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PubMed1995

The social effects in adult life of chronic physical illness since childhood.

UNLABELLED: An unselected group of 487 (222 females, 265 males) patients with juvenile onset chronic physical disorders was studied at the age of 19-25 years for their social outcome and compared with an age-matched group of 202 physically healthy controls. The interview covered both comprehensive and vocational schooling, data on their employment status, relationship to parents and sexual development in detail. The overall social maturation index showed poor social maturation in patients more often than in the controls. At the time of the study 23% of the patients and 11% of the controls had no vocational education or were not on their way to gaining it. Excluding those with a disability pension (10%), working experience, employment status and unemployment were fairly similar in both groups. Sexual development was delayed more often in the patients than in the controls and the patients were significantly more often unmarried and living in the same household as their parents. However, social and psychological factors accumulating in excess in the patient group were observed more significant than the physical disease to the delayed social maturation. CONCLUSION: Among patients with chronic physical disorders there is a minor group with delayed social maturation. Those at risk can easily be recognized even before adolescence in order to offer them and their parents support to achieve reasonable social development in early adulthood.

Adolescent↗
PubMed2004

Direct activation of fission yeast adenylyl cyclase by heterotrimeric G protein gpa2.

Genetic studies on Schizosaccharomyces pombe adenylyl cyclase (cyr1) have shown that its activity is positively regulated by a heterotrimetric G protein a subunit gpa2 and that the resulting increase in intracellular cAMP concentration causes inhibition of sexual development including mating and meiosis. However, molecular mechanism underlying this gpa2-dependent regulation of cyr1 remains to be clarified. Here, we show that gpa2 exhibits a direct and GTP-dependent binding to the Ras-associating domain (RAD) of cyr1, which is identified by a computer algorithm-based search of the cyr1 amino acid sequence. Overexpression of this RAD results in acceleration of the sexual development of fission yeast cells presumably by competitive sequestration of gpa2. Furthermore, cyr1 is activated in vitro by the addition of purified gpa2, which is converted to the active state by treatment with AlF4-. These results indicate a crucial role of the RAD as a direct binding site of gpa2 in activation of cyr1. Thus, RADs, which have been defined as a conserved motif shared among the Ras-family small G protein-associating domains, are for the first time shown to exhibit a functional association with a member of the heterotrimeric G proteins.

Adenylyl Cyclases↗
PubMed1992

Effects of sex steroids on the development of sexual dimorphism in mouse innominate bone.

The sexual dimorphism of the innominate bone was examined in 14 strains of mice. In female mice of all strains, the pubis was significantly longer and thinner than that in the strain-matched males. In 13 of 14 strains, the ischium in the male was longer and thicker than in the female. In the testicular-feminized male (Tfm) mouse, the ischium was longer and thinner than that in the wild-type male, resembling that of the wild-type female. The pubis of the Tfm mouse was longer than in the wild-type males. The pubis width in the Tfm mouse was between those of the wild-type male and female. Gonadectomy at ages of 5, 10, 20, 30, and 60 days in both sexes showed that the ischium develops as the female type when sex hormones are absent. In contrast, postnatal testicular androgen induces the male-type ischium. Gonadectomy at 60 days had a slight effect on the pubis, indicating that sexual dimorphism of the pubis was determined before 60 days of age. Estrogen receptors (ER) were immunohistochemically demonstrated in bone cells of 0- to 60-day-old mice. ER was found exclusively in the periosteum of the pubis at the day of birth; however, it appeared in bone cells of all parts of pelvis at 10-60 days. These results indicate that sexual dimorphism of the pubis is consistent for the 14 mouse strains examined, and that the shape of the pubis is determined by sex steroids before 60 days of age. Since ER exist in the bone cells, morphogenesis of the pelvis may be regulated by these sex steroids.

Animals↗
PubMed1985

Effects of prenatal exposure to morphine on the development of sexual behavior in rats.

Females exposed to morphine sulfate in utero (5-10 mg/kg twice a day on days 11-18 of gestation) displayed precocious vaginal opening and had increased body weight from the 8th week after weaning. In addition, there was a substantial inhibition in adult feminine sexual behavior. Male rats that received either morphine or saline prenatally did not show any body weight differences, and most of the measures of masculine sexual behavior did not differ between the two groups. However, the male rats exposed to morphine had a significantly shorter post-ejaculatory intromission latency than the saline controls. Examination of cytosol estrogen receptor levels in the hypothalamus-preoptic area (HPOA) of both saline and morphine sulfate-treated female rats revealed essentially identical patterns of depletion and replenishment. Additionally, estrogen treatment was equally effective at inducing HPOA progestin receptor synthesis in both groups. These results show that prenatal morphine treatment at the times and dose level administered disrupts the development of reproductive function in females but has only minor effects on male reproductive function.

Animals↗
PubMed1975

Typical Turner's syndrome with 45 XO karyotype and normal menstruation. Cytogenetic and histological findings.

The clinical, laboratory, histological and cytogenic findings in a patient with Turner's syndrome with normal menstruation are presented. Although the phenotype and karyotype were those of Turner's syndrome, normal sexual development and periods occurred at puberty. The endocrine studies revealed onyl a mild diabetic oral glucose tolerance test. At laparotomy, normal uterus, Fallopian tubes and ovaries were seen. Histological examination of the ovaries showed several primordial follicles and a follicle cyst. Tissue cultures of lymphocytes, skin fibroblasts and ovary revealed a single line of cells with the 45 XO karyotype. Although 25 cases of Turner's syndrome with normal sexual development have been reported, most of them were mosaics and only a small number showed the pure 45 XO karyotype.

Adolescent↗
PubMed1991

The nutritional consequences of gastrointestinal disease in adolescence.

The growth spurt of adolescence, during which body weight nearly doubles and height increases by 16%, demands an increased delivery of nutrients by the gastrointestinal tract. Chronic disorders of digestion and absorption at this age, therefore have a potentially profound effect upon growth, skeletal maturation and sexual development. Moreover, the emotional climate of adolescence, which requires affiliation with peer groups, and a distancing from authority figures such as doctors and parents, is often associated with a deterioration in drug and dietary compliance and with erratic clinic attendance. Nutritional problems in adolescent patients with Crohn's disease, cystic fibrosis and coeliac disease are the most common. About one third of adolescents with Crohn's disease experience growth failure and delayed sexual development, probably as a consequence of long-term undernutrition. There is a strong argument for the care of these patients being in the hands of paediatric gastroenterologists. Enteral nutrition, often administered overnight, is successful in inducing catch-up growth, and reducing steroid dosage, although resection of diseased gut is often followed by good growth, and surgery should not be overlooked. Cystic fibrosis in adolescence is commonly complicated by protein-energy malnutrition. Pathogenesis includes anorexia, maldigestion and an increase in resting energy expenditure. Malnutrition has been treated by a number of enteral regimens. In general, there is no place for repeated, short-term interventions of less than 6 months. Long-term studies have all shown good nutritional repletion and growth, but results with respect to improved respiratory function are conflicting. More prospective control trials are needed before the precise indications for enteral nutrition in cystic fibrosis can be accurately defined. Once started it is difficult to stop, although preoperative treatment of patients awaiting heart-lung transplantation seems entirely appropriate. The major problem in the management of coeliac disease in adolescence is dietary compliance. Even those patients who claim to have good dietary compliance often have jejunal biopsy evidence of gluten ingestion and tend to be underweight. This is particularly worrying, as after 5 years adherence to a gluten free diet, the increased risk of gastrointestinal malignancy appears to return to normal.

Adolescent↗
PubMed2002

Mating-type locus of Cryptococcus neoformans: a step in the evolution of sex chromosomes.

The sexual development and virulence of the fungal pathogen Cryptococcus neoformans is controlled by a bipolar mating system determined by a single locus that exists in two alleles, alpha and a. The alpha and a mating-type alleles from two divergent varieties were cloned and sequenced. The C. neoformans mating-type locus is unique, spans >100 kb, and contains more than 20 genes. MAT-encoded products include homologs of regulators of sexual development in other fungi, pheromone and pheromone receptors, divergent components of a MAP kinase cascade, and other proteins with no obvious function in mating. The alpha and a alleles of the mating-type locus have extensively rearranged during evolution and strain divergence but are stable during genetic crosses and in the population. The C. neoformans mating-type locus is strikingly different from the other known fungal mating-type loci, sharing features with the self-incompatibility systems and sex chromosomes of algae, plants, and animals. Our study establishes a new paradigm for mating-type loci in fungi with implications for the evolution of cell identity and self/nonself recognition.

Alleles↗
PubMed1985

Influence of undernutrition during gestation and suckling on development and sexual maturity in the rat.

The effects of undernourishment during gestation and suckling on rats subsequently fed ad libitum for 4 mo after weaning are explored. We measured the following: weight at birth and over a 5-mo period; sexual behavior of adult males; curiosity; basal physical activity; morphometric measures; organ weights (absolute and relative) including brain, testicles and seminal vesicles in males 5 mo of age; and the O2 uptake of some brain and glandular structures in males at 5 mo of age. Body weight of the malnourished animals was consistently lower than that of the controls. Compared to controls sexual behavior in undernourished males was significantly reduced, while curiosity test and basal physical activity were increased. The absolute weights of all organs (except the pituitary gland) were significantly lower in malnourished males at 5 mo than in controls. Compared to controls, relative weight of brain was greater and that of seminal vesicles was less in the male rats. Oxygen uptake was significantly lower in the pituitary gland and testicles of malnourished males than of controls. In view of these results, it can be concluded that malnutrition in utero and while suckling affects fundamental parameters of both development and reproductive function in the male offspring 4 mo after feeding ad libitum is begun at weaning.

Animals↗
PubMed1996

Deletion of the Schizophyllum commune A alpha locus: the roles of A alpha Y and Z mating-type genes.

The A alpha locus is one of four master regulatory loci that determine mating type and regulate sexual development in Schizophyllum commune. We have made a plasmid containing a URA1 gene disruption of the A alpha Y1 gene. Y1 is the sole A alpha gene in A alpha 1 strains. We used the plasmid construction to produce an A alpha null (i.e., A alpha delta) strain by replacing the genomic Y1 gene with URA1 in an A alpha 1 strain. To characterize the role of the A alpha genes in the regulation of sexual development, we transformed various A alpha Y and Z alleles into A alpha delta strains and examined the acquired mating types and mating abilities of the transformants. These experiments demonstrate that the A alpha Y gene is not essential for fungal viability and growth, that a solitary Z A alpha mating-type gene does not itself activate development, that A beta proteins are sufficient to activate the A developmental pathway in the absence of A alpha proteins and confirm that Y and Z genes are the sole determinants of A alpha mating type. The data from these experiments support and refine our model of the regulation of A-pathway events by Y and Z proteins.

Gene Deletion↗
PubMedDate not supplied

Fish gonadotropin-releasing hormone gene and molecular approaches for control of sexual maturation: development of a transgenic fish model.

The prepro-GnRH gene and mRNA primary structure were fully established from Atlantic salmon (Salmo salar) and partially from rainbow trout (Oncorhynchus mykiss). Results show that the GnRH coding region of 30 base pairs is well conserved during evolution. In contrast, the GnRH-associated peptide (GAP) sequence shows very limited homology when the GnRH genes from mammalian and teleost species are compared. A simple method for selecting transgenic fish after transfer of the firefly luciferase gene was developed. The method involves bioluminescent measurement of live animals in a scintillation counter.

Amino Acid Sequence↗
PubMed1993

Gonadotropin-releasing hormone agonists in the treatment of girls with central precocious puberty.

The onset of puberty before the age of 8 years in a girl is considered precocious. A child who presents with premature sexual development requires a thorough history, physical examination, and appropriate laboratory evaluation. Making the correct diagnosis is crucial to the selection of the appropriate form of therapy and management. Generally, CPP is the result of premature activation of the hypothalamic-pituitary-gonadal axis and can be successfully managed with long-acting GnRH agonists. In addition, GnRH analogue therapy has been shown to be safe, effective, and reversible. Treatment has resulted in a delay in the progression of secondary sexual development, normalization of the growth velocity, slowing of the rate of bone maturation, and an increase in the predicted final adult height. The GnRH agonists are ineffective in the therapy of gonadotropin-independent precocious puberty.

Child↗
PubMed1999

Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial.

CONTEXT: Heterozygous familial hypercholesterolemia (HeFH) is a common disorder associated with early coronary artery disease, especially in men. The age at which drug therapy should be started is still controversial, as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). OBJECTIVE: To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH. DESIGN: One-year, double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial. In the first period (24 weeks), lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period (24 weeks). The study was conducted between 1990 and 1994. SETTING: Fourteen pediatric outpatient clinics in the United States and Finland. PATIENTS: Boys aged 10 to 17 years with HeFH. Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention, 59 placebo) and 110 (61 intervention, 49 placebo) completed the first and second periods, respectively. INTERVENTION: Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo. MAIN OUTCOME MEASURES: The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual development. RESULTS: Compared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (P<.001) by 17%, 24%, and 27% receiving dosages of 10, 20, and 40 mg/d, respectively, and remained 25 % lower than baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition. However, the study was underpowered to detect significant differences in safety parameters. Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C, the major carrier of vitamin E in the circulation. CONCLUSIONS: This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin. Comprehensive clinical and biochemical data on growth, hormonal, and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks, although further study is required.

Adolescent↗
PubMed1999

Prenatal melatonin influences developmental changes of tachykinins in response to estradiol benzoate.

The developmental changes of hypothalamic, pituitary, striatum and pineal gland tachykinin concentrations, as well as the response to estradiol-benzoate (EB) administration, were studied in offspring of control and melatonin (MEL) treated mother rats. Female rats were studied throughout different phases of the sexual development: infantile, prepubertal and pubertal periods, in the four following groups; control-offspring+vehicle; control-offspring+EB; MEL-offspring+vehicle; MEL-offspring+EB. Hypothalamic NKA in control-offspring+ vehicle was significantly increased only at 27 days of age and in control-offspring+EB at 27 days of age and during the infantile period. Hypothalamic SP levels increased similarly in control-offspring+EB during the infantile period but the EB influence was more pronounced with significantly increased concentrations at 32 days of age. Prenatal melatonin treatment produced major alterations in these patterns of postnatal development. In MEL-offspring+EB tachykinins concentrations in the hypothalamus during infantile and prepubertal periods did not increase, however at 37 days of age, they showed significantly higher values than in control-offspring+EB groups. The developmental pattern of pituitary NKA and SP concentrations in both; control-offspring+vehicle and control-offspring+EB groups, showed similar values from the infantile period to puberty, indicating that NKA and SP concentrations remained at similar levels independently of the sexual stage, only at 27 days of age in control-offspring+EB significantly increased values were found as compared to MEL-offspring+EB. Prenatal melatonin did not produce marked modifications, only significantly lower NKA and SP concentrations in MEL-offspring+EB group were observed at 25 days of age in comparison to control-offspring+EB group. Striatal NKA and SP concentrations showed a similar developmental pattern. In control-offspring, EB treatment produced NKA and SP decreased concentrations at the infantile period than in control-offspring+vehicle and significantly increased concentrations during the prepubertal period, then during the pubertal period NKA and SP concentrations decreased in control-group+EB. However, prenatal melatonin treatment reduced the levels of striatal NKA and SP during the prepubertal period after EB treatment and delayed until pubertal period the increase previously observed in control group during the prepubertal period. In MEL-offspring+vehicle group striatal concentrations of both tachykinins remained at low levels from infantile period until pubertal period. Prenatal melatonin and EB did not produce major alterations in SP pineal concentrations throughout sexual development. Plasma estradiol concentrations were significantly higher in the groups that received EB treatment than in those that received vehicle during prepubertal and juvenile periods in control-offspring+EB group and during the pubertal period in MEL-offspring+EB group. These data indicate that prenatal MEL treatment may influence NKA and SP developmental pattern from the infantile period until adulthood in the female rat.

Animals↗
PubMed2004

Effects of organotin compounds on pubertal male rats.

Tributyltin (TBT) and triphenyltin (TPT) induce effects in male and female reproductive organs of rodents. They also cause tumors in these organs and it is theorized that they result from endocrine disruption. We studied the effects of 40 mg methyltestosterone (MTT), 0.5 or 15 mg TBT and 2, 6 or 12 mg TPT/kg bw on the male sexual development using a modification of the Rodent 20-Day Thyroid/Pubertal Male Assay. Male Wistar rats were treated per gavage for 30 days beginning at 23 days of age. A delay in the completion of preputial separation was observed after administration of MTT and 15 mg/kg TBT. Changes in weights of one or more reproductive organs were observed in all treatment groups. Testosterone concentration was decreased in the MTT, the 15 mg TBT as well as in the 6 and 12 mg TPT groups. A decrease in luteinizing hormone (LH) concentration was observed in the MTT and 15 mg TBT groups while an increase was seen after exposure to 6 mg TPT/kg bw. We conclude that peripubertal exposure to 15 mg TBT and 6 mg TPT/kg bw clearly affected male sexual development.

Animals↗
PubMed2004

Immunocytochemical localization of cytochrome P450 aromatase in the testis of prepubertal, pubertal, and postpubertal horses.

The large amount of testicular estrogens produced by the stallion is unique compared to the amounts found in other domestic species. Although the cellular locale of the cytochrome P450 aromatase (P450arom) enzyme that converts C19 androgens to C18 estrogens has been identified in the Leydig cell of adult equine testis, the location in the immature equine testis is not known. The goal of this work was to localize the enzyme in colts and stallions during sexual development. Testes were obtained from prepubertal (n=7), pubertal (n=6), and postpubertal (n=8) colts and stallions during both the breeding and non-breeding seasons. Tissue was fixed and prepared for immunocytochemistry (ICC), carried out with an antiserum against human placental P450arom. In prepubertal colts, there was distinct immunopositive staining of a similar degree within both the Leydig cell and the seminiferous tubule. Horses in the pubertal group had strong Leydig cell immunopositive staining and a slight degree of positive staining within the seminiferous tubules. Postpubertal stallions exhibited definitive immunopositive staining within Leydig cells but not within the seminiferous tubules. Therefore, P450arom is present within the Leydig cell throughout sexual development. In contrast, the presence of P450arom within the seminiferous tubule based upon ICC appeared to be gone by adulthood, suggesting that an age-dependent shift in the locale of this enzyme as the stallion matures.

Animals↗
PubMed2000

Divergence in murine myometrium spontaneous and oxytocin-stimulated contractile responses to serine/threonine protein phosphatase-1 inhibition.

Reversible phosphorylation is essential in regulating uterine contractions. Identification, characterization, and functional understanding of myometrium protein phosphatase(s) are lacking. Okadaic acid (OA), which inhibits protein phosphatase-1 (PP1) and PP2A, has been shown to alter uterine contractions. Experiments were conducted to determine the 1) identity of the myometrial OA-sensitive PP, 2) influence of OA on spontaneous and oxytocin (OT)-stimulated myometrial contractions, and 3) expression of uterine PPs during sexual development. Western blot analysis indicated the presence of PP1(alpha) and PP2A in immature and mature mice. As determined by immunohistochemistry, gonadotropin-stimulated adult mouse uteri contain PP1(alpha) in longitudinal and circular myometrial layers and endometrial epithelium. Conversely, PP2A was localized to the endometrial stroma. Cumulative addition of OA (n = 9; 10, 100, 250, 500, 1000 nM) did not significantly alter spontaneous contractions of mouse uterine horns in comparison to vehicle-treated controls (n = 9). By the end of the test period OA- and vehicle-treated uteri displayed a comparable decline in uterine contractions to 79.2% and 63.7%, respectively, of basal contractile activity. Pretreatment of uterine tissue with OA (1 microM; n = 7) significantly reduced contractile response to increasing concentrations of OT (8, 16, 32, 64 nM) in comparison to vehicle pretreatment (dimethyl sulfoxide; n = 7). At the end of the OT-administration period, contractile activity was 160.4% and 67.3% of basal contractile activity for vehicle (no OA) and OA-pretreated groups, respectively. During the early prepubertal period PP1(alpha) was expressed in longitudinal myometrium and absent in circular myometrium; whereas, during the transition to sexual maturity PP1(alpha) was observed in both the longitudinal and circular myometrium. In summary, these studies have indicated 1) that PP1 is the primary myometrial OA-sensitive PP; 2) that inhibition of PP1 had no effect on spontaneous contractions, whereas it markedly inhibited OT-stimulated uterine contractions; and 3) that PP1 is differentially expressed in the circular and longitudinal myometrium in relation to sexual development.

Animals↗
PubMed1991

46,XY pure gonadal dysgenesis with gonadoblastoma. A case report.

46,xy pure gonadal dysgenesis is a rare disorder, which is characterized by female phenotype, infantile female external genitalia, deficient secondary sexual development, hypoplastic uterus and fallopian tubes, and streak gonads. A 17-year-old female phenotypic patient was admitted due to primary amenorrhea, who also had poor breast development, deficient axillary and pubic hairs, and infantile female external genitalia. Lymphocyte culture of peripheral blood for chromosome study revealed 46,XY normal male karyotype. Endocrine evaluation demonstrated low estrogen, high LH and FSH levels, and normal testosterone level of female range. According to the high risk of germ cell tumor occurrence in 46,XY gonadal dysgenesis, bilateral salpingo-oophorectomy and total hysterectomy were performed. Pathology of the left ovary revealed gonadoblastoma accidentally. Thereafter, she received regular hormone therapy and had generally felt well. Secondary sexual development was noted one year later.

Adolescent↗
PubMed2000

The fission yeast TOR homolog, tor1+, is required for the response to starvation and other stresses via a conserved serine.

Targets of rapamycin (TORs) are conserved phosphatidylinositol kinase-related kinases that are involved in the coordination between nutritional or mitogenic signals and cell growth. Here we report the initial characterization of two Schizosaccharomyces pombe TOR homologs, tor1(+) and tor2(+). tor2(+) is an essential gene, whereas tor1(+) is required only under starvation and other stress conditions. Specifically, Deltator1 cells fail to enter stationary phase or undergo sexual development and are sensitive to cold, osmotic stress, and oxidative stress. In complex with the prolyl isomerase FKBP12, the drug rapamycin binds a conserved domain in TORs, FRB, thus inhibiting some of the functions of TORs. Mutations at a conserved serine within the FRB domain of Saccharomyces cerevisiae TOR proteins led to rapamycin resistance but did not otherwise affect the functions of the proteins. The S. pombe tor1(+) exhibits different features; substitution of the conserved serine residue, Ser(1834), with arginine compromises its functions and has no effect on the inhibition that rapamycin exerts on sexual development in S. pombe.

Amino Acid Sequence↗