SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Sex differentiation is determined by a cascade of events proceeding from chromosomal sex to the completion of sexual maturation at puberty. Many factors involved in this cascade have been identified. Here we focus on DAX-1, androgen receptor and cytochrome P450c17, and discuss their functions in sex differentiation. We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism using PCR amplification of genomic DNA and complete exonic sequencing, and established that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene. Androgen insensitivity syndrome (AIS) is a good model to clarify the relationship between the structure and function of androgen receptor, the androgen receptor gene mutation and clinical phenotype. We analyzed 15 cases of AIS and demonstrate the structural and functional relationships of the androgen receptor. We have sequenced the CYP17 (P450c17) gene in DNA from several patients with 17 alpha-hydroxylase deficiency, reconstructed the mutations in a human P450c17 cDNA and expressed the mutant P450c17 in COSl cells to characterize the kinetic properties of 17 alpha-hydroxylase and 17,20-lyase activities. The molecular bases of cases clinically reported as 17 alpha-hydroxylase deficiency have turned out to be complete or partial combined deficiencies of 17 alpha-hydroxylase/17,20-lyase.
The mechanisms for sex differentiation and the genes on the sex chromosomes are varied among different species. For human, SRY is the only testis-determining factor on the Y chromosome and triggers the cascade for male sex-determination. However, even if normal SRY exists, the haploinsufficienty of SOX9 or KTS+ splicing form of WT-1 can cause male-to-female sex reversal. Furthermore, the duplication of the partial region on the X chromosome including DAX-1 gene can also cause male-to-female sex reversal. The sex-determining system seems to be sensitive for the gene dosage or the gene expression level.
Explore the source record for details and available documents.
Sex determination in mammals proceeds like a cascade from the level of the sex chromosomes to the gonads, to the genital ducts, and finally to the expression of the male or female phenotype. At the level of the genital ducts male sex organs are induced by testosterone. Its action depends on an intact cytoplasmic androgen receptor protein. The testicular feminization mutation (tfm) leads to loss of hormone binding capacity. Individuals with testes but female external phenotype develop. In the mouse the interaction of androgen insensitive Tfm cells with normal cells can be studied in mosaic individuals composed of both cell types, and in organ culture by recombination of Tfm and normal tissues. The experiments show that under the action of testosterone the normal cells express male differentiated cellular functions, whereas the Tfm cells differentiate in female direction. In respect to proliferation and expression of male or female organ structures, however, both cell types communicate via local factors. Thus, instead of irregular malformations intersex organs develop.
This study investigated the possibility that the histological process of gonadal sex differentiation in pejerrey (Odontesthes bonariensis), a fish with marked temperature-dependent sex determination (TSD), occurs through a predictable gradient of differentiation as opposed to simultaneous or random differentiation throughout the gonad. For this purpose, fish reared at 17 degrees, 24 degrees, and 29 degrees C from hatching were sampled weekly for 11 weeks, fixed, and prepared for histological observation of serial cross-sections of the gonads. The thermal manipulation and sampling procedure ensured the availability of males and females at various degrees of gonadal sex differentiation. The location of the differentiated area(s) was estimated in the right and left gonads of 17 females and 14 males selected among the available specimens so as to represent increasing degrees of differentiation. The analysis revealed that sex differentiation followed a gradient from the anterior to posterior areas of the gonads regardless of sex. Furthermore, plotting of the degree of sex differentiation in the right gonad as a function of the degree of differentiation of the left gonad clearly showed that sex differentiation only begins in the right gonad when 10-30% of the length of the left gonad has already differentiated. The mean rostral edge of the differentiated areas in females was 9% and 10.8% for the left and right gonads, respectively, while for males these values were 7.3% and 7.0%, respectively. Thus, it was established that ovarian and testicular differentiation in pejerrey follow both a cephalocaudal and a left-to-right gradient. Possible explanations for this gradient and its relevance for TSD in pejerrey, that is, as a mechanism to prevent discrepant differentiation of male and female features within the same gonad, are discussed.
Explore the source record for details and available documents.
Mammalian sex differentiation involves the action of a cascade of genes. Discovery of the sex-determining region of the Y chromosome (SRY) marked the beginning of the delineation of the genes in the cascade. Studies of the genetics of mammalian sex reversal and the embryogenesis of the mice are essential in this endeavor. A number of genes involved in the pathway have been identified and all except one of these genes have a putative role in male sex differentiation. Besides SRY being the master switch in male sex differentiation the hierarchical relationship of the genes identified are far from being understood. Similarly, our knowledge of the genetic regulation of female sex differentiation is minimal. Differential screening and gene expression profiling bring a new dimension to the pursuit with the identification of a number of genes previously unknown to be involved in sex differentiation. Wider application of functional genomic techniques and introduction of proteomic analyses are expected to shed light to our understanding of this complicated developmental process.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Mammalian sex differentiation is a hormone-dependent process in the male following the determination of a testis from the indifferent gonad through a cascade of genetic events. Female sex differentiation is not dependent on ovarian hormones, yet there is evidence that members of the Wnt family of developmental signaling molecules play a role in Müllerian duct development and in suppressing Leydig cell differentiation in the ovary. The testis induces male sex differentiation (including testis descent) through a time-dependent production of optimal concentrations of anti-Müllerian hormone, insulin-like factor(s) and androgens. Observations in several human syndromes of disordered fetal sex development corroborate findings in murine embryo studies, although there are exceptions in some gene knockout models. The ubiquitously expressed AR interacts in a ligand-dependent manner with coregulators to control the expression of androgen-responsive genes. Preliminary studies suggest the possibility of hormone resistance syndromes associated with coregulator dysfunction. Polymorphic variants in genes controlling androgen synthesis and action may modulate androgenic effects on sex differentiation.
Sex differentials in life expectancy at birth in Japan are analyzed for the period 1920 to 1990. The results show that there was a general increase in differences in mortality by sex over time. "The sex differential in age-specific death rate in 0-4 year age group (particularly age 0) explained most of the sex differential in life expectancy at birth before 1947. After 1950, the age group of 60-79 played a major role in the sex differential in life expectancy at birth. It is noteworthy that female mortality exceeded male mortality in age groups of 2-41 before 1930. Consequently, excess of female mortality reduced the sex differential in life expectancy at birth at that period. As for the sex differential in mortality rates by causes of death, tuberculosis, pregnancy and childbirth related disease exerted a great influence...before 1940. Recently, malignant neoplasms, heart diseases, cerebrovascular diseases, and accidents [have] become leading contributors to the sex differentials in life expectancy at birth." (SUMMARY IN ENG)
Sex-differentiation in mammals initiates at mid-gestation when the differentiation of Sertoli cells is triggered by the expression of the testis-determining gene, Sry. However, little is known about the succeeding germ-soma interaction that directs the sex-differentiation of germ cells. We carried out subtraction and differential screening between male and female gonads at 13.5 dpc (days post coitum). A novel cystatin-related gene was identified and named cresp (cystatin-related expressed in Sertoli and spermatogonia), and has recently been reported independently under the name testatin (Töhönen et al., 1998). The presumed amino acid sequence of testatin/cresp showed considerable homology to the cystatin family, but it lacked a few critical amino acid residues for the cysteine-protease inhibitory activity. A 0.7 kb RNA was detected by northern blotting specifically in the fetal and adult testes from 11.5 dpc and expression increased between 11.5 dpc and 12.5 dpc. Using RT-PCR analysis, the testatin/cresp mRNA was first detectable at 9.5 dpc in both male and female embryos but it was maintained only in the male. In females, the expression became weaker at 11.5 dpc and was undetectable after 12.0 dpc. In situ hybridization and immunohistochemical analyses, as well as single cell RT-PCR analysis, showed that the testatin/cresp mRNA was localized specifically in both the (pro)spermatogonia and Sertoli cells in the testis from 12.5 dpc to adult. Thus, expression of the testatin/cresp gene is upregulated in male gonads but downregulated in females immediately after the initiation of sex-differentiation, suggesting roles in the early developmental cascade of testis such as the germ-soma interaction.
Androgen and estrogen metabolism were examined in the period of steroid sensitivity during sex differentiation in mono-sex populations of Oreochromis niloticus. Fry (XX, XY, and YY genotypes) were maintained at 28 degrees and were sampled at 8, 10, 11, and 13 days postfertilization. Subsamples (n = 2-4) of pooled fry from each maternally distinct family were homogenized and incubated with either [(3)H]androstenedione or [(3)H]estradiol. Metabolites present in organic extracts were identified by thin-layer chromatography, microchemical reactions, and recrystallization to constant specific activity. Androstenedione was metabolized into at least seven readily identifiable compounds by all genotypes. In the XY genotype, 5beta-androstane-3alpha,17beta-diol synthesis decreased rapidly from 8 to 13 days postfertilization, with a concomitant increase in testosterone synthesis. Testosterone synthesis did not increase in the XX genotype. Testosterone synthesis in the YY genotype was intermediate to that of the XY and XX genotypes. Estrogens were not synthesized by any genotype. We hypothesize that 5beta-reduction (or further hydroxylation) is a mechanism important in regulating testosterone production and subsequent sex differentiation. Results of incubations with estradiol show an age-dependent increase in metabolism which did not vary among genotypes. Metabolites synthesized included estrone and up to five unidentified compounds.
This study applies two methodologies to Mauritian life tables and cause-of-death data: (1) the decomposition of sex differentials in life expectancy using Arriaga's approach and (2) the estimation of the effect of marginal reduction in deaths from infectious and parasitic diseases on life expectancy using Keyfitz's methodology on cause-specific entropy and that of Nanjo. The findings in this paper support earlier findings about the importance of the period 1969-1976 in the mortality transition in Mauritius, a period in which sex differentials in life expectancies reached a peak level. The results suggest that the driving force behind those sex differentials in life expectancy was the sex differential in mortality in infectious and parasitic diseases, first among the young (ages below 10 years) and second among the older population (ages above 50 years). If the decline in mortality due to infectious and parasitic diseases was differentially greater in the older ages compared to the younger ages, that difference would have gone a long way toward reducing the magnitude of the historic peak sex differential in life expectancy achieved in 1976.
Explore the source record for details and available documents.