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J Y Picard

Publications and source records attributed to J Y Picard.

At least 37 records · Page 2Linked to original sources
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↗
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↗
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

[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

Expression of the gene for anti-Müllerian hormone.

The expression of anti-Müllerian hormone, also called Müllerian-inhibiting substance or factor, is limited to immature Sertoli and post-natal granulosa cells. To gain information on the genetic mechanisms of this tissue- and development-specific regulation, a human genomic clone containing 3.6 kilobases of 5' flanking sequences has been isolated and sequenced. Transcription initiation sites include a major site, at the same position as in the bovine gene, and 3 minor sites, accounting together for 12% of transcripts. Sequences of potential interest include an Sp1 binding site, minisatellite-like regions, and a 13-base pair palindrome, nearly identical to the oestrogen response element of the vitellogenin genes. This palindrome binds to the human oestrogen receptor in vitro and activates transcription of a hybrid gene when several copies are inserted 5' of a thymidine kinase promoter. Further studies are needed to determine whether this palindrome is implicated in a feed-back loop regulating oestrogen synthesis in granulosa cells.

Anti-Mullerian Hormone↗
PubMed1989

The persistent Müllerian duct syndrome: a molecular approach.

A rare form of male pseudohermaphroditism is characterized by the persistence of Müllerian derivatives in phenotypic males. To determine the etiology of this syndrome, we studied the expression of anti-Müllerian hormone (AMH) in six boys, including three brothers, with the persistent Müllerian duct syndrome. All except one presented with an inguinal hernia containing the Müllerian derivatives, and in two boys the hernial sac contained the contralateral testis. AMH was normally expressed in the testicular tissue of two patients, as shown by bioassay of anti-Müllerian activity and immunocytochemistry. The testicular tissue of the other patients had no detectable bioactive or immunoreactive AMH, yet they expressed AMH mRNA with a normal transcription initiation site and in the amount expected for their age. These results prove the heterogeneity of the persistent Müllerian duct syndrome and suggest that it may sometimes involve peripheral insensitivity to AMH.

Animals↗
PubMed1988

Immunopurified anti-müllerian hormone does not inhibit spontaneous resumption of meiosis in vitro of rat oocytes.

The ability of immunopurified, biologically potent anti-Müllerian hormone (AMH) to inhibit the spontaneous resumption of meiosis of rat oocytes was tested in vitro. Two different batches of AMH in the range of 0.75-9.0 micrograms/protein did not suppress the spontaneous resumption of meiosis. Neither did AMH (6 micrograms/ml) induce meiotic resumption of follicle-enclosed oocytes in culture. It is concluded, therefore, that AMH has no oocyte meiosis-inhibiting activity.

Animals↗
PubMed1988

A monoclonal antibody against human testicular anti-müllerian hormone.

Using immunochromatography on a polyclonal antibody, testicular anti-Müllerian hormone (AMH) was purified from homogenates of human fetal testicular tissue and used as an antigen for hybridoma production. Two IgM clones were obtained. Both recognized AMH on biopsies of human testicular tissue and one blocked its anti-Müllerian activity. This monoclonal antibody (MAb) exhibited a relatively high affinity for AMH, and was studied further. It is interspecific, recognizing AMH in other mammalian species. The study of this MAb in relation to an IgM MAb raised against bovine AMH (bAMH) indicates that both MAbs recognize different but related epitopes on bAMH.

Anti-Mullerian Hormone↗
PubMed1987

Immunocytochemical detection of anti-müllerian hormone in Sertoli cells of various mammalian species including human.

An immunocytochemical method, based on the use of a polyclonal antibody raised against purified bovine anti-Müllerian hormone (AMH), was used to detect AMH in Sertoli cell cytoplasm of various mammalian species, including human. Immunopurification of antiserum by AMH-affinity chromatography, although not mandatory, leads to better results and increased sensitivity. In human testicular tissue, AMH is detectable up to 6 years of age. In rats, AMH production is initiated at 13 days post coitum, peaks between 15 and 17 days, and is no longer detectable 1 week after birth. The reaction is strongest in Sertoli cells of calves, sheep, goats, and pigs, species characterized by a high degree of development of the rough endoplasmic reticulum. It is fainter in human, rat, rabbit, and cat Sertoli cells, in which the rough endoplasmic reticulum is not as abundant. This correlation is not unexpected, in view of the localization of reaction product in this cytoplasmic organelle. Preliminary results indicate that there may be a relationship between the amount of immunoreactive AMH present in testicular biopsies of intersex patients and the degree of regression of the Müllerian duct on the ipsilateral side. This may help to elucidate whether persistence of Müllerian ducts results from lack of testicular production of AMH or from peripheral resistance of the Müllerian primordia to the hormone.

Animals↗
PubMed1986

Biochemical analysis of bovine testicular anti-Müllerian hormone.

Direct biochemical analysis has been applied to bovine testicular anti-Müllerian hormone (AMH), purified from incubation medium of bovine fetal testes by immunochromatography on a monoclonal antibody. The hormone contains a high proportion of hydrophobic amino acids and 13.5% carbohydrate. The oligosaccharide composition suggests that both N- and O-glycosidically linked chains are present. The molecular extinction coefficient is 3.27 +/- 0.06. One RIA unit, defined as the amount of hormone released by 1 g fetal bovine testicular tissue incubated during 4 h, corresponds to 3.06 +/- 0.17 microgram protein.

Amino Acids↗
PubMed1986

Persistence of müllerian ducts in male rabbits passively immunized against bovine anti-müllerian hormone during fetal life.

A female rabbit was immunized against purified bovine AMH and mated. Booster injections were given at Day 8 of pregnancy to ensure a high titer of anti-AMH antibodies at the time the rabbit fetal testis begins to produce AMH. In three consecutive litters, the immunized female produced a total of 12 males, 9 of which had persistent Müllerian duct derivatives. No other significant abnormalities were detected in these animals, which were compared to the offspring of a control saline-injected female. In particular, testicular morphology was normal in most animals, and serum FSH levels did not differ from controls. This experimental model lends no support to the hypothesis that AMH controls extra-Müllerian events of male sex differentiation, nor that of the existence of a regulatory mechanism for synthesis of AMH by Sertoli cells, but it does not definitely exclude these possibilities, inasmuch as our tentative conclusions are based upon study of only one immunized female.

Animals↗
PubMed1986

Cloning and expression of cDNA for anti-müllerian hormone.

Messenger RNA, prepared from fetal bovine testicular tissue, was used to construct a cDNA library in lambda gt11 phage. The library was screened with an antibody probe directed against bovine anti-Müllerian hormone and three positive clones were isolated. Cross-hybridizing cDNA inserts carried by clones 4 and 5 (1.2 and 0.08 kilobases long, respectively) code for a fragment of authentic anti-Müllerian hormone, as shown by the ability of the anti-epitope antibodies eluted from fusion protein 4 to bind strongly to anti-Müllerian hormone on immunoblots and by the capacity of anti-epitope antibodies 4 and 5 to precipitate radioiodinated bovine anti-Müllerian hormone. A probe prepared from insert 4 hybridizes with an mRNA present only in tissues that are known producers of anti-Müllerian hormone, such as the fetal testis and adult ovarian follicles. The amount of specific mRNA in tissues of males and females is related to the rate of their anti-Müllerian hormone production. The 2.1-kilobase size of this mRNA species is large enough to code for the Mr 62,000 anti-Müllerian hormone polypeptide chain. Insert 4 also hybridizes with an mRNA of similar size in human and rat fetal testicular tissue. The third isolated clone, clone 8, which does not cross-hybridize with the others, carries a cDNA insert coding for a ubiquitous protein, smaller than anti-Müllerian hormone, with which it apparently shares an epitope.

Animals↗
PubMed1986

Monoclonal antibodies raised against bovine anti-müllerian hormone: bovine, ovine, and caprine hormones share a set of identical epitopes.

Monoclonal antibodies (Mabs) have been raised against purified bovine anti-Müllerian hormone (bAMH) in an effort to obtain nonzoospecific reagents. Although the majority of the resulting hybridomas resembled those obtained previously insofar as they recognized only bovine, ovine and caprine AMH, four others, all immunoglobulin Ms, were directed against an epitope shared with AMH of other species, namely rabbit, pig and cat. Both the zoospecific and the conserved epitopes were located close to the site required for biological activity. It is suggested that the similarity between the immunogenic characteristics of bovine, ovine and caprine AMH is in some way related to the fact that AMH in these species is disseminated in the blood stream and may produce freemartinism.

Animals↗
PubMed1985

Secretion of anti-Müllerian hormone by immature bovine Sertoli cells in primary culture, studied by a competition-type radioimmunoassay: lack of modulation by either FSH or testosterone.

Secretion of anti-Müllerian hormone (AMH) by immature bovine Sertoli cells in primary culture was studied through a competition-type RIA employing a polyclonal antibody and 125I-labelled purified AMH. This RIA is approximately 10 times more sensitive than the solid-phase two-site monoclonal antibody-based RIA described previously. Biosynthesis and secretion of AMH by cultured Sertoli cells require approximately 48 h, are not influenced by FSH or testosterone and steadily decrease over a one-week period of culture. Cyclic AMP response to FSH stimulation is normal in cultured cells. Whether the factors responsible for the extinction of AMH production in vitro are in any way related to those operating during normal maturation, which lead to repression of AMH biosynthesis in adult Sertoli cells, is not known at the present time and deserves further study.

Age Factors↗