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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2006-1079
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The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 10 4092-4098
Copyright © 2006 by The Endocrine Society

Time Course of the Serum Gonadotropin Surge, Inhibins, and Anti-Müllerian Hormone in Normal Newborn Males during the First Month of Life

Ignacio Bergadá1, Carlos Milani1, Patricia Bedecarrás, Luz Andreone, M. Gabriela Ropelato, Silvia Gottlieb, César Bergadá2, Stella Campo and Rodolfo A. Rey

Centro de Investigaciones Endocrinológicas and División de Endocrinología (I.B., C.M., P.B., L.A., M.G.R., S.G., C.B., S.C., R.A.R.), Hospital de Niños R. Gutiérrez, C1425EFD Buenos Aires, Argentina; Instituto de Análisis Clínicos (C.M.), B6000FID Junin, Argentina; and Departamento de Histología, Biología Celular, Embriología y Genética (R.A.R.), Facultad de Medicina, Universidad de Buenos Aires, C1121ABG Buenos Aires, Argentina

Address all correspondence and requests for reprints to: Prof. Rodolfo Rey, M.D., Ph.D., CEDIE, Hospital de Niños R. Gutiérrez, Gallo 1330, C1425EFD Buenos Aires, Argentina. E-mail: rodolforey{at}cedie.org.ar.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: Newborns with ambiguous genitalia or males with nonpalpable gonads usually require an early assessment of the presence and functional state of testicular tissue.

Objective: Our objective was to characterize the precise ontogeny of the serum patterns of gonadotropins, testosterone, anti-Müllerian hormone (AMH), and inhibins in normal newborn boys.

Design: We conducted a cross-sectional and longitudinal study.

Subjects: Serum samples were obtained in 57 boys and 13 girls on d 2 of life. A second sample was obtained on d 7, 10, 15, 20, and 30 (boys) and on d 30 (girls).

Main Outcome Measures: Serum levels of gonadotropins, testosterone, AMH, and inhibins were measured.

Results: In males, LH and FSH were undetectable or very low on d 2. By d 7, LH increased to 3.94 ± 3.19 IU/liter (mean ± SD) and FSH to 2.04 ± 1.67 IU/liter. LH/FSH ratios were 0.40 ± 0.11 (d 2) and 2.02 ± 0.20 (d 30). AMH rose from 371 ± 168 pmol/liter (d 2) to 699 ± 245 pmol/liter (d 30), and inhibin B rose from 214 ± 86 ng/liter (d 2) to 361 ± 93 ng/liter (d 30). The inhibin {alpha}-subunit precursor (pro-{alpha}C) remained stable during the first month of life. Testosterone levels were 66 ± 42 ng/dl (d 2), 82 ± 24 ng/dl (d 20), and 210 ± 130 ng/dl (d 30). A sexual dimorphism was observed in AMH and inhibin B (lower in girls on d 2 and 30), in LH/FSH ratio (lower in girls on d 30) and in testosterone (lower in girls on d 30).

Conclusions: Sertoli cell markers AMH and inhibin B are the earliest useful markers indicating the existence of normal testicular tissue.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
THE HYPOTHALAMIC-PITUITARY-GONADAL axis function shows a marked sexual dimorphism from fetal life in the pituitary content and secretion of LH and FSH (1, 2, 3); a clear preponderance of FSH is observed in females when compared with males, which persists up to puberty (4, 5, 6, 7, 8). After birth, the gonadotropic surge occurs as a consequence of the abrupt decrement of sexual steroids mainly from placental origin (2, 9, 10). This early differential pattern of gonadotropin secretion appears to be at least in part influenced by the hypothalamic androgen imprinting as shown in models of complete androgen insensitivity (11).

In newborns with ambiguous genitalia or males with nonpalpable gonads, diagnosis and management must be accurately and promptly undertaken. One important aspect of this diagnostic evaluation is the need of an early assessment of gonadal function (12, 13). For many years, the evaluation of testicular function has relied on serum testosterone determination, which reflects exclusively Leydig cell activity. Fragmentary data from different studies indicate that serum testosterone levels are higher in boys than in girls during the first hours after birth (9) but decrease dramatically in the first week of life (14, 15) to increase again after the second week (16). Sertoli cell function has usually been assessed indirectly by measuring FSH levels. Normal FSH levels in early infancy have been extensively studied in the past (1, 2, 4, 9), but no detailed survey of possible changes in the evolutionary pattern of serum FSH in neonates has been performed using ultrasensitive assays. On the other hand, assessment of Sertoli cell function using specific markers, e.g. inhibin B and anti-Müllerian hormone (AMH), has become available in the last few years. Few studies have explored the levels of inhibin B (17, 18, 19) or AMH (20, 21, 22) in groups of children that included neonates, but age ranges were relatively wide. In patients with nonpalpable gonads or ambiguous genitalia, hormonal data are frequently obtained during the first days or weeks after birth. However, the lack of precise data on the ontogeny of normal circulating levels of gonadotropins, testosterone, and gonadal peptides may represent a major obstacle for the diagnostic process of a condition that needs a prompt resolution to minimize anxiety in the newborn’s family.

The aim of the present study was to determine the serum patterns of gonadotropins, testosterone, AMH, inhibin B, and inhibin {alpha}-subunit precursor (pro-{alpha}C) in normal newborn boys, systematically classified in homogeneous age groups, to characterize the precise ontogeny of the male hypothalamic-pituitary-gonadal axis function during the first month of life. For comparison, we also studied the female hypothalamic-pituitary-gonadal axis at birth and at the end of the first month of life.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Fifty-seven boys and 13 girls born at term and appropriate for gestational age at the Hospital de Agudos and the Clínica Sanatorio Junín (Junín, Argentina) between March and May 2002, and participating in a regional pediatric health program including screening for the detection of inborn errors of metabolism, were included in the study. The study was approved by the local institutional review boards, and only those newborns whose parents gave written informed consent were included. An aliquot of the blood sample routinely obtained in all individuals during the second day of life (between the 36th and 48th hour after birth) was used for this study. A second sample was obtained in 10 boys between d 6 and 8 after birth (group A), 13 boys between d 10 and 12 (group B), 12 boys between d 13 and 16 (group C), 11 boys between d 18 and 22 (group D), and 11 boys between d 30 and 35 (group E). Age groups were identified according to the age of the largest number of individuals in the group. In the 13 girls, a second sample was obtained between d 30 and 33. Serum was obtained by centrifugation and stored at –20 C until assayed.

Hormone assays

Serum FSH and LH were measured by time-resolved immunofluorometric assays (DELFIA; Wallac, Inc., Turku, Finland), as previously published (8). The detection limits of the assays were 0.10 and 0.05 IU/liter, respectively. World Health Organization International Reference Preparation 68/40 and the Second International Reference Preparation of Pituitary 78/549 were used as LH and FSH standards, respectively. Intra- and interassay coefficients of variation were as follows: for FSH, less than 1.8 and 7.6% for a dose range of 3.8–26.8 IU/liter, respectively, and for LH, less than 2.2 and 9.5% for a dose range 3.8–39.4 IU/liter, respectively.

Serum testosterone was measured by RIA using a commercial kit (Diagnostic System Laboratories, Webster, TX) with a detection limit of 10 ng/dl; the intra- and interassay coefficients of variation were less than 12%. Each sample was separated into two aliquots, one of which was subjected to ethyl ether extraction (23).

Serum AMH was measured using the AMH/Müllerian-inhibiting substance ELISA kit (Immunotech-Beckman, Marseilles, France). A preparation of recombinant human AMH was used to construct a standard curve. The detection limit of the assay was 0.7 pmol/liter (0.1 ng/ml); intra- and interassay coefficients of variation were 5.3 and 8.7%, respectively, for a serum AMH concentration of 35 pmol/liter and 4.9 and 7.8% for a serum AMH concentration of 1100 pmol/liter. No cross-reaction was observed with TGF-ß (21).

Serum inhibin B and pro-{alpha}C were measured using two-site ELISAs (Oxford Bio-Innovation Ltd., Oxon, UK) specific for each peptide as previously described (24). Recombinant inhibin B (Genentech, San Francisco, CA) and a partially purified (>75% purity) pro-{alpha}C preparation were used as standards. The assay sensitivity was 15 pg/ml for inhibin B and 2 pg/ml for pro-{alpha}C. Intra- and interassay coefficients of variation were less than 10% for all assays.

Statistical analyses

A normality test, one-sample t test, one-way ANOVA with Bartlett’s posttest, paired t test, unpaired t test with Welch’s correction, and/or Tukey-Kramer multiple comparison test were performed as required, using GraphPad Prism version 4.00 for Windows (GraphPad Software, San Diego, CA; www.graphpad.com).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The time course of serum levels of LH, FSH, AMH, inhibin B, pro-{alpha}C, and testosterone during the first month of life in boys is shown in Fig. 1Go. Both gonadotropins were low in the second day of life but increased significantly in the first week (Fig. 1Go, A and B, and Table 1Go). On d 2, serum levels of LH and FSH did not show a normal distribution (normality tests for LH, Kolmogorov-Smirnov distance = 0.223, P = 0.011; for FSH, Kolmogorov-Smirnov distance = 0.203, P = 0.027); 18 of 57 FSH samples and 18 of 57 LH samples were below the detection limit of the assays (<0.05 IU/liter for both). In 10 of 18 cases, both gonadotropins were undetectable in the same individual. Median serum LH was 0.12 IU/liter (interquartile range, 0–0.29), and median FSH was 0.17 IU/liter (interquartile range, 0–0.36 IU/liter). From d 7 onward, values of both gonadotropins showed a normal distribution in all samples analyzed (normality tests, P > 0.05). By d 7, both LH and FSH increased significantly. Thereafter, there were no significant changes in serum levels of both gonadotropins. It is noteworthy that FSH was higher than LH on d 2, resulting in a mean individual LH/FSH ratio of 0.40 ± 0.11 (mean ± SEM; Fig. 2Go). However, the subsequent increase was more pronounced in LH, and the mean individual LH/FSH ratio increased to 1.87 ± 0.21 by d 7. Thereafter, the LH/FSH ratio remained significantly higher than 1.


Figure 1
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  		FIG. 1. Serum levels of pituitary-testicular axis hormones in boys during the first month of life. Two serum samples were obtained in 57 normal boys, the first in their second day of life and a second sample between d 7 and 35.

 

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  		TABLE 1. Serum levels of gonadotropins and gonadal hormones in normal newborns

 

Figure 2
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  		FIG. 2. LH/FSH ratio in normal newborns. LH and FSH were measured in the same individuals. Results are shown as mean ± SEM of individual ratios in 10–13 newborns in each group, except for d 2 (D2) boys, where 57 individuals were included. Data were analyzed using a one-way ANOVA and a Tukey’s multiple comparison posttest. Different letters indicate significant differences (P < 0.05) between groups. An asterisk indicates that the LH/FSH ratio is significantly different from 1 (P < 0.05) using a one-sample t test.

 
Serum levels of all testicular hormones determined showed a normal distribution throughout the first month of life (normality tests, P > 0.05). Like gonadotropins, testosterone, AMH, and inhibin B were at their lowest levels on d 2 and increased in the following weeks (Fig. 1Go and Table 1Go). When measured twice in the same individuals, testosterone levels remained stable until d 10 in extracted samples (Fig. 1CGo and Table 1Go). Thereafter, a trend to increase was observed. Although a statistically significant increment could not be demonstrated in all age groups, probably owing to the relatively small sample size, testosterone levels were higher on d 14 compared with d 2 in 10 of 12 cases. The mean increment between d 2 and 14 was 40 ± 20 ng/dl (mean ± SEM). Also on d 20, testosterone was higher compared with d 2 in eight of 10 cases. The mean increment was 20 ± 13 ng/dl. By d 30, the rise in serum testosterone was evident. The mean increment was 210 ± 46 ng/dl. AMH levels were not different between d 2 and 7, but a significant increase was already observed between d 2 and 10. AMH was also higher on d 14, 20, and 30 than on d 2 (Fig. 1DGo and Table 1Go). Serum inhibin B increased significantly from d 2 to d 7, but no additional elevation was observed thereafter (Fig. 1FGo and Table 1Go). Levels of pro-{alpha}C were high in the second day of life, decreased slightly until d 7, remained stable until d 20, and further decreased on d 30 (Fig. 1EGo and Table 1Go). These slight changes were not statistically significant.

In newborn girls, serum levels of gonadotropins were also very low on d 2 (both LH and FSH levels were undetectable in eight of 13 girls) but increased significantly during the first month (Fig. 3Go, A and B). FSH was higher than LH on d 2, which resulted in a LH/FSH ratio similar to that observed in boys (mean ± SEM, 0.59 ± 0.08). However, unlike in boys, the increase in FSH was more substantial than that of LH, and the LH/FSH ratio was 0.06 ± 0.01 on d 30 (Fig. 2Go). Interestingly, serum LH was lower in girls than in boys on d 2 and at the end of the first month of life (Table 1Go). FSH was also lower in girls than in boys on d 2, but it was considerably higher in girls on d 30 (Table 1Go).


Figure 3
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  		FIG. 3. Evolution of pituitary-testicular hormones in normal female neonates. Paired comparison of hormone serum levels in the same individuals in groups of 13 girls. The horizontal lines represent the mean. Statistical analysis was performed using a two-tailed paired t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001; NS, not significant. D, Day.

 
In extracted serum samples, testosterone levels were moderately, but significantly, lower in girls than in boys on d 2 (Table 1Go). Because no significant increase was observed in serum testosterone in girls during the first month (Fig. 3CGo), by d 30 the difference between sexes was even more pronounced (Table 1Go). Despite the significant differences observed between group means both at 2 and 30 d of life, it should be remarked that serum testosterone ranges overlapped slightly on d 2 (girls, 14–42 ng/dl; boys, 18–212 ng/dl) but not on d 30 (girls, 25–48 ng/dl; boys, 98–508 ng/dl). Testosterone was also measured in samples without previous extraction; compared with extracted samples, in boys, values were 3.28-fold at 2 d, 2.13-fold at 7 d, 2.16-fold at 10 d, 1.32-fold at 14 d, 1.54-fold at 20 d, and 0.70-fold at 30 d; in girls, values were 4.63-fold at 2 d and 1.33-fold at 30 d.

Serum AMH was very low in girls throughout the first 30 d of life (Fig. 3DGo), with no overlap with the male span. Female values ranged from undetectable to 25 pmol/liter on d 2 and to 64 pmol/liter on d 30, whereas male ranges were 114–856 pmol/liter on d 2 and 438-1197 pmol/liter on d 30. Inhibin B was undetectable in all d-2 female samples and increased considerably by d 30 (Fig. 3FGo). However, it remained significantly lower than in boys (Table 1Go). No overlap was observed between sexes: on d 2, inhibin B was undetectable in females, whereas the male range was 57–465 ng/liter; on d 30, the female range was 65–215 ng/liter, and the male range was 248–540 ng/liter. Pro-{alpha}C levels were not significantly different between sexes on d 2 or 30.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
This is the first study to report in detail the pattern of variation in serum gonadotropins and testicular markers of both Sertoli and Leydig cell function along the first month of life. Previous studies had explored some of the components of the pituitary-gonadal axis during the first days of life. Corbier et al. (9) reported sex differences in serum gonadotropins in the first few hours after birth. Shinkawa et al. (25) described sex differences in serum gonadotropins in premature and mature newborns. Schmidt and Schwarz (26) also studied serum gonadotropins in neonates. In all these studies, gonadotropin levels were determined by RIA. More recently, Chada et al. (27, 28) reported normal gonadotropin ranges using more sensitive immunochemiluminometric assays. In the present study, we show results obtained with ultrasensitive immunofluorometric assays for the measurement of serum gonadotropins, which are most extensively used in pediatric populations because of their capacity for detecting very low gonadotropin levels. In our study, serum LH, which was low on d 2, had a remarkable increment from d 7 throughout the whole month. Using an ultrasensitive assay, we found serum LH levels on d 2 ranging from undetectable to 1.2 IU/liter. This relatively wide range may be due to some remnant of the known brisk rise of LH that occurs predominantly in males during the first 3–6 h of life with a gradual decrease thereafter (9). A similar pattern was observed for FSH, although the increment was lesser. Interestingly, the LH/FSH ratio was similar in boys and girls on d 2 but sexually dimorphic by the end of the first month, already resembling the pattern described throughout puberty (4, 5, 6, 7).

Circulating inhibin B levels showed a significant increment between birth and d 7 in boys. Several studies have already shown high levels of serum inhibin B in cord blood of males, whereas undetectable levels observed in females highlight the early testicular ability to synthesize dimeric inhibin B (8, 17, 29, 30, 31). However, only few studies have explored the postnatal rise of inhibin B; one work describes the changes in serum inhibin B in the first week of life (17), and four other studies do not discriminate results obtained within the first months of life (28, 30, 32, 33). Our results are in keeping with the latter, showing an increment of inhibin B in early postnatal life; we particularly show that the rise in inhibin B takes place in the first week with no further changes. The production of inhibin B during the first month of life may be linked to the marked proliferation of Sertoli cells that occurs after midgestation with a further increment after birth probably enhanced by the postnatal gonadotropic surge (34, 35). It is noteworthy that inhibin B levels were always clearly above the detection limit of the assay from d 2 and throughout the whole studied period, confirming that it is a useful marker to assess the presence of Sertoli cells indicating the existence of functional testes in newborn boys with nonpalpable gonads.

The high-molecular-weight precursor of inhibin {alpha}-subunit, pro-{alpha}C, is expressed by Sertoli cells and Leydig cells (36). In Sertoli cells, it dimerizes with the ßB subunit to form inhibin B. In this study, we have found a differential pattern of pro-{alpha}C compared with inhibin B. We have previously shown that circulating levels of pro-{alpha}C are similar to those of inhibin B from approximately 3 months after birth until puberty, resulting in a serum inhibin B/pro-{alpha}C ratio of approximately 1. It was surprising to find very high serum levels of pro-{alpha}C already on d 2 of age without any further change through the first month of life. Furthermore, these serum levels are much higher than those observed later in infancy and childhood and similar to those observed in adult men with azoospermia, concomitantly with low inhibin B. Pro-{alpha}C is high in fetal circulation without a differential pattern between sexes (37). Furthermore, in cord blood, pro-{alpha}C levels are 3-fold higher than the levels we report on d 2 of postnatal life (38). Our findings might reflect that most of pro-{alpha}C found at birth is from placental origin; however, the possible adrenal contribution to the high {alpha}-inhibin subunit serum levels observed postnatally cannot be ruled out (39, 40).

As previously reported (20, 22), we have found that AMH levels are low at birth. However, there is a clear sexual dimorphism, which increases during infancy and childhood (20, 21, 22, 41), highlighting the usefulness of serum AMH as a marker of the presence of functional Sertoli cells in patients with nonpalpable gonads (42) or ambiguous genitalia (21, 43). An increment in AMH is seen in the first 10 d of life, with a sustained progression during the whole first month of life, as observed in our work. A peak is reached in the first 6–12 months of age (20, 21, 22). This increment may reflect the active proliferation of Sertoli cells observed in that period (34, 35). Based on previous results (44, 45), we believe that the FSH surge may also contribute to the enhanced testicular secretion of AMH after d 7.

The pattern of circulating testosterone levels has been extensively described in newborns. Corbier et al. (9) studied the first 24 h after birth and showed an increase in testosterone levels in boys at 3–12 h. Forest and colleagues (16, 46) were the first to show that testosterone levels are somewhat lower in the first 15 d. Our results are in line with the aforementioned. In an effort to dissect the pattern of testosterone circulating levels through the first month of life, we compared hormone levels in the same individual at 2 and 7, 10, 14, 20, or 30 d after birth. After finding low levels on d 2, we were able to identify the age of 10 d as a breakpoint where testosterone starts rising again. In agreement with Forest et al. (47), we found that serum testosterone was only moderately higher in boys than in girls in the first days of life, with a significant overlap in circulating levels between sexes; this makes basal testosterone a less useful marker of the presence of testicular tissue before the second to third weeks. Another essential issue to be considered is the absolute need for previous extraction of serum samples to avoid an overestimation of the circulating levels of testosterone observed in females and in males during the first weeks of life, as already shown in different conditions in infants and adults where testosterone is low (48).

In summary, our present results, using highly sensitive assays to assess the circulating levels of specific markers of the different cell populations, add to previous evidence the possibility of drawing a precise picture of the ontogeny of the pituitary-testicular axis endocrine function in the neonatal period. The known transient increase of gonadotropins in the first hours after birth is followed by a sharp decrease as of the second day of life; by d 7, gonadotropins are high again. Leydig cell testosterone production follows the LH surge, with a certain delay. Sertoli cell-specific peptides inhibin B and AMH are at their lowest levels in the first days after birth but increase as of the first week, likely reflecting active Sertoli cell proliferation. A sexual dimorphism is observed in the patterns of secretion of gonadotropins, testosterone, and gonadal peptides. We conclude that the typical male pattern of the circulating Sertoli cell markers observed as of the first days of life taken together with the clearly differential pattern of the LH/FSH ratio by the first week highlights their usefulness as markers of normally regulated testicular tissue throughout the first month of life.


   Acknowledgments
 
We are fully grateful to Dr. María G. Ballerini and Mrs. Silvia Fragole, Rosa Guiñazú, Ana María Montese, and Perla Rossano for their skillful technical assistance. We fully acknowledge the collaboration of the medical staff and nurses of Hospital de Agudos and Clínica Sanatorio Junín (Junín, Argentina) for their collaboration.


   Footnotes
 
I.B. is a research associate member of the Gobierno de la Ciudad de Buenos Aires. P.B., S.G., S.C., and R.A.R. are members of the permanent staff of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET).

This work was partially financed by grants PICT of the Agencia Nacional de Promoción Científica y Técnológica and PIP of CONICET (to S.C. and R.A.R.) and by grants of the Consejo de Investigación en Salud of the Gobierno de la Ciudad de Buenos Aires (to I.B. and M.G.R.).

The authors have nothing to declare.

First Published Online July 18, 2006

1 I.B. and C.M. contributed equally to this work. Back

2 C.B. is deceased. Back

Abbreviations: AMH, Anti-Müllerian hormone; pro-{alpha}C, inhibin {alpha}-subunit precursor.

Received May 18, 2006.

Accepted July 7, 2006.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Winter JS, Faiman C, Hobson WC, Prasad AV, Reyes FI 1975 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 40:545–551[Abstract/Free Full Text]
  2. Kaplan SL, Grumbach MM 1976 The ontogenesis of human foetal hormones. II. Luteinizing hormone (LH) and follicle stimulating hormone (FSH). Acta Endocrinol (Copenh) 81:808–829[Abstract/Free Full Text]
  3. Kaplan SL, Grumbach MM 1978 Pituitary and placental gonadotrophins and sex steroids in the human and sub-human primate fetus. Clin Endocrinol Metab 7:487–511[CrossRef][Medline]
  4. Cacciari E, Cicognani A, Pirazoli P, Dallacasa P, Mazzaracchio MA, Tassoni P, Bernardi F, Salardi S, Zappulla F 1976 GH, ACTH, LH and FSH behaviour in the first seven days of life. Acta Paediatr Scand 65:337–341[Medline]
  5. Neely EK, Hintz RL, Wilson DM, Lee PA, Gautier T, Argente J, Stene M 1995 Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr 127:40–46[CrossRef][Medline]
  6. Demir A, Dunkel L, Stenman UH, Voutilainen R 1995 Age-related course of urinary gonadotropins in children. J Clin Endocrinol Metab 80:1457–1460[Abstract]
  7. Belgorosky A, Chahin S, Chaler E, Maceiras M, Rivarola MA 1996 Serum concentrations of follicle stimulating hormone and luteinizing hormone in normal girls and boys during prepuberty and at early puberty. J Endocrinol Invest 19:88–91[Medline]
  8. Ropelato MG, Escobar ME, Gottlieb S, Bergadá C 1997 Gonadotropin secretion in prepubertal normal and agonadal children evaluated by ultrasensitive time-resolved immunofluorometric assays. Horm Res 48:164–172[Medline]
  9. Corbier P, Dehennin L, Castanier M, Mebazaa A, Edwards DA, Roffi J 1990 Sex differences in serum luteinizing hormone and testosterone in the human neonate during the first few hours after birth. J Clin Endocrinol Metab 71:1344–1348[Abstract/Free Full Text]
  10. Grumbach MM, Kaplan SL 1992 The neuroendocrinology of human puberty. An ontogenic perspective. In: Grumbach MM, Sizonenko PC, Aubert ML, eds. Control of the onset of puberty. 8th ed. Baltimore: Williams and Wilkins; 1–68
  11. Bouvattier C, Carel JC, Lecointre C, David A, Sultan C, Bertrand AM, Morel Y, Chaussain JL 2002 Postnatal changes of T, LH, and FSH in 46,XY infants with mutations in the AR gene. J Clin Endocrinol Metab 87:29–32[Abstract/Free Full Text]
  12. Conte FA, Grumbach MM, Kaplan SL 1975 A diphasic pattern of gonadotropin secretion in patients with the syndrome of gonadal dysgenesis. J Clin Endocrinol Metab 40:670–674[Abstract/Free Full Text]
  13. Ogilvy-Stuart AL, Brain CE 2004 Early assessment of ambiguous genitalia. Arch Dis Child 89:401–407[Free Full Text]
  14. Tapanainen J 1983 Hormonal changes during the perinatal period: serum testosterone, some of its precursors, and FSH and prolactin in preterm and fullterm male infant cord blood and during the first week of life. J Steroid Biochem 18:13–18[CrossRef][Medline]
  15. Tomlinson C, Macintyre H, Dorrian CA, Ahmed SF, Wallace AM 2004 Testosterone measurements in early infancy. Arch Dis Child Fetal Neonatal Ed 89:F558–F559
  16. Forest MG, Cathiard AM 1975 Pattern of plasma testosterone and {Delta}4-androstenedione in normal newborns: evidence for testicular activity at birth. J Clin Endocrinol Metab 41:977–980[Abstract/Free Full Text]
  17. De Schepper J, Verlinde F, Cortvrindt R, Callewaert M, Smitz J 2000 Serum inhibin B in normal term-born male and female neonates during the first week of life. Eur J Pediatr 159:465–469[CrossRef][Medline]
  18. Bergadá I, Rojas G, Ropelato MG, Ayuso S, Bergadá C, Campo S 1999 Sexual dimorphism in circulating monomeric and dimeric inhibins in normal boys and girls from birth to puberty. Clin Endocrinol (Oxf) 51:455–460[CrossRef][Medline]
  19. Andersson A, Skakkebæk NE 2001 Serum inhibin B levels during male childhood and puberty. Mol Cell Endocrinol 180:103–107[CrossRef][Medline]
  20. Lee MM, Donahoe PK, Hasegawa T, Silverman B, Crist GB, Best S, Hasegawa Y, Noto RA, Schoenfeld D, MacLaughlin DT 1996 Mullerian inhibiting substance in humans: normal levels from infancy to adulthood. J Clin Endocrinol Metab 81:571–576[Abstract]
  21. Rey RA, Belville C, Nihoul-Fékété C, Michel-Calemard L, Forest MG, Lahlou N, Jaubert F, Mowszowicz I, David M, Saka N, Bouvattier C, Bertrand AM, Lecointre C, Soskin S, Cabrol S, Crosnier H, Léger J, Lortat-Jacob S, Nicolino M, Rabl W, Toledo SP, Bas F, Gompel A, Czernichow P, Josso N 1999 Evaluation of gonadal function in 107 intersex patients by means of serum antimüllerian hormone measurement. J Clin Endocrinol Metab 84:627–631[Abstract/Free Full Text]
  22. Guibourdenche J, Lucidarme N, Chevenne D, Rigal O, Nicolas M, Luton D, Leger J, Porquet D, Noel M 2003 Anti-Mullerian hormone levels in serum from human foetuses and children: pattern and clinical interest. Mol Cell Endocrinol 211:55–63[CrossRef][Medline]
  23. Forest MG, Sizonenko PC, Cathiard AM, Bertrand J 1974 Hypophyso-gonadal function in humans during the first year of life. 1. Evidence for testicular activity in early infancy. J Clin Invest 53:819–828[Medline]
  24. Trigo RV, Bergadá I, Rey R, Ballerini MG, Bedecarrás P, Bergadá C, Gottlieb S, Campo S 2004 Altered serum profile of inhibin B, pro-{alpha}C and anti-Mullerian hormone in prepubertal and pubertal boys with varicocele. Clin Endocrinol (Oxf) 60:758–764[CrossRef][Medline]
  25. Shinkawa O, Furuhashi N, Fukaya T, Suzuki M, Kono H, Tachibana Y 1983 Changes of serum gonadotropin levels and sex differences in premature and mature infant during neonatal life. J Clin Endocrinol Metab 56:1327–1331[Abstract/Free Full Text]
  26. Schmidt H, Schwarz HP 2000 Serum concentrations of LH and FSH in the healthy newborn. Eur J Endocrinol 143:213–215[Abstract]
  27. Chada M, Prusa R, Bronsky J, Pechova M, Kotaska K, Lisa L 2003 Inhibin B, follicle stimulating hormone, luteinizing hormone, and estradiol and their relationship to the regulation of follicle development in girls during childhood and puberty. Physiol Res 52:341–346[Medline]
  28. Chada M, Prusa R, Bronsky J, Kotaska K, Sidlova K, Pechova M, Lisa L 2003 Inhibin B, follicle stimulating hormone, luteinizing hormone and testosterone during childhood and puberty in males: changes in serum concentrations in relation to age and stage of puberty. Physiol Res 52:45–51[Medline]
  29. Andersson AM, Toppari J, Haavisto AM, Petersen JH, Simell T, Simell O, Skakkebæk NE 1998 Longitudinal reproductive hormone profiles in infants: peak of inhibin B levels in infant boys exceeds levels in adult men. J Clin Endocrinol Metab 83:675–681[Abstract/Free Full Text]
  30. Byrd W, Bennett MJ, Carr BR, Dong Y, Wians F, Rainey W 1998 Regulation of biologically active dimeric inhibin A and B from infancy to adulthood in the male. J Clin Endocrinol Metab 83:2849–2854[Abstract/Free Full Text]
  31. Wallace EM, Riley SC, Crossley JA, Ritoe SC, Horne A, Shade M, Ellis PM, Aitken DA, Groome NP 1997 Dimeric inhibins in amniotic fluid, maternal serum, and fetal serum in human pregnancy. J Clin Endocrinol Metab 82:218–222[Abstract/Free Full Text]
  32. Kubini K, Zachmann M, Albers N, Hiort O, Bettendorf M, Wolfle J, Bidlingmaier F, Klingmuller D 2000 Basal inhibin B and the testosterone response to human chorionic gonadotropin correlate in prepubertal boys. J Clin Endocrinol Metab 85:134–138[Abstract/Free Full Text]
  33. Crofton PM, Evans AEM, Groome NP, Taylor MRH, Holland CV, Kelnar CJH 2002 Inhibin B in boys from birth to adulthood: relationship with age, pubertal stage, FSH and testosterone. Clin Endocrinol (Oxf) 56:215–221[CrossRef][Medline]
  34. Müller J, Skakkebæk NE 1984 Fluctuations in the number of germ cells during the late foetal and early postnatal periods in boys. Acta Endocrinol (Copenh) 105:271–274[Abstract/Free Full Text]
  35. Berensztein EB, Sciara MI, Rivarola MA, Belgorosky A 2002 Apoptosis and proliferation of human testicular somatic and germ cells during prepuberty: high rate of testicular growth in newborns mediated by decreased apoptosis. J Clin Endocrinol Metab 87:5113–5118[Abstract/Free Full Text]
  36. Andersson AM, Müller J, Skakkebæk NE 1998 Different roles of prepubertal and postpubertal germ cells and Sertoli cells in the regulation of serum inhibin B levels. J Clin Endocrinol Metab 83:4451–4458[Abstract/Free Full Text]
  37. Riley SC, Wathen NC, Chard T, Groome NP, Wallace EM 1996 Inhibin in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy. Hum Reprod 11:2772–2776[Abstract/Free Full Text]
  38. Riley SC, Leask R, Balfour C, Brennand JE, Groome NP 2000 Production of inhibin forms by the fetal membranes, decidua, placenta and fetus at parturition. Hum Reprod 15:578–583[Abstract/Free Full Text]
  39. Voutilainen R, Erämaa M, Ritvos O 1991 Hormonally regulated inhibin gene expression in human fetal and adult adrenals. J Clin Endocrinol Metab 73:1026–1030[Abstract/Free Full Text]
  40. Spencer SJ, Rabinovici J, Mesiano S, Goldsmith PC, Jaffe RB 1992 Activin and inhibin in the human adrenal gland. Regulation and differential effects in fetal and adult cells. J Clin Invest 90:142–149[Medline]
  41. Long WQ, Ranchin V, Pautier P, Belville C, Denizot P, Cailla H, Lhommé C, Picard JY, Bidart JM, Rey R 2000 Detection of minimal levels of serum anti-Müllerian hormone during follow-up of patients with ovarian granulosa cell tumor by means of a highly sensitive enzyme-linked immunosorbent assay. J Clin Endocrinol Metab 85:540–544[Abstract/Free Full Text]
  42. Lee MM, Donahoe PK, Silverman BL, Hasegawa T, Hasegawa Y, Gustafson ML, Chang YC, MacLaughlin DT 1997 Measurements of serum Müllerian inhibiting substance in the evaluation of children with nonpalpable gonads. N Engl J Med 336:1480–1486[Abstract/Free Full Text]
  43. Stuchi-Perez EG, Lukas-Croisier C, De Castro M, Baptista MT, Ribeiro Scolfaro M, Marques-De-Faria AP, Hackel C, Maciel-Guerra AT, Guerra Júnior G 2000 Evaluation of the tubular and interstitial functions of the testis in 46,XY patients with ambiguous genitalia. J Pediatr Endocrinol Metab 13:605–612[Medline]
  44. Lukas-Croisier C, Lasala C, Nicaud J, Bedecarrás P, Kumar TR, Dutertre M, Matzuk MM, Picard JY, Josso N, Rey R 2003 Follicle-stimulating hormone increases testicular anti-Müllerian hormone (AMH) production through Sertoli cell proliferation and a nonclassical cyclic adenosine 5'-monophosphate-mediated activation of the AMH gene. Mol Endocrinol 17:550–561[Abstract/Free Full Text]
  45. Young J, Chanson P, Salenave S, Noel M, Brailly S, O’Flaherty M, Schaison G, Rey R 2005 Testicular anti-Mullerian hormone (AMH) secretion is stimulated by recombinant human FSH in patients with congenital hypogonadotropic hypogonadism. J Clin Endocrinol Metab 90:724–728[Abstract/Free Full Text]
  46. Forest MG, Cathiard AM, Bertrand JA 1973 Total and unbound testosterone levels in the newborn and in normal and hypogonadal children: use of a sensitive radioimmunoassay for testosterone. J Clin Endocrinol Metab 36:1132–1142[Abstract/Free Full Text]
  47. Forest MG, Cathiard AM, Bertrand JA 1973 Evidence of testicular activity in early infancy. J Clin Endocrinol Metab 37:148–151[Abstract/Free Full Text]
  48. Taieb J, Mathian B, Millot F, Patricot MC, Mathieu E, Queyrel N, Lacroix I, Somma-Delpero C, Boudou P 2003 Testosterone measured by 10 immunoassays and by isotope-dilution gas chromatography-mass spectrometry in sera from 116 men, women, and children. Clin Chem 49:1381–1395[Abstract/Free Full Text]



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