AMH is secreted by immature Sertoli cells (SC) and is responsible for the regression of Müllerian ducts in the male fetus as part of the sexual differentiation process. AMH is also involved in testicular development and function. AMHs are at their lowest levels in the first days after birth but increase after the first week, likely reflecting active SC proliferation. AMH rises rapidly in concentration in boys during the first month, reaching a peak level at about 6 months of age, and then slowly declines during childhood, falling to low levels in puberty. Basal and FSH-stimulated levels of AMH, might become a useful predictive marker of the spermatogenic response to gonadotropic treatment in young patients with hypogonadotropic hypogonadism. After puberty, AMH is released preferentially by the apical pole of the SC towards the lumen of the seminiferous tubules, resulting in higher concentrations in the seminal plasma than in the serum. Defects in AMH production and insensitivity to AMH due to receptor defects result in the persistent Müllerian duct syndrome. A measurable value of AMH in a boy with bilateral cryptorchidism is predictive of undescended testes, while an undetectable value is highly suggestive of anorchia or ovaries, as would be the case in girls with female pseudohermaphroditism and pure gonadal dysgenesis. Lower serum AMH concentrations in otherwise healthy boys with cryptorchidism, who were compared with their age-matched counterparts with palpable testes, have been reported previously. AMH levels are higher in prepubertal patients with varicocele than in controls. This altered serum profile of AMH in boys with varicoceles may indicate an early abnormality in the regulation of the seminiferous epithelial function. Serum AMH is known to be valuable in assessing gonadal function. As compared to testing involving the administration of human chorionic gonadotropin, the measurement of AMH is more sensitive and equally specific. Measurement of AMH is very useful in young children, because serum gonadotropin concentrations in those who are agonadal are nondiagnostic in midchildhood and serum testosterone concentrations may fail to increase with provocative testing in children with abdominal testes.
Anti-Müllerian hormone (AMH), also named Müllerian inhibiting substance (MIS), is a tissue-specific TGF-beta superfamily growth factor. AMH is secreted by immature Sertoli cells (SC) and is responsible for the regression of Müllerian ducts in the male fetus as part of the sexual differentiation process [
In the 7th week of gestation, the undifferentiated gonads differentiate into a testis in the XY embryo. Gonadal cells become segregated in two compartments: testicular cords and interstitial tissue. Testicular cords are composed by somatic SC and germ cells, surrounded by a basal membrane and peritubular cells. SC produce AMH and inhibin B. In early fetal life AMH expression is triggered by SOX9 gene, and enhanced by SF1 and WT1, independently of gonadotropic control [
Müllerian ducts regress in the male fetus during the 8th and 9th week of gestation through apoptosis and epithelial-mesenchymal transformation occurring in a cranial-to-caudal direction. By week 10, Müllerian ducts become insensitive to AMH [
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 the 7th day of live, gonadotropins level is high again. Leydig’s cell testosterone (T) production follows the LH surge, with a certain delay. Testosterone level is high during whole neonatal life. SC-specific peptides inhibin B and AMH are at their lowest levels in the first days after birth but increase after the first week, likely reflecting active SC proliferation [
In humans, androgens both induce spermatogenesis and repress AMH. Androgen receptor (AR) protein is present in Leydig and peritubular cells of fetal and neonatal human testis, but not in SC. The absence of AR expression in SC of fetal and neonatal human testis contributes to the lack of germ cell maturation and of AMH repression despite strong testicular testosterone biosynthesis.
AMH is undetectable (54%) or very low (95% CI: <2–16 pmol/L) in female infants.
The pubertal decline in AMH results from gradual activation of the hypothalamic-pituitary-gonadal axis, and subsequent increase in intratesticular testosterone, rather than from the interaction between SC and spermatogenic cells [
The close relationship between AMH and inhibin B suggests that inhibin B is an indirect indicator of AR-mediated SC maturation [
While AMH expression is downregulated by meiotic germ cells, the expression of inhibin B
AMH expression and secretion by SC is regulated by inhibitory paracrine actions of intratesticular testosterone and neighbouring germ cells and by a stimulating hormonal effect of FSH. The effect of FSH on testicular AMH production might be due to a direct effect on AMH expression in each individual SC, a proliferative effect on SC, or both. The prepubertal testis is mainly composed of SC, which represent more than 75% of gonadal mass [
In the human adult testis, spermatogenesis is under control of FSH and LH. FSH acts directly on SC, LH induces testosterone production after Leydig cell stimulation. Intratesticular testosterone acts via a paracrine mechanism on AR expressed by target cells situated in the seminiferous tubules [
AMH in the testis is secreted by SC both apically into seminiferous tubules and basally towards the interstitium and circulation. After puberty, AMH is released preferentially by the apical pole of the SC towards the lumen of the seminiferous tubules, resulting in higher concentrations in the seminal plasma than in the serum [
Ambiguous genitalia due to impaired androgen secretion or action may be a result of various conditions with low, normal, or high AMH level. Defects in AMH production and insensitivity to AMH due to receptor defects result in the persistent Müllerian duct syndrome (PMDS) [
In the newborn, defects of androgen signaling in target organs result in an anatomical phenotype of Leydig cell-specific hypogonadism causing androgen deficiency. In the complete form of androgen insensitivity syndrome, female external genitalia with short vagina and the absence of uterus and Fallopian tubes reflect the lack of androgen action together with the normal AMH production [
AMH signals through two membrane receptors: the type 2 receptor (AMHR2), which binds to AMH, and a type 1 receptor involved in signal transduction [
Congenital HH affects the development of SC [
A measurable value of AMH in a boy with bilateral cryptorchidism is predictive of undescended testes, while an undetectable value is highly suggestive of anorchia or ovaries, as would be the case in girls with female pseudohermaphroditism and pure gonadal dysgenesis [
The first phase of typical testicular descent takes place between the 10th and 15th week of human gestation [
Unilateral cryptorchidism carries an increased risk of infertility in adulthood. Up to 30% of men operated on in childhood for unilateral cryptorchidism are likely to be subfertile in later life [
Lower serum AMH concentrations in otherwise healthy boys with cryptorchidism, who were compared with their age-matched counterparts with palpable testes, have been reported in several studies [
In a large study of 124 boys with varicocele Trigo et al. showed that AMH levels were higher in prepubertal patients with varicocele than in controls. Similarly, inhibin B levels were higher in pubertal boys with varicoceles than in the controls [
In another study, Goulis et al. measured peripheral vein and spermatic vein inhibin B and AMH concentrations. In peripheral vein inhibin B, concentrations in men with varicocele were lower as compared to controls, but there was no difference in AMH concentrations. Spermatic vein inhibin B concentrations in men with varicocele were higher compared to those of peripheral vein. On the contrary, spermatic vein AMH concentrations were lower compared to those from peripheral vein [
Serum AMH is known to be valuable in assessing gonadal function [
AMH is one of the key factors conditioning the normal development of male genitals. Serum AMH determination is clinically valuable in assessing gonadal function. Basal and FSH-stimulated levels of AMH, might become a useful predictive marker of the spermatogenic response to gonadotropic treatment in young patients with hypogonadotropic hypogonadism. A measurable value of AMH in a boy with bilateral cryptorchidism is predictive of undescended testes, while an undetectable value is highly suggestive of anorchia or ovaries, as would be the case in girls with female pseudohermaphroditism and pure gonadal dysgenesis. AMH levels are higher in prepubertal patients with varicocele than in controls, which indicate an early abnormality in the regulation of the seminiferous epithelial function.