To the Editor:
We read with interest the recent article by Hero et al. (1) showing that antimüllerian hormone (AMH) is one of the earliest signs of pubertal development in healthy boys, occurring before any notable increase in testis volume or serum testosterone. Owing to its longitudinal design, this study provides conclusive evidence for similar observations made in previous cross-sectional studies, indicating that the early increase in intratesticular testosterone is responsible for the inhibition of AMH expression (2-4). The authors conclude from their results that Sertoli cells must begin to express the androgen receptor before the clinical onset of puberty. This does not contradict what was reported by Boukari et al. (5), who did not report the existence of androgen receptor in peri-pubertal boys because their study only included fetal, newborn, and adult testis samples. Interestingly, a recent study of our group (6) described that androgen receptor expression is first observed in the nuclei of few Sertoli cells at the age of 5 months. Weak labeling can be seen in 2–15% of Sertoli cells until 4 years of age and progressively increases to high levels of androgen receptor expression in more than 90% of Sertoli cell nuclei by the age of 8 years (Figure 1). Thereafter, an intense signal is present in almost all Sertoli cells. The presence of androgen receptor in boys older than 8 years explains the early pubertal decline of AMH induced by intra-testicular testosterone rise.
Romina Grinspon, M.D., Ph.D.
Héctor Chemes, M.D., Ph.D.
Rodolfo A. Rey, M.D., Ph.D.
Centro de Investigaciones Endocrinológicas (CEDIE), División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina
1. Hero M, Tommiska J, Vaaralahti K, et al. Circulating antimüllerian hormone levels in boys decline during early puberty and correlate with inhibin B. Fertil Steril 2012; 97:1242-7.
2. Rey R, Lordereau-Richard I, Carel JC, et al. Anti-müllerian hormone and testosterone serum levels are inversely related during normal and precocious pubertal development. J Clin Endocrinol Metab 1993; 77:1220-6.
3. Aksglæde L, Sorensen K, Boas M, 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.
4. Grinspon RP, Bedecarrás P, Ballerini MG, et al. Early onset of primary hypogonadism revealed by serum anti-Mullerian hormone determination during infancy and childhood in trisomy 21. Int J Androl 2011; 34:e487-e98.
5. Boukari K, Meduri G, Brailly-Tabard S, et al. Lack of androgen receptor expression in Sertoli cells accounts for the absence of anti-Müllerian hormone repression during early human testis development. J Clin Endocrinol Metab 2009; 94:1818-25.
6. Chemes HE, Rey RA, Nistal M, et al. Physiologic 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.
Figure 1 (click for larger view). Percentage of Sertoli cells with positive immunostaining for the androgen receptor in human fetal and postnatal testes. Reproduced with permission from ref. 6. Copyright The Endocrine Society 2008.
The authors declined to respond to this letter.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2012.06.003