Biomedical subjects

Charles Sultan

Publications and source records attributed to Charles Sultan.

39 records · Page 3Linked to original sources

PubMed2002

Postnatal changes of T, LH, and FSH in 46,XY infants with mutations in the AR gene.

Androgen insensitivity syndromes (AIS) result from the incapacity for T and dihydrotestosterone to virilize male embryos and is mainly attributable to molecular defects of the AR gene. In normal males, T and LH rise during the first few months of life, and this physiological surge is commonly used to evaluate the gonadotropic axis at this age. This neonatal surge has not been evaluated in detail in newborns with AIS. We sequentially measured plasma T, LH, and FSH during the first 3 months of life in 15 neonates with AIS and AR mutation. A GnRH and an human CG stimulation test were also performed. Patients were divided in 2 groups with complete (n = 10) or partial (n = 5) AIS (CAIS or PAIS), based on the clinical phenotype. In patients with PAIS, T levels were in the high-normal range at d 30 (18.4 +/- 6.9 nM) and d 60 (12.8 +/- 3.8 nM). In contrast, plasma T values were below the normal range in 9 of 10 patients with CAIS at d 30 (1 +/- 0.3 nM) and d 60 (1.4 +/- 0.7 nM, both P < 0.004 vs. PAIS). Plasma LH values were low in CAIS at d 30 (0.7 +/- 0.1U/liter) and increased normally in PAIS (8.7 +/- 2.5 U/liter, P = 0.004). We conclude that the postnatal T and LH surge occurs expectedly in neonates with PAIS but is absent in those with CAIS and that the postnatal T rise requires the receptivity of the hypothalamo-pituitary axis to T.

Androgen-Insensitivity Syndrome↗

PubMed2002

A new recombinant cell bioassay for ultrasensitive determination of serum estrogenic bioactivity in children.

The evaluation of estrogenic status is necessary for many physiological and pathological conditions in pediatric as well as adult endocrinology. Because current immunoassays exclusively measure E2--and with a sensitivity that is insufficient for prepubertal children--we developed a new recombinant cell bioassay for ultrasensitive determination of serum estrogenic bioactivity. This assay is based on human uterine cervix carcinoma cells, HeLa cells, that do not naturally express E2 receptor. These cells were transfected with plasmids encoding the human ERalpha or beta, along with an estrogen-responsive promoter fused to the luciferase gene, and called HELNalpha and HELNbeta for HeLa estrogen-responsive element luciferase neomycin alpha and beta. HELNalpha and HELNbeta are able to respond to estrogens and various compounds having estrogenic activity but, because of the importance of ERalpha in the reproductive function, we chose to work with the HELNalpha cell line. The luciferase activity we obtained was compared with an E2 standard curve specific for each serum sample and established with stripped serum. The estrogenic bioactivity was expressed in picograms of E2 equivalents, and the detection limit was < 1 pg x ml(-1) E2 equivalents. The intra and interassay error was lower than 10% and 20%, respectively. We measured estrogenic bioactivity in 18 normal prepubertal boys (age = 9.7 +/- 2.4 yr), 18 normal prepubertal girls (age = 9.2 +/- 1.7 yr) and 18 normal pubertal girls (age = 13.6 +/- 1.8 yr). The estrogenic bioactivity in the prepubertal girls was significantly higher than in the boys, i.e. 3.53 +/- 2.23 pg x ml(-1) vs. 1.44 +/- 0.87 pg x ml(-1) (P < 0.01). A significant difference was found between the pre- and pubertal girls, i.e. 3.53 +/- 2.23 pg x ml(-1) vs. 26.77 +/- 18.32 pg x ml(-1) (P < 0.01). This ultrasensitive bioassay measures total estrogenic bioactivity of serum with very high sensitivity. It has numerous potential applications in pediatric and adult endocrinology. In addition, this assay may help to evaluate excess estrogenic activity related to aromatase overexpression or contamination by environmental chemicals.

Biological Assay↗

PubMed2002

McCune-Albright syndrome: molecular genetics.

McCune-Albright syndrome (MAS) is a rare disorder characterized by the association of precocious puberty (mostly in girls), polyostotic fibrous dysplasia and café-au-lait pigmented skin lesions. In addition to this classical triad, several endocrine disorders, all due to autonomous hormonal hyperproduction, can also be associated, such as pituitary adenomas secreting growth hormone, hyperthyroid goiters, or adrenal hyperplasia. The distribution pattern of skin lesions and the sporadic character of MAS have led to the hypothesis that this syndrome is due to a dominant somatic mutation early in the course of development. Furthermore, the diverse endocrine hyperactivity syndromes observed in MAS have in common the involvement of cells that respond to extracellular signaling by activating the adenyl cyclase system. The identification of somatic mutations of the Gsalpha gene have shown that MAS is due to a post-zygotic activating mutation of the Gsalpha subunit leading to a mosaic distribution of cells bearing constitutively active adenyl cyclase activity. In all patients reported to date, the mutation is a substitution of the arginine residue at position 201 most often into histidine or cysteine. We present here some of the results we have obtained in studying 80 patients presenting one or several signs of MCA for identification of the Arg201 mutation. We used a PCR-based method that allows selective enrichment of mutated DNA. This study, and data in the literature during the last decade, has widened the definition of MAS. Affections as clinically different as somatotropic or thyrotropic adenomas, isolated polyostotic fibrous dysplasia, isolated peripheral precocious puberty and the classic McCune-Albright syndrome all appear to be elements of a wide spectrum of disease based on the same molecular defect. The developmental moment at which the mutation occurs determines both the number of tissues affected and the severity of expression. The application of tools from molecular genetics to the study of this syndrome confirms their essential contribution to a deeper understanding of endocrine pathologies.

Child↗