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      Activation of the Hypothalamic-Pituitary-Gonadal Axis in Infancy: Minipuberty

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          Abstract

          The hypothalamic-pituitary-gonadal (HPG) axis is active in the midgestational foetus but silenced towards term because of the negative feedback effects mediated by the placental hormones. This restraint is removed at birth, leading to reactivation of the axis and an increase in gonadotrophin levels. Gonadotrophin levels are high during the first 3 months of life but decrease towards the age of 6 months except for FSH levels in girls that remain elevated until 3-4 years of age. After this, the HPG axis remains quiescent until puberty. The postnatal gonadotrophin surge results in gonadal activation in both sexes. In boys, testosterone levels rise to a peak at 1-3 months of age and then decline following LH levels. Postnatal HPG axis activation is associated with penile and testicular growth and therefore considered important for the development of male genitalia. In girls, elevated gonadotrophin levels result in the maturation of ovarian follicles and in an increase in oestradiol levels. Biological significance and possible long-term consequences of this minipuberty remain elusive, as do the mechanisms that silence the HPG axis until puberty. However, the first months of life provide a ‘window of opportunity' for functional studies of the HPG axis prior to pubertal development.

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          Changes in anti-Müllerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years.

          L Aksglaede, K. Sørensen, M. Boas … (2010)
          Anti-Müllerian hormone (AMH), which is secreted by immature Sertoli cells, triggers the involution of the fetal Müllerian ducts. AMH is a testis-specific marker used for diagnosis in infants with ambiguous genitalia or bilateral cryptorchidism. The aim of the study was to describe the ontogeny of AMH secretion through life in healthy males. This was a population-based study of healthy volunteers. PARTICIPANTS included 1027 healthy males from birth (cord blood) to 69 yr. A subgroup was followed up longitudinally through the infantile minipuberty [(in cord blood, and at 3 and 12 months), n=55] and another group through puberty [(biannual measurements), n=83]. Serum AMH was determined by a sensitive immunoassay. Serum testosterone, LH, and FSH were measured, and pubertal staging was performed in boys aged 6 to 20 yr (n=616). Serum AMH was above the detection limit in all samples with a marked variation according to age and pubertal status. The median AMH level in cord blood was 148 pmol/liter and increased significantly to the highest observed levels at 3 months (P<0.0001). AMH declined at 12 months (P<0.0001) and remained at a relatively stable level throughout childhood until puberty, when AMH declined progressively with adults exhibiting 3-4% of infant levels. Based on this extensive data set, we found detectable AMH serum levels at all ages, with the highest measured levels during infancy. At the time of puberty, AMH concentrations declined and remained relatively stable throughout adulthood. The potential physiological role of AMH and clinical applicability of AMH measurements remain to be determined.
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            Time course of the serum gonadotropin surge, inhibins, and anti-Müllerian hormone in normal newborn males during the first month of life.

            Ignacio Bergadá, Patricia Bedecarrás, Stella M. Campo … (2006)
            Newborns with ambiguous genitalia or males with nonpalpable gonads usually require an early assessment of the presence and functional state of testicular tissue. 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. We conducted a cross-sectional and longitudinal study. 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). Serum levels of gonadotropins, testosterone, AMH, and inhibins were measured. 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-alphaC) 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). Sertoli cell markers AMH and inhibin B are the earliest useful markers indicating the existence of normal testicular tissue.
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              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.

              Claus Gravholt, Anna-Maria Andersson, Katharina Main … (2010)
              In adult women, anti-Müllerian hormone (AMH) is related to the ovarian follicle pool. Little is known about AMH in girls. The objective of the study was to provide a reference range for AMH in girls and adolescents and to evaluate AMH as a marker of ovarian function. The study was conducted at a tertiary referral center for pediatric endocrinology. We measured AMH in 926 healthy females (longitudinal values during infancy) as well as in 172 Turner syndrome (TS) patients according to age, karyotype (A: 45,X; B: miscellaneous karyotypes; C: 45,X/46,XX), and ovarian function (1: absent puberty; 2: cessation of ovarian function; 3: ongoing ovarian function). AMH was undetectable in 54% (38 of 71) of cord blood samples (<2; <2-15 pmol/liter) (median; 2.5th to 97.5th percentile) and increased in all (37 of 37) infants from birth to 3 months (15; 4.5-29.5 pmol/liter). From 8 to 25 yr, AMH levels were stable (19.9; 4.7-60.1 pmol/liter), with the lower level of the reference range clearly above the detection limit. AMH levels were associated with TS-karyotype groups (median A vs. B: <2 vs. 3 pmol/liter, P = 0.044; B vs. C: 3 vs. 16 pmol/liter, P < 0.001) as well as with ovarian function (absent puberty vs. cessation of ovarian function: <2 vs. 6 pmol/liter, P = 0.004; cessation of ovarian function vs. ongoing ovarian function: 6 vs. 14 pmol/liter, P = 0.001). As a screening test of premature ovarian failure in TS, the sensitivity and specificity of AMH less than 8 pmol/liter was 96 and 86%, respectively. AMH seems to be a promising marker of ovarian function in healthy girls and TS patients.
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                Author and article information

                Journal
                Journal ID (publisher-id): HRP
                Journal ID (nlm-ta): Horm Res Paediatr
                Journal ID (doi): 10.1159/issn.1663-2818
                Title: Hormone Research in Paediatrics
                Publisher: S. Karger AG
                ISSN (Print): 1663-2818
                ISSN (Electronic): 1663-2826
                Publication date Subscription-year: 2014
                Publication date (Print): August 2014
                Publication date (Electronic): 05 July 2014
                Volume: 82
                Issue: 2
                Pages: 73-80
                Affiliations
                aDepartment of Pediatrics, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland; bWilliam Harvey Research Institute, Barts and the London Queen Mary University of London, London, UK
                Author notes
                *Prof. Leo Dunkel, William Harvey Research Institute Barts and the London Queen Mary University of London, London EC1M 6BQ (UK), E-Mail l.dunkel@qmul.ac.uk
                Article
                Publisher ID: 362414 Other ID: Horm Res Paediatr 2014;82:73-80
                DOI: 10.1159/000362414
                PubMed ID: 25012863
                SO-VID: 2eb31a4b-1d74-4a7e-a432-61632bd3efe9
                Copyright © © 2014 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 22 January 2014
                Date accepted : 21 March 2014
                Page count
                Figures: 3, Pages: 8
                Categories
                Subject: Mini Review

                ScienceOpen disciplines: Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Keywords: Sex steroid,Infancy,Hypothalamic-pituitary-gonadal axis,Minipuberty,Postnatal gonadotrophin surge
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes, Neurology, Nutrition & Dietetics, Sexual medicine, Internal medicine, Pharmacology & Pharmaceutical medicine
                Keywords: Sex steroid, Infancy, Hypothalamic-pituitary-gonadal axis, Minipuberty, Postnatal gonadotrophin surge

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