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PubMed2006

Somatropin therapy for children with prader-willi syndrome : guidelines for use.

Prader-Willi syndrome is a neurogenetic disorder that occurs due to the lack of a paternally expressed gene or genes on chromosome 15q11-q13. Many of the symptoms present in Prader-Willi syndrome are due to a hypothalamic-pituitary dysfunction. The main characteristics are muscular hypotonia, delayed psychomotor development, insatiable appetite resulting in overweight if a diet is not maintained, compromised growth and puberty resulting in a short final height and incomplete sexual development, respiratory disturbances, and dysmorphic features. Individuals with Prader-Willi syndrome have compromised growth and abnormal body composition with increased fat mass, decreased lean body mass, and low bone density, resembling a growth hormone-deficient status. Somatropin treatment has a beneficial effect on growth with increased final height and an improvement in and maintenance of body composition, as well as a beneficial effect on respiratory functions. Before initiating somatropin therapy, weight should be kept at an appropriate level, and polysomnography, as well as an otorhinolaryngologic examination should be performed. During somatropin therapy, carbohydrate metabolism and the development of scoliosis should be monitored, as well as bodyweight.A comprehensive team to manage the various components of medical, psychologic, and sociologic care is required for individuals with Prader-Willi syndrome.

Body Composition↗
PubMed1979

Modifications induced by neonatal steroids in reproductive organs and behavior of male rats.

Male rats injected on Day 3 neonatally with .01, .1, 1, 10, 100, or 1,000 micrograms of estradiol benzoate (EB), 10,000 microgram of testosterone propionate (TP), or sesame oil were subsequently examined for testicular, penile, and accessory organ development. Sexual behavior was evaluated during therapy with fluoxymesterone (FM) and then with TP. Estradiol benzoate in dosages greater than 1.0 micrograms delayed testicular descent, reduced the size and hormone responsiveness of reproductive organs, and decreased sexual behavior in a dose-dependent manner. The 10,000-microgram dosage of neonatal TP delayed testicular descent and reduced sexual behavior to levels near those of the 10--100 micrograms EB groups, but it produced no significant penile or accessory organ changes. Neither reduced peripheral organ development nor inhibited neonatal testicular secretions fully explain reductions in male behavior following large dosages of neonatal TP. Neonatal androgen may reduce the responsiveness of central nervous system neurons governing male sexual behavior after being converted to estrogen or by directly altering steroid receptor systems.

Animals↗
PubMed1988

[Victimologic-oriented study of perpetrator groups--a possibility for synthesis of various crime determinants].

An example of a group of offenders of sexual motivated criminal homicides is the relationship of as well social- sexual developments of offenders, victim properties, preacted interactions between perpetrator and victim as the crime discussed. At this dominate following facts of offender: an undifferentiated aggressive sexuality with a decreasing intelligence, social outstanding and disturbed social adaptability and great portion of sexual preactivities. The childlike victim is the compensation for adult women. The attack takes place with sexual excitation and by the situation opportune facts, an escalation of defence and increasing of excitation of the offender up to the homicide.

Adult↗
PubMed2001

Early puberty and early sexual activity are associated with bulimic-type eating pathology in middle adolescence.

PURPOSE: To examine the associations between early pubertal timing and early advanced sexual development with bulimic-type eating pathology in middle adolescents. METHODS: A total of 19,321 boys and 19,196 girls aged 14-16 years (mean age 15.3 years, standard deviation 0.59) responded to the School Health Promotion Study, a class-room survey among Finnish adolescents about health, health behavior, and school experiences. Bulimic-type eating pathology was assessed with a questionnaire formulated according to the fourth edition of the Diagnostic and Statistical Manual for Mental Disorders IV (DSM-IV) criteria. Pubertal timing was assessed by self-reported age at menarche or oigarche. Statistical methods were used chi-square and logistic regression. RESULTS: Bulimic-type eating pathology among girls was associated with early menarche, early sexual experiences, and increasing age. Among boys, onset of ejaculations at the normative age was protective for bulimic-type eating pathology, and the risk was elevated among very early and late maturers. Early sexual experience was associated with bulimic-type eating pathology. CONCLUSION: To prevent bulimia nervosa and to create opportunities for early intervention, attention should be paid to early maturing girls and off-time maturing boys, as well as those with early onset of sexual activity.

Adolescent↗
PubMed1989

Fetal male masculinization in control and prenatally stressed rats.

The present experiments were designed to test the hypothesis that males in utero masculinize the development of other males. This effect was examined during fetal development in males from control and prenatally stressed rats. A code identified the number of cervical-flanking males between the target male and the cervical end of the uterus. The male parameters morphology (anogenital distance) and body, adrenal, and testis weights were recorded on the eighteenth and twentieth gestational days and categorized by the cervical-flanking male classification. At Day 18, control fetuses with two cervical-flanking males in utero displayed significantly greater anogenital distance values than did males with no cervical-flanking male. At Day 20, control fetuses with two cervical-flanking males had testicular weights significantly greater than those of fetuses with one or zero cervical positioned male. Prenatal stress markedly impaired male fetal development at gestational Days 18 and 20 while suppressing the cervical-flanking male effect. These results confirm and extend previous data that indicate: (a) prenatal stress disrupts normal fetal development, resulting in long-term changes; and (b) androgens via a cervical-flanking blood-flow mechanism influence littermate morphology and sexual development during the prenatal period. Our findings also demonstrate that a general masculinizing effect could not be made across the measured male parameters since the effect of males positioned at the cervical-flanking region in utero appears to be dependent upon maternal sources of variance. Finally, androgens prenatally have an apparent positive interaction with somatic growth.

Adrenocorticotropic Hormone↗
PubMed2006

Identification of the down-regulated genes in a mat1-2-deleted strain of Gibberella zeae, using cDNA subtraction and microarray analysis.

Gibberella zeae (anamorph: Fusarium graminearum), a self-fertile ascomycete, is an important pathogen of cereal crops. Here, we have focused on the genes specifically controlled by the mating type (MAT) locus, a master regulator of sexual developmental process in G. zeae. To identify these genes, we employed suppression subtractive hybridization between a G. zeae wild-type strain Z03643 and the isogenic self-sterile mat1-2 strain T43deltaM2-2. Both reverse Northern and cDNA microarray analyses using 291 subtractive unigenes confirmed that 58.8% (171 genes) were significantly down-regulated in T43deltaM2-2. Among these, 98 could be either manually or automatically annotated based on known functions of their possible homologs. Northern blot analysis revealed that all of the genes examined were differentially regulated by MAT1-2 during sexual development. This study is the first report on the set of genes that are transcriptionally altered by the deletion of MAT1-2 during sexual reproduction in G. zeae.

Blotting, Northern↗
PubMed2000

Endocrine disruptors: present issues, future directions.

A variety of natural products and synthetic chemicals, known collectively as endocrine-disrupting compounds (EDCs), mimic or interfere with the mechanisms that govern vertebrate reproductive development and function. At present, research has focused on (i) the morphological and functional consequences of EDCs; (ii) identifying and determining the relative potencies of synthetic and steroidal compounds that have endocrine-disrupting effects; (iii) the mechanism of action of EDCs at the molecular level; and (iv) the recognition that in "real life," contamination usually reflects mixtures of EDCs. Future research must examine (i) the interactive nature of EDCs, particularly whether the threshold concept as developed in traditional toxicological research applies to these chemicals; (ii) when and how EDCs act at the physiological level, particularly how they may organize the neural substrates of reproductive physiology and behavior; (iii) the various effects these compounds have on different species, individuals, and even tissues; and (iv) how adaptations may evolve in natural populations with continued exposure to EDCs. Several predictions are offered that reflect these new perspectives. Specifically, (i) the threshold assumption will be found not to apply to EDCs because they mimic the actions of endogenous molecules (e.g., estrogen) critical to development; hence, the threshold is automatically exceeded with exposure. (ii) Behavior can compound and magnify the effects of EDCs over successive generations; that is, bioaccumulated EDCs inherited from the mother not only influence the morphological and physiological development of the offspring but also the offsprings' reproductive behavior as adults. This adult behavior, in turn, can have further consequences on the sexual development of their own young. (iii) The sensitivity of a species or an individual to a compound is related to species (individual)-typical concentrations of circulating gonadal steroid hormones. Related to this is the recent finding that alternate forms of the putative receptors are differentially distributed, thereby contributing to the different effects that have been observed. (iv) Except in extraordinary situations, populations often continue to exist in contaminated sites. One possible explanation for this observation that needs to be considered is that animals can rapidly adapt to the nature and level of contamination in their environment. It is unlikely that successive generations coincidentally become insensitive to gonadal steroid hormones fundamentally important as biological regulators of development and reproduction. Rather, adaptive alterations in the genes that encode steroid receptors may occur with chronic exposure to EDCs, allowing the sex hormone receptor to discriminate natural steroids from EDCs.

Adult↗
PubMed2001

SHOX haploinsufficiency and overdosage: impact of gonadal function status.

Since its discovery in 1997, knowledge about the SHOX gene has rapidly increased. In this review, we summarise clinical features and diagnostic and therapeutic implications in SHOX haploinsufficiency and overdosage. SHOX haploinsufficiency usually results in mesomelic short stature and Turner skeletal features, including Madelung deformity with puberty, in subjects with normal gonadal function. Thus, identification of early or mild signs of Madelung deformity is pivotal for the diagnosis, and gonadal suppression therapy may serve to mitigate the clinical features. By contrast, SHOX overdosage usually leads to long limbs and tall stature resulting from continued growth into the late teens in subjects with gonadal dysgenesis. Thus, the combination of tall stature and poor pubertal development is the key to diagnosis, and oestrogen therapy can help the prevention of unfavourably tall stature as well as the induction of sexual development. These findings, in conjunction with skeletal assessment in Turner syndrome and expression analysis during human embryogenesis, imply that SHOX functions as a repressor for growth plate fusion and skeletal maturation in the distal limbs and, thus, counteracts the skeletal maturing effects of oestrogens.

Female↗
PubMed2001

A placebo-controlled, crossover trial of granisetron in SRI-induced sexual dysfunction.

BACKGROUND: Sexual side effects are commonly associated with serotonin reuptake inhibitor (SRI) therapy. The mechanism underlying SRI-induced sexual dysfunction has been hypothesized to be mediated by direct serotonergic effects. Evidence from open-label reports suggests that cyproheptadine, nefazodone, mirtazapine, and mianserin, which block one or more serotonin receptors, may reverse sexual side effects. The current study was a prospective, randomized, crossover trial comparing granisetron, a serotonin-3 antagonist, with placebo in outpatients who developed sexual dysfunction during SRI treatment. METHOD: Thirty-one outpatients who were currently experiencing sexual dysfunction associated with SRIs were randomly assigned to double-blind treatment with granisetron (1-1.5 mg) or placebo for use 1 to 2 hours prior to sexual activity. Patients rated sexual symptoms after each trial using the Sexual Side Effect Scale (SSES). After 4 trials of the medication, patients crossed over to the other treatment for 4 more trials. RESULTS: Twenty patients received at least 1 dose of placebo and granisetron. Analysis by repeated-measures analysis of variance showed no significant effects of granisetron relative to placebo. Significant improvement between baseline and treatment-phase SSES scores was observed for both granisetron (p = .0004) and placebo (p = .0081). The study medication was generally well tolerated. CONCLUSION: The results of this study do not support the efficacy of granisetron (1-2 mg) in the treatment of SRI-associated sexual side effects. A significant placebo response may be associated with the treatment of SRI-induced sexual dysfunction.

Ambulatory Care↗
PubMed1988

Gonadal dimorphism explained as a dosage effect of a locus on the sex chromosomes, the gonad-differentiation locus (GDL).

In human somatic cells bearing two X chromosomes, one X is genetically inactivated throughout most of its length, whereas in cells with one X and one Y both sex chromosomes are active (with the exception of the constitutive heterochromatin of the Y that is inert). The vast base of information concerning normal and abnormal human sexual development that has accumulated since the advent of human cytogenetics 3 decades ago can be integrated by the following hypothesis: Homologous gonad-differentiation loci (GDLs) exist on the X and Y. The GDLs are strictly sex-linked; that is, normally they do not recombine during spermatogenesis, so that considerable divergence in DNA sequence doubtless has occurred between the locus on the X and the locus on the Y. The abundance of their evolutionarily conserved product--a substance still to be identified--determines the path of differentiation that the indifferent gonadal anlage of the early embryo will take: if only one GDL is transcribed, the case when two X chromosomes are present, ovary will develop; if two GDLs are transcribed, the case when a Y is present along with an X, testis will develop. By implication, facultative X inactivation is an integral and essential component of the system adopted in mammalian evolution for accomplishing gonadal--viz., sexual--dimorphism.

Chromosome Mapping↗
PubMed1980

The preoedipal development of the boy.

We have presented an analysis of findings from a ten-year observational study of infants in their second year of life, with a focus on boys. Tracing the sexual development and its relation to development in the object relations and cognitive spheres, we found similarities between boys and girls and sharp differences as well. These latter become evident shortly after the discovery of the anatomical difference. We believe that the differences in reaction to this momentous event account for the greater trouble the girl has in the rapprochement crisis. Our direct observational studies of infants served to clarify many of the preoedipal dynamic currents which in turn affect the form of the oedipal constellation. We have established some sets of conditions which are likely to lead to a negative or positive form or oedipal attachment, and have described the typical and some of the atypical patterns of preoedipal development in both sexes.

Anxiety, Castration↗
PubMed1986

Gonadal development and gonadotrophin secretion in the male vole (Microtus agrestis) after an abrupt change in photoperiod.

Male voles were reared from birth to age 28 days in 6L:18D. Pairs of animals showing similar sexual development were assigned at random to 16L:8D or 6L:18D. Treatments continued for a further 56 days. Increase in the activity of the hypothalamo-hypophysial system occurred within 4 days of exposure to 16L:8D, as shown by significant elevation of plasma LH and FSH. Pituitary LH did not increase until Day 7, and pituitary FSH did not increase until Day 21. After exposure to 16L:8D for 4 days, pituitary FSH was lower than in corresponding animals in 6L:18D. These discrepancies between pituitary and plasma values of gonadotrophins indicate that increase in hormone release occurs before synthesis is fully stimulated. Enhanced output of testicular hormones probably began between Day 7 and Day 14, as indicated by an increase in seminal vesicle weight, yet plasma and pituitary concentrations of LH and FSH remained elevated. This suggests that long photoperiods may cause direct stimulation of the hypothalamo-hypophysial system which increasing values of testicular hormones are initially unable to inhibit. The response of this system in voles to an abrupt change from a non-stimulating to a stimulating photoperiod has a time course resembling that for the Soay ram but appreciably slower than for the Japanese quail.

Animals↗
PubMed1992

Black-white contrasts in insulin levels during pubertal development. The Bogalusa Heart Study.

Three hundred and seventy-seven children and adolescents aged 5-17 yr from the biracial (black-white) community of Bogalusa, Louisiana, were evaluated for Tanner stage of sexual development, plasma glucose, and insulin levels during an oral glucose tolerance test. Children of the two races were of similar age, weight, and height at each Tanner stage. Overall insulin response was compared by measuring the area under the insulin curve from the glucose tolerance test. Blacks, especially black females, had significantly higher insulin responses than their white counterparts. The insulin-glucose ratio at the initial t = 0 min baseline did not vary with race or sex throughout the Tanner stages. However, the 30 min postglucose data revealed clear differences between the races with blacks showing a higher insulin-glucose ratio. Ratios increased throughout puberty for both blacks and whites, boys and girls. The trends of racial contrasts seemed to be discernible even at the earliest stage of development. It is concluded that there is a clear difference between blacks and whites in insulin response to a glucose load early in childhood. These findings lead to the hypothesis that the greater prevalence of non-insulin-dependent diabetes mellitus seen in adult blacks, especially females, may be an expression of a difference in insulin secretion and related insulin resistance in early childhood.

Adolescent↗
PubMed1998

The mating type locus of Neurospora crassa: identification of an adjacent gene and characterization of transcripts surrounding the idiomorphs.

Complexity in and around the A and a mating type idiomorphs in Neurospora crassa was examined. Six sets of transcripts surrounding the idiomorphs were identified by Northern analysis. Several different patterns of regulation were observed. The two pairs of transcripts closest to the centromere-proximal idiomorph flanks (variable regions) exhibited mating type-specific size differences. DNA sequence was obtained for the region surrounding the four transcripts which showed mating type-specific size and expression. One of these pairs encoded amino acid sequences highly similar to a domain present in the plasma membrane ATPase. A mutant allele of one of these genes was induced by repeat-induced point mutation (RIP), which resulted in altered perithecial development and the elimination of ascospore production. These transcripts comprise a cluster of genes which may be involved in the control of mating and sexual development in N. crassa.

Centromere↗
PubMed2001

Molecular genetic dissection of the sex-specific and vital functions of the Drosophila melanogaster sex determination gene fruitless.

A multibranched hierarchy of regulatory genes controls all aspects of somatic sexual development in Drosophila melanogaster. One branch of this hierarchy is headed by the fruitless (fru) gene and functions in the central nervous system, where it is necessary for male courtship behavior as well as the differentiation of a male-specific abdominal structure, the muscle of Lawrence (MOL). A preliminary investigation of several of the mutations described here showed that the fru gene also has a sex-nonspecific vital function. The fru gene produces a complex set of transcripts through the use of four promoters and alternative splicing. Only the primary transcripts produced from the most distal (P1) promoter are sex-specifically spliced under direction of the sex-determination hierarchy. We have analyzed eight new fru mutations, created by X-ray mutagenesis and P-element excision, to try to gain insight into the relationship of specific transcript classes to specific fru functions. Males that lack the P1-derived fru transcripts show a complete absence of sexual behavior, but no other defects besides the loss of the MOL. Both males and females that have reduced levels of transcripts from the P3 promoter develop into adults but frequently die after failing to eclose. Analysis of the morphology and behavior of adult escapers showed that P3-encoded functions are required for the proper differentiation and eversion of imaginal discs. Furthermore, the reduction in the size of the neuromuscular junctions on abdominal muscles in these animals suggests that one of fru's sex-nonspecific functions involves general aspects of neuronal differentiation. In mutants that lack all fru transcripts as well as a small number of adjacent genes, animals die at an early pupal stage, indicating that fru's function is required only during late development. Thus, fru functions both in the sex-determination regulatory hierarchy to control male sexual behavior through sex-specific transcripts and sex-nonspecifically to control the development of imaginal discs and motorneuronal synapses during adult development through sex-nonspecific transcript classes.

Alleles↗
PubMed2002

Interaction between mating-type proteins from the homothallic fungus Sordaria macrospora.

Mating-type genes control sexual development in ascomycetes. Little is known about their function in homothallic species, which are self-fertile and do not require a mating partner for sexual reproduction. The function of mating-type genes in the homothallic fungus Sordaria macrospora was assayed using a yeast system in order to find properties typical of eukaryotic transcription factors. We were able to demonstrate that the mating-type proteins SMTA-1 and SMTa-1 have domains capable of activating transcription of yeast reporter genes. Two-hybrid analysis for heterodimerization and homodimerization revealed the ability of SMTA-1 to interact with SMTa-1 and vice versa. These two proteins are encoded by different mating types in the related heterothallic species Neurospora crassa. The interaction between SMTA-1 and SMTa-1 was defined by experiments with truncated versions of SMTA-1 and in vitro by means of protein cross-linking. Moreover, we gained evidence for homodimerization of SMTA-1. Possible functions of mating-type proteins in the homothallic ascomycete S. macrospora are discussed.

Amino Acid Sequence↗
PubMed1984

Influence of photoperiodism on testicular function and sebaceous glands in Syrian hamster.

The photoperiod (i.e., the daylight fraction of the 24-h day and its seasonal changes) influences the annual cycle of many mammalian species. Especially the Syrian hamster (Mesocricetus auratus), which is an appropriate animal model to investigate the sebaceous gland activity, shows a strong photoperiodism controlling the sexual development as well as the function of androgen-controlled organs such as sebaceous glands. Short photoperiods with accompanying long dark periods lead to a sexual regression while long photoperiods stimulate the recrudescence. In light-physiologic studies Syrian hamsters were exposed to different light schedules. The daily light exposure was increased from 8 to 12, 13, 14, and 16 h. Sebaceous gland areas, weight of testes and accessory glands, tubular areas, and plasma levels of testosterone were determined. Syrian hamsters are sexually stimulated at a daily light exposure of 14 h. Below this light threshold the sexual regression begins. At a light schedule of 8 h the testes shrink, plasma testosterone levels and sebaceous gland areas show a significant reduction ("photoperiodic castration"). Therefore, in experiments of androgen-controlled organs of the Syrian hamster a minimum daily light period of 14 or 16 h is necessary for a sufficient testicular function and therefore for an effective stimulation of the sebaceous gland activity. Control animals of the same age and the same light schedule should be required to avoid pitfalls of photoperiodic effects.

Animals↗