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N Josso

Publications and source records attributed to N Josso.

At least 55 records · Page 3Linked to original sources
PubMed1993

Radiological findings in three cases of persistent müllerian duct syndrome.

We report three cases of persistent Müllerian duct syndrome, which is a rare form of inherited male pseudohermaphroditism characterized by the presence of a uterus and tubes in otherwise normally virilized 46,XY males. We emphasize the usefulness of ultrasonographic study of the pelvis and inguinal areas in the preoperative diagnosis, which is difficult. We recommend that ultrasound be performed routinely in bilaterally cryptorchid patients.

Adolescent↗
PubMed1993

The persistent müllerian duct syndrome: a rare cause of cryptorchidism.

The persistent Müllerian duct syndrome is characterized by the retention of Müllerian derivatives in patients otherwise normally virilized. Clinically, the persistence of uterus and tubes leads either to cryptorchidism or inguinal hernia, depending on whether or not the Müllerian derivatives can be mobilized during testicular descent. The condition is usually discovered at surgery, however preoperative sonography could allow the diagnosis to be made preoperatively. The molecular basis of the persistent Müllerian duct syndrome is heterogeneous, and is reflected by wide variations in the serum concentration of anti-Müllerian hormone. Some cases are apparently due to end-organ resistance, and are associated with normal serum levels of the hormone. Others, characterized by absent or low hormone concentrations, can be explained by mutations of the gene coding for anti-Müllerian hormone, which are distributed along the whole length of the coding region.

Adolescent↗
PubMed1993

Anti-müllerian hormone in early human development.

Anti-müllerian hormone (AMH) is a glycoprotein produced by immature Sertoli cells and responsible for the regression of müllerian ducts in male fetuses. The ontogeny of the hormone in early human development was investigated. While no detectable AMH could be found in female fetal serum, in males, the mean +/- S.E.M. AMH serum concentration was 40.5 +/- 3.9 ng/ml from 19 to 30 weeks (n = 13), and 28.4 +/- 6.1 ng/ml from 30 weeks to term (n = 9). The latter value is significantly different from the mean AMH concentration in serum from boys aged 2 months to 2 years (43.1 +/- 3.7), suggesting that AMH production is sluggish during the perinatal period. The serum AMH concentration of a 46,XX male fetus was in the normal range for males. Using in situ hybridization, AMH transcripts were detected in the testicular tissue of all fetuses from 8 weeks onwards, but not in fetal ovaries nor in the yet undifferentiated gonadal tissue of a 7-week-old fetus bearing male-determining DNA sequences. Together, these data indicate that AMH is a reliable marker for the presence of functional testicular tissue and, as such, may be helpful for the diagnosis of fetal sex, particularly in the presence of sex chromosome abnormalities.

Amniotic Fluid↗
PubMed1993

Anti-müllerian hormone and testosterone serum levels are inversely during normal and precocious pubertal development.

Anti-Müllerian hormone (AMH), also called Müllerian inhibiting substance or factor, is produced by Sertoli cells from fetal life until puberty. In the present study, AMH, testosterone (T), LH, and FSH were measured by immunochemical methods in the serum of 50 boys with normal or delayed pubertal development, 4 patients with suspected androgen insensitivity, and 11 patients with either central (CPP) or gonadotropin-independent (GIPP) precocious puberty to investigate the hormonal regulatory mechanisms of AMH secretion at puberty. An inverse relationship between AMH and T levels was demonstrated. In boys with normal or delayed puberty with T concentrations below 6.7 nmol/L, AMH values were elevated (mean +/- SEM, 22.4 +/- 3.1 micrograms/L) and widely dispersed. In subjects with T levels over 6.7 nmol/L, AMH levels were uniformly low (3.4 +/- 0.5 micrograms/L), except in patients with suspected androgen insensitivity. No significant relationship was found between AMH and gonadotropin levels. Similar results were obtained in patients with either CPP or GIPP. Longitudinal studies were performed on four boys with CPP and two with GIPP before and after treatment. At the time of diagnosis, the T concentration was high, and AMH levels were usually low in CPP and GIPP patients alike. When appropriate treatment was initiated, the T concentration was normalized within 2-4 weeks, but restoration of prepubertal AMH levels required several months. Mature Sertoli cells were observed in testicular biopsies performed in three patients with untreated GIPP. Our results suggest that gonadotropins are not directly implicated in repression of AMH synthesis at puberty, but, rather, that the decrease in AMH production is the consequence of an androgen-mediated, long term, reversible chain of events leading to morphological and functional maturation of the Sertoli cells. Thus, the fall in serum AMH levels appears to be an excellent marker of Sertoli cell pubertal development.

Adolescent↗
PubMed1993

Mullerian inhibiting substance requires its N-terminal domain for maintenance of biological activity, a novel finding within the transforming growth factor-beta superfamily.

Mullerian inhibiting substance (MIS)/anti-Mullerian hormone is a differentiation factor that causes regression of the Mullerian duct in the developing male fetus and an apparent sex reversal of the fetal ovary when inappropriately exposed to it. The purified product is a 140-kilodalton glycoprotein composed of two identical subunits. We show that a C-terminal fragment of MIS, which shares homology with transforming growth factor-beta, causes regression of the Mullerian duct and inhibits the biosynthesis of aromatase in the fetal ovary. However, both activities are enhanced dramatically by addition of the N-terminal portion of MIS. Under conditions where potentiation occurs, the N- and C-terminal domains of MIS reassociate. These results indicate that the N-terminus of MIS, unlike that of the other members of the transforming growth factor-beta family, plays a role in maintaining the biological activity of the C-terminus.

Animals↗
PubMed1992

Variants of the anti-Müllerian hormone gene in a compound heterozygote with the persistent Müllerian duct syndrome and his family.

The persistent Müllerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism, characterized by the persistence of Müllerian derivatives in otherwise normal males. Two mutations, present in the homozygous state, have been previously described in such patients. The present observation is the first example of compound heterozygosity in this condition. DNA was obtained from a 3-month-old patient with PMDS, in whom no serum anti-Müllerian hormone (AMH) could be detected by enzyme-linked immunosorbent assay. Sequencing of cloned polymerase chain reaction amplified fragments of the AMH gene revealed a 14-bp deletion in the second exon of the maternal allele; this deletion disrupted the open reading frame. It occurred at a site containing two 8-bp direct repeats flanking a 6-bp sequence and removed one whole repeat plus all of the intervening sequence. It may be the result of a slipped mispairing at the DNA replication fork. The paternal allele contains a stop mutation in the third exon. These two mutations, impairing both AMH alleles, are consistent with the occurrence of PMDS, and are shared with a phenotypically normal younger sister. In this family, various other mutations, devoid of physiological significance, suggest that the AMH gene is highly polymorphic.

Adult↗
PubMed1992

Anti-müllerian hormone and Sertoli cell function.

Anti-müllerian hormone (AMH) is a glycoprotein that is produced by immature Sertoli cells and is responsible for the regression of müllerian ducts in male fetuses. It is a useful marker of testicular function in children, when anorchia is suspected and in intersex states. In the persistent müllerian duct syndrome, both AMH-positive and AMH-negative forms have been reported. In three cases of the latter, a mutation of the AMH gene is thought to have been responsible for the condition.

Animals↗
PubMed1992

A quantitative and interspecific test for biological activity of anti-müllerian hormone: the fetal ovary aromatase assay.

Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting substance or factor, has previously been shown to sex-reverse the steroidogenic pattern of fetal mammalian ovaries through repression of aromatase biosynthesis. Study of the ontogeny of the response of cyclic AMP-stimulated aromatase activity of rat fetal ovaries to AMH has allowed us to develop a quantitative bioassay for the hormone. Linear responses as a function of the logarithm of AMH concentration were observed over ranges of 0.2-7.5 micrograms/ml for the bovine protein and 0.15-2 micrograms/ml for the human protein, with a maximal decrease in aromatase activity of 90% for both proteins. Under the same in vitro conditions, AMH treatment did not affect cyclic AMP-stimulated fetal rat testicular aromatase activity. Partially purified chick AMH also decreased rat ovarian aromatase activity, allowing us to use this test to study AMH ontogeny in chick gonads. Analysis of the species specificity of AMH repression of ovarian aromatase activity indicated that turtle and rat fetal ovaries responded to AMH of other vertebrate classes, whereas aromatase activity of chick embryo ovaries could be repressed only by the homospecific hormone.

Animals↗
PubMed1991

Anti-Müllerian hormone Bruxelles: a nonsense mutation associated with the persistent Müllerian duct syndrome.

The persistent Müllerian duct syndrome (PMDS) is characterized by the persistence of Müllerian derivatives, uterus and tubes, in otherwise normally virilized males. In a previous study, we showed that this syndrome is heterogeneous, with lack of production of anti-Müllerian hormone (AMH) by testicular tissue accounting for only some, AMH-negative, cases of this disorder. We have characterized the point mutation responsible for an AMH-negative PMDS in three siblings: a guanine to thymine transversion at position 2096 in the fifth exon changes a GAA triplet, coding for glutamic acid, to a TAA stop codon. The mutation could also be recognized, using the polymerase chain reaction, on RNA produced in trace amounts by a lymphoblastic cell line. The translation product, although undetectable in testicular tissue, could be visualized in culture medium of cells transfected with the mutant gene.

Anti-Mullerian Hormone↗
PubMed1991

[Anti-mullerian hormone and natural and experimental freemartin effect].

To determine whether anti-Müllerian hormone (AMH) is responsible for the gonadal anomalies observed in bovine female "freemartins" united by placental anastomosis to a male twin, fetal rat and ovine prospective ovaries were exposed to purified bovine AMH in organ culture. We show that AMH reproduces the caracteristical "freemartin effect"; namely the initial inhibition of gonadal and germ cell development, and the differentiation of fetal Sertoli cells forming seminiferous cord-like structures and producing immuno and bioactive AMH. In addition, fetal ovine ovaries submitted to AMH release testosterone instead of estradiol due to an inhibiting effect upon the biosynthesis of their aromatase enzyme. Taken together, these results indicate that AMH is probably the testicular factor responsible for the abnormalities of freemartin gonads and suggest that this hormone could play a pivotal role in normal testis differentiation.

Animals↗
PubMed1991

Anti-Müllerian hormone in three intersex conditions.

Anti-Müllerian hormone (AMH), secreted by embryonic testicular Sertoli cells, inhibits the development of Müllerian ducts in the male. An enzyme-linked immunoassay (ELISA) for AMH was used to investigate three intersex infants. The AMH level was correlated with each patient's degree of Müllerian duct development. Complete inhibition of Müllerian structures correlated with the normal levels of AMH in the infant with testicular feminization. Detectable levels of AMH were found in the hermaphroditic infant; however, these low levels reflected Sertoli cell inadequacy of the ovotestis, which was documented by a right rudimentary Fallopian tube and a normal uterus. In the infant with persistent Müllerian duct syndrome, (PMDS), the normal Müllerian derivatives are compatible with 1) an AMH receptor defect; 2) a biologically and immunologically abnormal AMH molecule, or 3) a functional AMH deletion. The lack of detectable AMH in this infant excluded the AMH receptor abnormality and thus directed authors' search for the specific defect to the AMH gene. Thus, this ELISA for AMH is as valuable a tool to the molecular biologist studying a precise genetic error as it is to the physician making a precise clinical diagnosis.

Anti-Mullerian Hormone↗
PubMed1991

[Molecular biology of normal and pathologic anti-müllerian hormone].

Anti-Müllerian hormone, responsible for Müllerian regression in male fetuses, is a glycoprotein dimer with two 72 kD subunits. The AMH gene is a small (2,800 bp) gene with 5 exons, localized on the tip of the short arm of chromosome 19, band p 133, and transcribed in a 2,000 kbp mRNA. Persistent Müllerian duct syndrome, a rare form of male pseudohermaphroditism characterized by the presence of uterus and Fallopian tubes in patients with normally virilized genitalia, may result from defective AMH gene or from target-organ insensitivity. Four mutations were identified in the AMH gene, 3 are point mutations (2 stop codons, the third altering the secondary structure of the molecule), the last is a 14 bp deletion, leading to alteration of the reading frame of the mRNA.

Anti-Mullerian Hormone↗
PubMed1990

Anti-müllerian hormone: hormone or growth factor?

Anti-Müllerian hormone (AMH) is a dimeric glycoprotein member of the TGF-beta family. It is synthesized by immature Sertoli cells, and, to a lesser degree, by adult Sertoli and granulosa cells. AMH is responsible for the regression of Müllerian ducts in the male fetus; it also has deleterious effects on the female fetal reproductive tract, destroying Müllerian primordia and germ cells, and masculinizing the fetal ovary on the rare occasions female fetuses become exposed to its effects. All other suggested actions for AMH--retardation of oocyte meiosis, inhibition of EGF receptor autophosphorylation, anti-cancer activity--have been reported with crude hormone preparations, and have not been confirmed using pure AMH. Its relatively limited sphere of action--the fetal genital tract--and the fact that it is secreted into the general circulation and can act at long range, imply that AMH is more like a hormone than a growth factor, but the complex interaction between hormones and growth factors make a formal distinction impossible.

Amino Acid Sequence↗
PubMed1990

An enzyme linked immunoassay for anti-müllerian hormone: a new tool for the evaluation of testicular function in infants and children.

Anti-Müllerian hormone (AMH), also called Müllerian-inhibiting substance or factor was measured by an interspecific enzyme-linked immunoassay in the serum of 218 normal children and adults of both sexes and in 110 boys with various developmental disorders. AMH levels were high [81.67 ng/ml +/- 7.44(SEM)] in normal males under 2 yr of age, fell progressively in older boys and, decreased sharply at puberty. Serum AMH was not detectable in adults or in females at any age, with very rare exceptions. AMH serum concentrations were significantly decreased in infants with disorders of sex differentiation, particularly testicular dysgenesis, and increased in patients with delayed puberty. In contrast, levels were not significantly affected by either cryptorchidism or chorionic gonadotropin stimulation. AMH shows promise as a marker of testicular function in infancy.

Adolescent↗