postnatal period in small for gestational age preterm male infants with fetal growth restriction. J Perinatol. (2017) 37:843–7. 10.1038/jp.2017.55
    1. Ibáñez L, Valls C, Cols M, Ferrer A, Marcos MV, De Zegher F. Hypersecretion of FSH in infant boys and girls born small for gestational age. J Clin Endocrinol Metab. (2002) 87:1986–8. 10.1210/jcem.87.5.8459
    1. Forest MG, de Peretti E, Bertrand J. Testicular and adrenal androgens and their binding to plasma proteins in the perinatal period: developmental patterns of plasma testosterone, 4-androstenedione, dehydroepiandrosterone and its sulfate in premature and small for date infants as compared wit. J Steroid Biochem. (1980) 12:25–36. 10.1016/0022-4731(80)90247-2
    1. Becker M, Oehler K, Partsch CJ, Ulmen U, Schmutzler R, Cammann H, et al. Hormonal “minipuberty” influences the somatic development of boys but not of girls up to the age of 6 years. Clin Endocrinol. (2015) 83:694–701. 10.1111/cen.12827
    1. Kiviranta P, Kuiri-Hänninen T, Saari A, Lamidi M-L, Dunkel L, Sankilampi U. Transient postnatal gonadal activation and growth velocity in infancy. Pediatrics (2016) 138:e20153561. 10.1542/peds.2015-3561
    1. Quinton R, Mamoojee Y, Jayasena CN, Young J, Howard S, Dunkel L, et al. . Society for Endocrinology UK guidance on the evaluation of suspected disorders of sexual development: emphasizing the opportunity to predict adolescent pubertal failure through a neonatal diagnosis of absent minipuberty. Clin Endocrinol. (2017) 86:305–6. 10.1111/cen.13257
    1. Dwyer AA, Jayasena CN, Quinton R. Congenital hypogonadotropic hypogonadism: implications of absent mini-puberty. Minerva Endocrinol. (2016) 41:188–95.
    1. Bonomi M, Vezzoli V, Krausz C, Guizzardi F, Vezzani S, Simoni M, et al. Italian Network on Central Hypogonadism. Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH). Eur J Endocrinol. (2018) 178:23–32. 10.1530/EJE-17-0065
    1. Koskenniemi JJ, Virtanen HE, Wohlfahrt-Veje C, Löyttyniemi E, Skakkebaek NE, Juul A, et al. . Postnatal changes in testicular position are associated with IGF-I and function of Sertoli and Leydig cells. J Clin Endocrinol Metab. (2018) 103:1429–37. 10.1210/jc.2017-01889
    1. Hadziselimovic F, Zitvkovic D, Bica DTG, Emmons LR. The importance of mini-puberty for fertility in Cryptorchidism. J Urol. (2005) 174:1536–9. 10.1097/01.ju.0000181506.97839.b0
    1. Hadziselimovic F, Emmons LR, Buser MW. A diminished postnatal surge of Ad spermatogonia in cryptorchid infants is additional evidence for hypogonadotropic hypogonadism. Swiss Med Wkly. (2004) 134:381–4.
    1. Hadziselimovic F, Gegenschatz-Schmid K, Verkauskas G, Demougin P, Bilius V, Dasevicius D, et al. . Gene expression changes underlying idiopathic central hypogonadism in cryptorchidism with defective mini-puberty. Sex Dev. (2016) 10:136–46. 10.1159/000447762
    1. Main KM, Schmidt IM, Skakkebæk NE. A possible role for reproductive hormones in newborn boys: Progressive hypogonadism without the postnatal testosterone peak. J Clin Endocrinol Metab. (2000) 85:4905–7. 10.1210/jcem.85.12.7058
    1. Main KM, Schmidt IM, Toppari J, Skakkebæk NE. Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH. Eur J Endocrinol. (2002) 146:75–9. 10.1530/eje.0.1460075
    1. Bougnères P, François M, Pantalone L, Rodrigue D, Bouvattier C, Demesteere E, et al. . Effects of an Early Postnatal Treatment of Hypogonadotropic Hypogonadism with a Continuous Subcutaneous Infusion of Recombinant Follicle-Stimulating Hormone and Luteinizing Hormone. J Clin Endocrinol Metab. (2008) 93:2202–5. 10.1210/jc.2008-0121
    1. Stoupa A, Samara-Boustani D, Flechtner I, Pinto G, Jourdon I, González-Briceño L, et al. . Efficacy and safety of continuous subcutaneous infusion of recombinant human gonadotropins for congenital micropenis during early infancy. Horm Res Paediatr. (2017) 87:103–10. 10.1159/000454861
    1. Gegenschatz-Schmid K, Verkauskas G, Demougin P, Bilius V, Dasevicius D, Stadler MB, et al. . Curative GnRHa treatment has an unexpected repressive effect on Sertoli cell specific genes. Basic Clin Androl. (2018) 28:2. 10.1186/s12610-018-0067-1
    1. Heinrichs C, Bourdoux P, Saussez C, Vis HL, Bourguignon JP. Blood spot follicle-stimulating hormone during early postnatal life in normal girls and Turner's syndrome. J Clin Endocrinol Metab. (1994) 78:978–81.
    1. Fechner PY, Davenport ML, Qualy RL, Ross JL, Gunther DF, et al. Toddler Turner Study Group. Differences in follicle-stimulating hormone secretion between 45,X monosomy Turner syndrome and 45,X/46,XX mosaicism are evident at an early age. J Clin Endocrinol Metab. (2006) 91:4896–902. 10.1210/jc.2006-1157
    1. Chrysis D, Spiliotis BE, Stene M, Cacciari E, Davenport ML. Gonadotropin secretion in girls with Turner syndrome measured by an ultrasensitive immunochemiluminometric assay. Horm Res. (2006) 65:261–6. 10.1159/000092516
    1. Lahlou N, Fennoy I, Carel J-C, Roger M. Inhibin B and anti-müllerian hormone, but not testosterone levels, are normal in infants with nonmosaic Klinefelter syndrome. J Clin Endocrinol Metab. (2004) 89:1864–8. 10.1210/jc.2003-031624
    1. Ross JL, Samango-Sprouse C, Lahlou N, Kowal K, Elder FF, Zinn A. Early androgen deficiency in infants and young boys with 47,XXY Klinefelter syndrome. Horm Res. (2005) 64:39–45. 10.1159/000087313
    1. Aksglaede L, Petersen JH, Main KM, Skakkebæk NE, Juul A. High normal testosterone levels in infants with non-mosaic Klinefelter's syndrome. Eur J Endocrinol. (2007) 157:345–50. 10.1530/EJE-07-0310
    1. Cabrol S, Ross JL, Fennoy I, Bouvattier C, Roger M, Lahlou N. Assessment of leydig and sertoli cell functions in infants with nonmosaic klinefelter syndrome: Insulin-like peptide 3 levels are normal and positively correlated with lh levels. J Clin Endocrinol Metab. (2011) 96:746–53. 10.1210/jc.2010-2103
    1. Bouvattier C, Carel J-C, Lecointre C, David A, Sultan C, Bertrand AM, et al. . Postnatal changes of T, LH, and FSH in 46,XY infants with mutations in the AR gene. J Clin Endocrinol Metab. (2002) 87:29–32. 10.1210/jcem.87.1.7923

Source: PubMed

3
Prenumerera