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S Christin-Maitre

Publications and source records attributed to S Christin-Maitre.

At least 19 recordsLinked to original sources
PubMed2006

Molecular cytogenetic studies of Xq critical regions in premature ovarian failure patients.

BACKGROUND: Premature ovarian failure (POF) is defined as amenorrhoea for more than 6 months, occurring before the age of 40, with an FSH serum level higher than 40 mIU/ml. Cytogenetically visible rearrangements of the X chromosome are associated with POF. Our hypothesis was that cryptic Xq chromosomal rearrangements could be an important etiological contributor of POF. METHODS: Ninety POF women were recruited and compared to 20 control women. Peripheral blood samples were collected and metaphase chromosomes were prepared using standard cytogenetic methods. To detect Xq chromosomal micro-rearrangements, fluorescence in situ hybridization (FISH) analysis was performed using a selection of 30 bacterial artificial chromosome (BAC) and P1 artificial chromosome clones, spanning Xq13-q27. We further localized the translocation breakpoints by FISH with additional BAC clones. RESULTS: Chromosomal abnormalities were identified in 8.8% of our 90 patients [one triple X, three large Xq deletions 46,X,del(X)(q22.3), 46,X,del(X)(q21.2) and 46,X,del(X)(q21.32), two balanced X;autosome translocations 46,X,t(X;1) (q21.1;q32) and 46,X,t(X;9)(q21.31;q21.2) and two Robertsonian translocations 45,XX,der(15;22)(q10;q10) and 45,XX,der(14;21)(q10;q10)]. The two Xq translocation breakpoints were among a cluster of repetitive elements without any known genes. FISH analysis did not reveal any Xq chromosomal micro-rearrangement. CONCLUSIONS: Karyotyping is definitely helpful in the evaluation of POF patients. No submicroscopic chromosomal rearrangements affecting Xq region were identified. Further analysis using DNA microarrays should help delineate Xq regions involved in POF.

Adult↗
PubMed2006

[Premature ovarian failure].

Premature ovarian failure (POF) is defined by at least four months of amenorrhea with elevated gonadotropins (usually above 40 UI/L) detected on two occasions a few weeks apart, in a woman before the age of 40. It occurs in 1 out of 10,000 in women below the age of 20, 1/1,000 below 30 and 1% in women before the age of 40. In 80% of POF cases, the etiology is unknown, except for Turner syndrome. The different etiologies identified are 1) iatrogenic following chemotherapy and/or radiotherapy, 2) autoimmune, 3) viral, 4) genetic (RFSH, FOXL2, FRAXA, BMP15, GDF9, GALT, 17 hydroxylase...). Management of these patients includes hormone replacement therapy in order to avoid an increase in cardiovascular risk and osteoporosis related to hypoestrogenism. Infertility is common, as only 3 to 10% of the patients will have natural conception. When fertility is desired, women with POF should be oriented towards oocyte donation centers. Research is currently performed in order to identify new genes involved in POF.

Adult↗
PubMed2006

[Intra-alveolar hemorrhage revealing pheochromocytoma].

We report a case of pheochromocytoma revealed by alveolar hemorrhage in a 51-year-old woman. Pheochromocytomas are rare tumors deriving from the chromaffin tissue, and which clinical manifestations are highly variable, mostly unspecific, and very rarely concern the lung. Therefore, the diagnosis is often missed or delayed. However, without correct diagnosis and subsequently adapted treatment, the disease may be fatal. Thus, clinicians should be aware of the possible diagnosis of pheochromocytoma in patients presenting hemoptysis of an unknown origin.

Adrenal Gland Neoplasms↗
PubMed2005

Deletions involving long-range conserved nongenic sequences upstream and downstream of FOXL2 as a novel disease-causing mechanism in blepharophimosis syndrome.

The expression of a gene requires not only a normal coding sequence but also intact regulatory regions, which can be located at large distances from the target genes, as demonstrated for an increasing number of developmental genes. In previous mutation studies of the role of FOXL2 in blepharophimosis syndrome (BPES), we identified intragenic mutations in 70% of our patients. Three translocation breakpoints upstream of FOXL2 in patients with BPES suggested a position effect. Here, we identified novel microdeletions outside of FOXL2 in cases of sporadic and familial BPES. Specifically, four rearrangements, with an overlap of 126 kb, are located 230 kb upstream of FOXL2, telomeric to the reported translocation breakpoints. Moreover, the shortest region of deletion overlap (SRO) contains several conserved nongenic sequences (CNGs) harboring putative transcription-factor binding sites and representing potential long-range cis-regulatory elements. Interestingly, the human region orthologous to the 12-kb sequence deleted in the polled intersex syndrome in goat, which is an animal model for BPES, is contained in this SRO, providing evidence of human-goat conservation of FOXL2 expression and of the mutational mechanism. Surprisingly, in a fifth family with BPES, one rearrangement was found downstream of FOXL2. In addition, we report nine novel rearrangements encompassing FOXL2 that range from partial gene deletions to submicroscopic deletions. Overall, genomic rearrangements encompassing or outside of FOXL2 account for 16% of all molecular defects found in our families with BPES. In summary, this is the first report of extragenic deletions in BPES, providing further evidence of potential long-range cis-regulatory elements regulating FOXL2 expression. It contributes to the enlarging group of developmental diseases caused by defective distant regulation of gene expression. Finally, we demonstrate that CNGs are candidate regions for genomic rearrangements in developmental genes.

Animals↗
PubMed2003

A comparative randomized multicentric study comparing the step-up versus step-down protocol in polycystic ovary syndrome.

BACKGROUND: The aim of the study was to evaluate follicular development and ovulation comparing the low-dose step-up and the step-down protocols, in women with clomiphene citrate (CC)-resistant polycystic ovaries. METHODS: Eighty-three women were randomized, and treated with recombinant (r) FSH (Puregon) using either the step-up (n=44) or step-down (n=39) protocol. They were followed up for three cycles unless pregnancy occurred. RESULTS: Monofollicular development occurred in 68.2% of the 85 cycles in the step-up group, as compared with 32% of the 72 cycles in the step-down group (P<0.0001). Hyperstimulation was statistically less frequent using the step-up procedure (4.7 versus 36%, P<0.0001). Both protocols used the same number of FSH units per cycle (951+/-586 versus 967+/-458 in step-up and step-down respectively, P=not significant). However, the duration of ovarian stimulation was statistically different (15.2+/-7.0 days in step-up versus 9.7+/-3.1 in step-down, P<0.001). Ovulation was observed in 70.3% of the cycles using the step-up procedure as compared with 51.3% using the step-down procedure (P<0.01). The cumulative rate of clinical gestations during the study did not differ between the two groups (38.6% in the step-up versus 30.8% in the step-down procedure). CONCLUSIONS: The step-up protocol using rFSH (Puregon), is more efficient in obtaining a monofollicular development and ovulation than the step-down protocol, in women with CC-resistant polycystic ovaries. Although the duration of stimulation is longer, the rate of ovarian hyperstimulation is much lower using the step-up protocol.

Adult↗
PubMed2003

A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy.

A-Type lamins, arising from the LMNA gene, are intermediate filaments proteins that belong to the lamina, a ubiquitous nuclear network. Naturally occurring mutations in these proteins have been shown to be responsible for several distinct diseases that display skeletal and/or cardiac muscle or peripheral nerve involvement. These include familial partial lipodystrophy of the Dunnigan type and the mandibuloacral dysplasia syndrome. The pathophysiology of this group of diseases, often referred to as laminopathies, remains elusive. We report a new condition in a 30-yr-old man exhibiting a previously undescribed heterozygous R133L LMNA mutation. His phenotype associated generalized acquired lipoatrophy with insulin-resistant diabetes, hypertriglyceridemia, hepatic steatosis, hypertrophic cardiomyopathy with valvular involvement, and disseminated whitish papules. Immunofluorescence microscopic analysis of the patient's cultured skin fibroblasts revealed nuclear disorganization and abnormal distribution of A-type lamins, similar to that observed in patients harboring other LMNA mutations. This observation broadens the clinical spectrum of laminopathies, pointing out the clinical variability of lipodystrophy and the unreported possibility of hypertrophic cardiomyopathy and skin involvement. It emphasizes the fact that the diagnosis of genetic alterations in A-type lamins requires careful and complete clinical and morphological investigations in patients regardless of the presenting signs.

Adult↗
PubMed2003

Pharmacodynamics of follicle stimulating hormone (FSH) in postmenopausal women during pulsed estrogen therapy: Evidence that FSH release and synthesis are controlled by distinct pathways.

17 beta-Estradiol (E2) exerts negative feedback effects at the hypothalamo-pituitary level on serum FSH. This study investigated the effects of repeated daily administration of intranasal E2 (S21400) on the pharmacokinetics (PK) of E2 and estrone (E1) and the pharmacodynamics (PD) of FSH and assessed the PK/PD relationship between E2 and FSH using population model-dependent analysis. Postmenopausal volunteers (n = 24) received according to a balanced cross-over design, two 28-d treatments separated by a 2-month wash-out period: 300 microg E2, either alone or combined with oral dydrogesterone (20 mg/d) during the last 14 d of one of the treatments. Absorption of E2 was rapid, with maximal plasma concentrations at 10-30 min, returning to postmenopausal levels within 12 h. Over the 24-h period, FSH levels showed a U curve, with a minimum around 8 h after E2 administration. Moreover, over the treatment period, FSH basal values decreased by 17% between d 1 and 14 and an additional 5% between d 14 and 28. A PK/PD model described these short- and mid-term effects, possibly reflecting separate regulation mechanisms by E2 on FSH release and biosynthesis, respectively. The administration of progestin had no influence on E1, E2, and FSH model parameters. This study suggests that daily transient tissue exposure to E2 after pulsed estrogen therapy elicits short- and mid-term effects on the gonadotropin axis.

Administration, Intranasal↗
PubMed2002

Mixed ductal-pancreatic polypeptide-cell carcinoma of the pancreas.

AIMS: Mixed ductal-endocrine carcinomas of the pancreas are rare tumours with 10 cases reported in the English literature. We report the first case with a polypeptide-cell component. METHODS AND RESULTS: : The tumour was fortuitously discovered in a 72-year-old woman during the exploration of an endometrial adenocarcinoma. It measured 100 mm and was located in the tail of the pancreas. On microscopic examination two intermingled endocrine and exocrine components were present. The endocrine component consisted of trabeculae and solid nests composed of cells immunoreactive for chromogranin A, synaptophysin and pancreatic polypeptide, but negative for p53 and Bcl-2 proteins. The exocrine component was composed of tubules lined by atypical cylindrical cells immunoreactive for CK19, CEA, p53 and Bcl-2. The stroma of the endocrine component contained amyloid deposits. CONCLUSION: Mixed ductal-endocrine carcinomas of the pancreas are often described in middle-aged patients. The tumours are usually large and located in the head of the pancreas. An endocrine syndrome is rare and the prognosis is often unfavourable. We report the first case of mixed endocrine-exocrine carcinoma of the pancreas with a pancreatic polypeptide-cell component. The histogenesis of mixed carcinoma of the pancreas is still uncertain but the over-expression of p53 and Bcl-2 could play a major role in the neoplastic progression of the ductal component.

Adenocarcinoma↗
PubMed2000

Bioassays of gonadotropins.

Bioassays constitute a unique approach to determine the functional aspects of gonadotropins. Indeed, these highly complex glycoprotein hormones, including pituitary lutropin (LH) and follitropin (FSH), are heterogeneous in terms of both peptidic and carbohydrate moieties, and, as a consequence, the bioactivity of the different molecular forms often does not match their immunoreactivity. In this article, we review the different types of LH and FSH bioassays. Conventional methods for measuring FSH bioactivity are first described and include the in vivo Steelman and Pohley bioassay, the radioligand receptor assays (RRAs), the in vitro Sertoli cell bioassay, the in vitro granulosa cell bioassay, and the inhibin immunoassay. Recent methods based on cell lines transfected with cloned receptors, particularly the human FSH receptor, are then described. Methods for developing these assays are presented, and the advantages and disadvantages of the different bioassays are discussed.

Animals↗
PubMed2000

A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism.

Mutations in the DAX1 gene cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). In affected boys, primary adrenal insufficiency occurs soon after birth or during early childhood; HHG is recognized at the expected time of puberty. In this report, we describe the novel phenotype of a man who presented with apparently isolated adrenal insufficiency at 28 years of age. Examination revealed partial pubertal development and undiagnosed incomplete HHG. Gonadotropin therapy did not improve his marked oligospermia, suggesting a concomitant primary testicular abnormality. Genomic analysis revealed a novel missense mutation, I439S, in DAX1. The mutant DAX-1 protein was studied for its ability to function as a transcriptional repressor of target genes. Consistent with the patient's mild clinical phenotype, the I439S mutation conferred intermediate levels of repressor activity of DAX-1 when compared with mutations associated with classic AHC. This unique case extends the clinical spectrum of AHC to include delayed-onset primary adrenal insufficiency in adulthood and milder forms of HHG. Furthermore, in accordance with findings in Ahch (Dax1) knockout mice, the clinical features in this patient suggest that DAX-1 function is required for spermatogenesis in humans, independent of its known effects on gonadotropin production.

Adrenal Glands↗
PubMed2000

Effect of gonadotrophin-releasing hormone (GnRH) antagonist during the LH surge in normal women and during controlled ovarian hyperstimulation.

OBJECTIVE: Several studies have suggested that GnRH is instrumental in triggering the LH surge. The present studies were performed to evaluate the effect of GnRH antagonist administration in women after the beginning of the LH surge. DESIGN: In study one, six normal cycling women were given a GnRH antagonist (20 mg Nal Glu s.c.) during an unstimulated cycle. Nal-Glu was administered when the LH level was higher than 10 U/l and associated with an oestradiol (E2) level higher than 730 pmol/l. In study two, a GnRH antagonist (3 mg Cetrorelix, ASTA-Medica, Frankfurt, Germany) was administered on day 8 of an IVF-ET cycle, in 157 women. Eighteen women among this cohort received the antagonist, when their LH level was higher than 10 U/l. RESULTS: In normal volunteers (study one), Nal-Glu was administered on day 13.7 +/- 1.4 (mean +/- SD) of the cycle when the LH level was 13.7 +/- 3.5 U/l with an E2 plasma level reaching 980 +/- 131 pmol/l. Twenty-four hours after administration of the antagonist, the LH surge had been interrupted in all subjects; it was postponed in three of the women, and abolished in the remaining three. LH levels fell by 68.5%, E2 by 42% and FSH by 53.2%. In study two, LH plasma levels 24 h after the antagonist administration fell by 94%. No premature ovulation occurred in any of the patients treated. Administering the antagonist before (n = 139) or during the LH surge (n = 18) made no statistically significant difference to the results of the IVF-ET attempt. CONCLUSIONS: Our results indicate that GnRH is required throughout the gonadotrophin surge in women, not only for the initiation but also for the maintenance of the LH surge. In addition, in our study, the suppression of the rise in LH, when the antagonist was given during the surge, had no detrimental impact on IVF-ET outcome. This suggests, if confirmed on a larger scale, that late follicular phase GnRH antagonist administration to prevent the LH surge in controlled ovarian hyperstimulation (COH) is a safe and useful treatment.

Adult↗
PubMed1999

[Premature ovarian insufficiency].

Premature ovarian failure is defined as amenorrhea with hypo-oestrogenism and elevated gonadotrophins occurring before the age of 40 years. In theory, ovarian failure may occur because of a decreased pool of primordial follicles, because ovarian apoptosis is increased or accelerated or because the follicle maturation is interrupted before the preovulatory stage. The mechanisms inducing premature ovarian failure have been described in a few number of cases. Atm or c-kit gene mutations induce a very low pool of primordial follicles. In chromosome X abnormalities, chemotherapy, galactosemia and blepharophimosis syndrome apoptosis is increased. Follicle maturation is interrupted in FSH and LH receptor mutations or in autoimmunity. However, in most cases, the etiology remains idiopathic. A better knowledge in genes involved in ovarian apoptosis should enhance our understanding of premature ovarian failure. Meanwhile, the best treatment is to give hormonal replacement therapy and send the patient to oocyte donation program when they desire to be pregnant.

Adult↗
PubMed1999

Main inhibitor of follicle stimulating hormone in the luteal-follicular transition: inhibin A, oestradiol, or inhibin B?

The roles of oestradiol, inhibin A and inhibin B in the luteal-follicular transition were assessed by means of specific assays. Six premenopausal women were studied during a control and then a cycle treated with percutaneous oestradiol 0.1 mg/day from day 10 after the luteinizing hormone (LH) surge until day 4 of the following cycle. Inhibin A concentrations decreased similarly in control and treated cycles from day -5 to day 2, then increased in control cycle to 23.3 +/- 3.4 pg/ml on day 10 (mean +/- SEM). They remained low until day 5 in treated cycles and were lower than controls on day 10 (P < 0.01). Follicle stimulating hormone (FSH) concentrations increased on day 1 in controls and on day 5 in treated cycles when oestradiol concentration fell abruptly. Inhibin B concentrations remained low until day 1 in controls and day 4 in treated cycles. In both, inhibin B concentrations increased 1 day after FSH, peaking at 160 pg/ml. FSH concentrations began to plateau when inhibin B concentrations were >100 pg/ml and oestradiol concentrations below 200 pmol/l. These data suggest that inhibin A is not responsible for FSH suppression in the luteal phase and that the negative control of FSH shifts from oestradiol in the luteal phase to inhibin B in the mid-follicular phase.

Adult↗
PubMed1999

Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration.

We have studied a kindred with three siblings with isolated hypogonadotropic hypogonadism caused by compound heterozygote mutations in the GnRH receptor gene. The disorder was transmitted as an autosomal recessive trait. The R262Q mutation in intracellular loop 3 of the receptor was associated with a mutation in the third transmembrane domain of the receptor, A129D, that has never been described before. This A129D mutation results in a complete loss of function, indicated by the lack of inositol triphosphate (TP3) 3 production by transfected Chinese hamster ovary (CHO) cells after GnRH stimulation. The two brothers had microphallus and bilateral cryptorchidism and were referred for lack of puberty, whereas their sister had primary amenorrhea and a complete lack of puberty. Their basal gonadotropin concentrations were below the reference range, and their endogenous LH secretory patterns were abnormal, with a low-normal frequency of small pulses or no apparent LH pulse. Pulsatile GnRH administration (10 microg/pulse every 90 min for 40 h) resulted in increased mean LH without any significant changes in testosterone levels in the two brothers, whereas the LH secretory profile of their sister remained apulsatile. Larger pulses of exogenous GnRH (20 microg every 90 min for 24 h) caused the sister to produce recognizable low amplitude LH pulses. The concentrations of free alpha-subunit significantly increased in all patients during the pulsatile GnRH administration. Thus, these hypogonadal patients are partially resistant to pulsatile GnRH administration, suggesting that they should be treated with gonadotropins to induce spermatogenesis or ovulation rather than with pulsatile GnRH.

Adolescent↗