2
AU - Wiener JS
AU - Marcelli M
AU - Lamb DJ
TI - Molecular determinants of sexual differentiation.
AB - The processes of sexual differentiation have been greatly clarified by molecular biologic discoveries over the past five years. Gonadal differentiation into a testis or ovaries is controlled by a multitude of genes beginning with SRY which is believed to represent the testis determining factor. Other genes involved include SF-1, WT-1, DAX-1, and SOX9. The fully developed testis produces Mullerian inhibiting substance and testosterone to create the male phenotype; the female phenotype develops in their absence. This hormonally-driven process also requires additional factors and appropriate receptors. Errors in this pathway may be manifested clinically as intersex disorders, and the study of these disorders has helped to further elucidate the molecular mechanisms of sexual differentiation.
MH - Sex Differentiation|*GE
AD - Department of Urology
AD - Baylor College of Medicine
AD - Houston
AD - Texas
AD - USA.
SO - World J Urol 1996; 14(5):278-94
DP - 1996
TA - World J Urol
PG - 278-94
IP - 5 VI - 14
UI - 97069340

3
AU - Schlaepfer TE
AU - Harris GJ
AU - Tien AY
AU - Peng L
AU - Lee S
AU - Pearlson GD
TI - Structural differences in the cerebral cortex of healthy female and male subjects: a magnetic resonance imaging study.
AB - There are both reproductive and nonreproductive behavioral differences between men and women. Brain regions involved in determining sexual behavior have been reported to differ between the sexes. Nonreproductive, cognitive functional differences between sexes might be reflected in higher-order cortical structural dimorphisms, which have not previously been studied. We hypothesized that cortical regions involved in verbal behavior (which is sexually dimorphic) would differ between sexes. Using magnetic resonance imaging, we assessed gray matter volumes in several cortical regions in 17 women and 43 men. Women had 23.2% (dorsolateral prefrontal cortex) and 12.8% (superior temporal gyrus) greater gray matter percentages (corrected for overall brain size and age) than men in a language-related cortical region, but not in a more visuospatially related cortical region. These data seem to establish sexually dimorphic structural differences in the cerebral cortex, consistent with prior cerebral blood flow reports. MH - Cerebral Cortex|*AH MH - Dominance, Cerebral|*PH MH - Magnetic Resonance Imaging|* MH - Sex Characteristics|* AD - Department of Psychiatry AD - Johns Hopkins University AD - Baltimore AD - MD 21287-7362 AD - USA. SO - Psychiatry Res 1995 Sep 29; 61(3):129-35 DP - 1995 Sep 29 TA - Psychiatry Res PG - 129-35 IP - 3 VI - 61 UI - 96117674

4 AU - Tsutsumi O
AU - Iida T
AU - Nakahori Y
AU - Taketani Y
TI - Analysis of the testis-determining gene SRY in patients with XY gonadal dysgenesis.
AB - The sex-determining region of the Y chromosome (SRY) encodes a gene that has many of the properties expected to the testis-determining factor. XY gonadal dysgenesis is characterized by streak gonads in phenotypic females who lack the somatic abnormalities and short stature associated with Turner's syndrome. We have examined four patients with XY gonadal dysgenesis for the presence and absence of SRY and the DNA sequence of the gene. The results showing that one was negative for SRY and another had a mutation within the gene have confirmed the etiological role of SRY in XY gonadal dysgenesis. However, the other two patients with short stature had apparently normal SRY. DNA sequencing of the SRY gene showed 100% nucleotide sequence identity with the reported cloned sequence. Sex reversal in two of the present cases may be due to mutation at a locus other than SRY in the sex-determining pathway, a gene potentially involved in the determination of human sexual constitution.
MH - DNA-Binding Proteins|*GE
MH - Gonadal Dysgenesis|*GE/SU
MH - Y Chromosome|*GE
AD - Department of Obstetrics and Gynecology
AD - Faculty of Medicine
AD - University of Tokyo AD - Japan.
SO - Horm Res 1996; 46 Suppl 1():6-10
DP - 1996
TA - Horm Res
PG - 6-10
VI - 46 Suppl 1
UI - 97018125

5
AU - Crews D
AU - Bergeron JM
AU - McLachlan JA
TI - The role of estrogen in turtle sex determination and the effect of PCBs.
AB - In the current model of vertebrate sex determination and sexual differentiation, gonadal sex is fixed at fertilization by specific chromosomes, a process known as genotypic sex determination (GSD). Only after the gonad is formed do hormones begin to exert an influence that modifies specific structures that eventually will differ the sexes. Many egg-laying reptiles do not exhibit GSD but rather depend on the temperature of the incubating egg to determine the gonadal sex of the offspring, a process termed temperature-dependent sex determination (TSD). Research on TSD indicates that sex determination in these species is fundamentally different in at least one way. Gonadal sex is not irrevocably set by the genetic composition inherited at fertilization but depends ultimately on which genes encoding for steroidogenic enzymes and hormone receptors are activated during the midtrimester of embryonic development by temperature. Incubation temperature modifies the activity as well as the temporal and spatial sequence of enzymes and hormone receptors such that sex-specific hormone milieus, created in the urogenital system of the developing embryo, determine gonad type. Estrogen is the physiologic equivalent of incubation temperature and the proximate cue that initiates female sex determination. There is increasing evidence that some polychlorinated biphenyl (PCB) compounds are capable of disrupting reproductive and endocrine function in fish, birds, and mammals, including humans. Reproductive disorders resulting from exposure to these xenobiotic compounds may include reductions in fertility, hatch rate in fish and birds, and viability of offspring, as well as alterations in hormone levels or adult sexual behaviors, all of which have further implications, particularly in wildlife population dynamics. Research on the mechanism through which these compounds may be acting to alter reproductive function indicates estrogenic activity, by which the compounds may be altering sexual differentiation. In TSD turtles, the estrogenic effect of some PCBs reverses gonadal sex in individuals incubating at an otherwise male-producing temperature. Furthermore, certain PCBs are synergistic in their effect at very low concentrations.
MH - Estrogens|*PH
MH - Polychlorinated Biphenyls|*TO
MH - Sex Determination|*
MH - Turtles|*PH
AD - Institute of Reproductive Biology
AD - University of Texas at Austin 78712
AD - USA. crews@bull.zo.utexas.edu
SO - Environ Health Perspect 1995 Oct; 103 Suppl 7():73-7 DP - 1995 Oct
TA - Environ Health Perspect
PG - 73-7
VI - 103 Suppl 7
UI - 96163758

6
AU - Ito H
AU - Fujitani K
AU - Usui K
AU - Shimizu-Nishikawa K
AU - Tanaka S
AU - Yamamoto D
TI - Sexual orientation in Drosophila is altered by the satori mutation in the sex-determination gene fruitless that encodes a zinc finger protein with a BTB domain. AB - We have isolated a new Drosophila mutant, satori (sat), the males of which do not court or copulate with female flies. The sat mutation comaps with fruitless (fru) at 91B and does not rescue the bisexual phenotype of fru, indicating that sat is allelic to fru (fru(sat)). The fru(sat) adult males lack a male-specific muscle, the muscle of Lawrence, as do adult males with other fru alleles. Molecular cloning and analyses of the genomic and complementary DNAs indicated that transcription of the fru locus yields several different transcripts. The sequence of fru cDNA clones revealed a long open reading frame that potentially encodes a putative transcription regulator with a BTB domain and two zinc finger motifs. In the 5' noncoding region, three putative transformer binding sites were identified in the female transcript but not in male transcripts. The fru gene is expressed in a population of brain cells, including those in the antennal lobe, that have been suggested to be involved in determination of male sexual orientation. We suggest that fru functions downstream of tra in the sex-determination cascade in some neural cells and that inappropriate sexual development of these cells in the fru mutants results in altered sexual orientation of the fly.
MH - Drosophila|*GE/PH
MH - Sex Behavior, Animal|*PH
MH - Zinc Fingers|*GE
AD - Yamamoto Behavior Genes Project
AD - Exploratory Research for Advanced Technology (ERATO) AD - Research Development Corporation of Japan AD - Tokyo AD - Japan.
SO - Proc Natl Acad Sci U S A 1996 Sep 3; 93(18):9687-92
DP - 1996 Sep 3
TA - Proc Natl Acad Sci U S A
PG - 9687-92 IP - 18 VI - 93
UI - 96382528
GENBANK/D84437
GENBANK/D84438

7
AU - Zamboni G
AU - Antoniazzi F
AU - Tatao L
TI - [Sex differentiation and its anomalies]
AB - Sex determination and differentiation is a sequential process that involves genetic, gonadal, phenotypic and psychological sex. Sex determination is primarily testis determination. The primary event is differentiation of the gonad; all subsequent sexual differentiation is hormonally controlled. The Authors present a classification of abnormal sexual development and consider the errors of primary sex differentiation (anomalies of sex chromosomes and of gonadogenesis) and the errors of sexual differentiation (inadequate masculinization of genetic male and virilization of genetic female). At the end the clinical approach to disorders of sexual differentiation is briefly considered. MH - Sex Differentiation|* MH - Sex Differentiation Disorders|*CL/DI/GE AD - Clinica Pediatrica AD - UniversitÄa di Verona AD - Italia.
SO - Pediatr Med Chir 1996 Jan-Feb; 18(1):3-12
DP - 1996 Jan-Feb
TA - Pediatr Med Chir
PG - 3-12
IP - 1
VI - 18
UI - 96265859

8
AU - Sultan C AU - Lumbroso S AU - Poujol N AU - Boudon C AU - Georget V AU - TÆerouanne B AU - Belon C AU - Lobaccaro JM TI - [Genetics and endocrinology of male sex differentiation: application to molecular study of male pseudohermaphro ditism] AB - The various processes involved in sexual differentiation have been considerably clarified over the last few years through advances in biochemistry and molecular genetics. The cloning of the gene responsible for testicular determination SRY, of the anti-MÂullerian hormone and anti-MÂullerian hormone receptor genes, of the several steroidogenic enzymes genes, of the 5 alpha-reductase type 2 gene and of the androgen receptor gene has permitted to elucidate the molecular defects causing abnormal sexual differentiation. These data have brought a substantial impact on the understanding of human male sexual differentiation and its main diso rders. MH - Pseudohermaphroditism|*GE/*ME MH - Sex Differentiation|* AD - INSERM U439 AD - HÈopital Lapeyronie AD - Montpellier AD - France. SO - C R Seances Soc Biol Fil 1995; 189(5):713-40 DP - 1995 TA - C R Seances Soc Biol Fil PG - 713-40 IP - 5 VI - 189 UI - 96263425

9
AU - Davis EC
AU - Popper P
AU - Gorski RA
TI - The role of apoptosis in sexual differentiation of the rat sexually dimorphic nucleus of the preoptic area.
AB - The sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat hypothalamus is larger in volume in males than in females due to a larger number of cells in the nucleus. Although the SDN-POA, and its development, have been extensively studied, the actual mechanism of its sexual differentiation has not been established. The results of previous studies have not supported a role for gonadal steroids in the regulation of neurogenesis or the determination of the migratory pathway perinatally. In this study, the role of cell death in the development of the sexual dimorphism in the SDN-POA was investigated using in situ end-labeling to visualize fragmented DNA in apoptotic cells. In the experiments described here, the incidence of apoptosis was determined in part of the SDN-POA, the central division of the medial preoptic nucleus (MPNc), over the first 13 days postnatally in male and female rats. There was a sex difference in the incidence of apoptosis in the MPNc between postnatal days 7 and 10; the incidence was higher in females. The role of testosterone (T) in regulating the incidence of apoptosis in the developing MPNc was examined in neonatally castrated males following T or vehicle injection. Testosterone had a profound inhibitory effect on the incidence of apoptosis between days 6 and 10. In a control region within the lateral preoptic area, there was no sex difference in the incidence of apoptosis, nor was there an effect of T. Thus, the data indicate that the regulation of apoptosis by T is one mechanism involved in the sexual differentiation of the SDN-POA.
MH - Animals, Newborn|*GD MH - Apoptosis|DE/*PH MH - Preoptic Area|*CY/*PH MH - Sex Characteristics|* MH - Sex Differentiation|*PH AD - University of California AD - Department of Neurobiology AD - Los Angeles 90095-1763 AD - USA.
SO - Brain Res 1996 Sep 23; 734(1-2):10-8
DP - 1996 Sep 23
TA - Brain Res
PG - 10-8
IP - 1-2
VI - 734
UI - 97052168