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Involvement of arginine vasotocin in reproductive events in the male newt Cynops pyrrhogaster.

Effects of arginine vasotocin (AVT) on reproductive events such as courtship behavior, pheromone release, and spermatophore discharge were investigated in the male newt Cynops pyrrhogaster. AVT enhanced the incidence and frequency of androgen-induced courtship behavior. In this case, AVT was likely to act centrally because the behavior was evoked with a much smaller amount of AVT when the hormone was administered intracerebroventricularly than when given intraperitoneally. Involvement of endogenous AVT in spontaneously occurring courtship behavior was also evidenced by the fact that administration of a V1 (vasopressor) receptor antagonist, [d(CH2)5(1), Tyr(Me)2, Arg8-vasopressin] suppressed the expression of the courtship behavior. The water in which AVT-treated males had been kept showed considerable female-attracting activity as compared with the water in which saline-injected males had been kept. Moreover, the content of sodefrin, a female-attracting pheromone in the abdominal gland, was decreased by the intraperitoneal injection of AVT, suggesting that the neurohypophyseal hormone stimulated the release of sodefrin from the abdominal gland into the water. AVT induced contraction of the excised abdominal gland concentration-dependently, and, again, the V1 receptor antagonist suppressed the AVT-induced contraction. Thus, we concluded that AVT induces the pheromone discharge, acting peripherally on a contractile structure of the abdominal gland. AVT was also found to induce spermatophore deposition in the male kept in the absence of the female. Administration of the V1 receptor blocker to the sexually developed males suppressed the spermatophore deposition. All these results indicate the involvement of AVT in reproductive events acting centrally and peripherally.

Animals↗

ASD4, a new GATA factor of Neurospora crassa, displays sequence-specific DNA binding and functions in ascus and ascospore development.

A new gene encoding a novel GATA factor, ASD4, of Neurospora crassa was isolated and demonstrated to possess one intron and to specify an open reading frame encoding a protein with 427 amino acid residues. The ASD4 protein contains a single GATA-type zinc finger and a putative coiled-coil domain. Unlike related proteins, DAL80 in yeast and NREB in Penicillium, ASD4 does not appear to be involved in regulation of nitrogen metabolism. An Asd-4 null mutant obtained by the rip procedure did not show any effect upon nitrogen control, but instead resulted in severe defects in ascus and ascospore genesis. The Asd-4 rip mutant is dominant to Asd-4+. A cross of the Asd-4 mutant with wild-type resulted in fruiting bodies that appeared to be normal macroscopically but which were complete devoid of asci and ascospores. Introduction of the Asd-4+ gene into the Asd-4 rip mutant corrected the defect in ascus and ascospore development in crosses with wild-type. Mobility shift assays demonstrated that ASD4 acts as a sequence-specific DNA binding protein and recognizes DNA fragments that contain GATA core elements. Gel filtration and cross-linking experiments revealed that the ASD4 protein exists as a tetramer in solution. These results suggest that the ASD4 protein functions positively as a transcriptional regulator of sexual development in Neurospora.

Blotting, Northern↗

Influence of preoperative parenteral alimentation on postoperative growth in adolescent Crohn's disease.

The postoperative growth rates achieved in eight early pubertal adolescent males with Crohn's disease undergoing surgery for obstructive complications is reported as a function of the use of 1 month's preoperative central venous alimentation. All patients had ileal strictures with ileocolitis, bone ages less than 13, Tanner stages 1 or 2, and growth velocities below the 3rd percentile for age. During a 3-year follow-up, those receiving preoperative venous alimentation demonstrated greater oral caloric intake (significant for 1 year) and greater postoperative growth velocity (significant for 2 years) in comparison to those patients who did not receive preoperative venous alimentation. There was no significant difference between the two groups of patients in postoperative weight gain, sexual development, and 3-year disease control.

Adolescent↗

DMRT1/Dmrt1, the sex determining or sex differentiating gene in Vertebrata.

Although the phenomenon of sexual dimorphism is widespread in vertebrates, the molecular mechanism of sex-determination is not the same across animal phyla, in contrast to other areas of developmental biology. Recent extensive studies, however, have given proof of evolutionarily conserved function in genes which share a novel DNA binding DM domain, primarily identified in two invertebrate sex regulatory genes: doublesex of Drosophila melanogaster and mab-3 of Caenorhabditis elegans. Their mammalian autosomal homologue, DMRT1, first isolated in humans, was further discovered in genomes of various vertebrate species and appears to be involved in similar aspects of sexual development. Its precise role is still speculated, thus identification of sex reversal mutations, functional studies as well as determination of the sex-specific expression profile during embryogenesis are still being undertaken. Is this a sex determining rather than a sex differentiating gene? Is it involved in a dosage-sensitive mechanism? On what level does it function in the hierarchy of the sexual regulatory gene cascade? Recent results are discussed in this paper.

Animals↗

[Chromosomic etiology of male sterility and infertility].

Recent advances in the knowledge of sexual development have been obtained by studying individuals with dysgenetic gonads and reproductive tract alterations. By using probes Y-ADN in these patients, it was found that a gene of the short arms of Y chromosome, induces testicular differentiation. The way this gene acts is not known, but the observation that there are homologue sequencies in X and Y, suggests the possibility that sexual differentiation depends on genic doses. Other genes like the one that codifies for antigen H-Y, for skeletal maturation, body growth, dental size and spermatogenesis regulation, have been identified in chromosome Y. Findings that have allowed a better understanding of genetic and cytogenetic factor involved in sterility-infertility.

Humans↗

[Malaria: from genetic and molecular biology to disease control].

The knowledge of the genomic structure of Plasmodium falciparum and of its main vector, Anopheles gambiae, may offer new perspectives for malaria therapy, vaccines or control of mosquito-borne transmission. New targets for future antimalarial drugs were identified, mainly apicoplast (a vestige of a vegetal structure incorporated by the parasite) and several enzymes, particularly proteases. The practical difficulty is now to select a few number of these "promising molecules", probably no more than 3 or 4, for a preclinical and clinical pharmaceutical development. Indeed, several other antimalarial drugs are already under development, and the industrial possibilities for developing new drugs are evidently limited. Many new vaccination targets and antigenic proteins were also identified. According to scientific and industrial limitations, a complete evaluation of these antigens is absolutely necessary to select a few of them for clinical development. For anti-malarial vaccinations, DNA vaccines may offer the most interesting perspectives, with the possibility of simultaneous immunisation against different Plasmodium stages and of an adjuvant effect by adding a gene encoding certain cytokines. In Anopheles gambiae genome, several genes encoding key-proteins (particularly odorant receptors necessary for blood feeding) were identified, as other genes encoding for proteins limiting the sexual development of Plasmodium inside its vector. From a theoretical viewpoint, genetically modified non biting or non transmitting mosquitoes offer new perspectives for the control of malaria transmission, but until now, the preliminary practical attempts gave rather poor results. On the whole, the genomic and proteomic of Plasmodium falciparum and Anopheles gambiae yielded exciting scientific results, but it is still too early and very speculative to imagine their practical applications for the control of malaria.

Animals↗

Sexual maturation, social class, and the desire to be thin among adolescent females.

Veblen's 1899 hypothesis that associated a female desire for thinness with the higher social classes was tested with data from a representative national sample of adolescents, 12 to 17 years of age, in the National Health Examination Survey. Controlling for the actual level of fatness, adolescent females in higher social classes wanted to be thinner more often than those in lower classes. The greater female desire for thinness was not the product of health information nor of sex differences in the level of fatness. The thinner the female, the greater the impact of social class on the desire for thinness. During puberty, adolescent females negatively evaluated the body fat associated with normal sexual development.

Adolescent↗

Differential effect of race on the axial and appendicular skeletons of children.

The prevalence of osteoporosis and the incidence of fractures are substantially lower in black than in white subjects, a finding generally attributed to racial differences in adult bone mass. Whether these racial differences are present in childhood is the subject of considerable interest, as the amount of bone gained during growth is a major determinant of future susceptibility to fractures. We measured the density and size of the vertebrae and femurs of 80 black and 80 white healthy children, 8-18 yr of age, matched for age, gender, height, weight, and stage of sexual development, using computed tomography. Race had a significant and differential effect on the bones in the axial and appendicular skeletons. In the axial skeleton, black children had greater cancellous bone density, but similar cross-sectional area of the vertebral bodies. In contrast, in the appendicular skeleton, black children had greater femoral cross-sectional area, but similar cortical bone area and cortical bone density. Compared to white children, vertebral bone density and femoral cross-sectional area at sexual maturity were, on the average, 10.75% and 5.7% higher, respectively, in black children. Such significant variations may contribute to the racial differences in the prevalence of osteoporosis between black and white adults.

Adolescent↗

[Cranial irradiation induces premature activation of the gonadotropin-releasing-hormone].

BACKGROUND: CNS-irradiation in prepubertal children with leukemia or brain tumors can lead to precocious or in high doses to delayed puberty. The underlying mechanisms of these disorders are unknown. METHODS: A new animal model of experimentally induced pubertal disorders by cranial irradiation has been developed. In infantile or juvenile (12 - 23 days old) female rats precocious or delayed puberty have been induced by selective cranial Co60-irradiation (4 - 18 Gy). At age of 32 - 38 days or 3 months relevant hormone parameters have been studied basal and after stimulated conditions. RESULTS: Low radiation doses (5 or 6 Gy) led to accelerated onset of puberty as well as elevated LH- and estradiol levels. High radiation doses (9 - 18 Gy) caused retardation of sexual development, lower gonadotropin levels and growth retardation associated with growth hormone deficiency. After cranial irradiation with 5 Gy the release rates of the inhibitory neurotransmitter gamma-aminobutyric-acid (GABA) from hypothalamic explants were significantly lower (p < 0,05). The gonadotropin-releasing-hormone (GnRH) expression in the hypothalamic preoptic area of irradiated animals (5 Gy) was significantly higher than in controls (p < 0,05). CONCLUSION: The GnRH-pulse generator is very radiosensitive as low dose irradiation causes precocious puberty, whereas high dose irradiation is associated with delayed sexual maturation. Radiation induced precocious puberty might be caused by damage to inhibitory GABAergic neurons leading to desinhibition and premature activation of GnRH neurons. Our animal model of cranial irradiation seems to be suitable to study neurotransmitter disorders, molecular mechanisms and potential preventive intervention of radiation induced pubertal changes.

Abnormalities, Radiation-Induced↗

Analysis of progesterone receptor in the quail oviduct. Correlation between plasmatic estradiol and cytoplasmic progesterone receptor concentrations.

Specific binding sites for [3H]-progesterone are found in the cytosol fraction of the oviduct of castrated, immature and developing quails. The optimal conditions to accurately measure the total cytoplasmic concentration of this progesterone receptor are described. The dissociation constant (KD) at 0 degrees C is 3.6 +/- 0.6 x 10(-9) M (mean +/- SE) for [3H]-P and the concentration of binding sites is 13.4 +/- 2 pmol/mg DNA in immature animals. This binding capacity is not altered even 2 weeks after ovariectomy. During sexual development, although the dissociation constant remains unchanged, the number of binding sites increases to 74.5 +/- 1.6 pmol/mg DNA just before the beginning of the laying cycle. The concentration of cytoplasmic P receptor is under the inductive influence of estradiol. In castrated quails, estradiol 17 beta (E2) perfusion through the portal vein at a rate below or equal to 2 ng/min for 24 hr does not increase plasmatic E2 concentration and consequently does not change [3H]-P binding sites concentration in the oviduct. While E2 perfusion rate exceeds the metabolizing capacity of the liver (6.8 ng/min), both plasmatic E2 level and oviductal P receptor concentration are increased. When E2 is perfused through the jugular vein, plasmatic E2 level increases with the dose of E2 but P receptor concentration only increases when E2 perfusion rate reaches to 2.0 ng/min for 24 h.

Animals↗

College students' perceptions of the prevalence of risky sexual behaviour.

In contrast to previous research which has largely focused on students' perceptions of other students' risk for contracting HIV/STDs, this study assessed single heterosexual college students' (96 men, 121 women) perceptions of the prevalence of different sexual behaviours which increase a person's risk for HIV/STD infection (e.g. multiple sexual partners, unprotected sexual intercourse, one-time sexual encounters). Consistent with previous research which has demonstrated an overestimation bias in judging others' risk for HIV/STD infection, students' estimates about the prevalence of sexual behaviours increasing a person's risk for HIV/STD infection were similarly overestimated relative to reported base rates. Gender differences were also observed. Although women generally tended to give higher prevalence estimates than men, overall, participants gave higher estimates when judging the behaviour of men compared to women. Both motivational and cognitive explanations of our data are discussed. Our findings highlight the importance of developing sexual risk reduction programmes which (a) enable students to make more accurate personal risk judgements, (b) increase students' awareness of the riskiness of their own sexual behaviours, and (c) promote positive health changes (e.g. increased condom use) in normative sexual behaviour among college students.

Adult↗

Developmental effects of dietary phytoestrogens in Sprague-Dawley rats and interactions of genistein and daidzein with rat estrogen receptors alpha and beta in vitro.

Estrogenic isoflavones, such as genistein and daidzein, are present in virtually all natural-ingredient rodent diets that use soy as a source of protein. Since these compounds are endocrine-active, it is important to determine whether the amounts present in rodent diets are sufficient to affect sexual development. The present study consisted of in vitro and in vivo parts. In the in vitro portion, human hepatoma cells were transfected with either rat estrogen receptor (ER) alpha or beta plus an estrogen-responsive luciferase reporter gene. Genistein and daidzein were complete agonists at both ERs, genistein being more potent than daidzein, and both compounds were more potent at ER beta than ER alpha. In combined studies with estradiol, genistein exerted additive effects with estradiol in vitro. In the in vivo portion of the study, groups of six pregnant Sprague-Dawley females were fed one of the following four diets, and the pups were maintained on the same diets until puberty: (1) a natural-ingredient, open-formula rodent diet (NIH-07) containing 16 mg genistein and 14 mg daidzein per 100 g of feed; (2) a soy- and alfalfa-free diet (SAFD) in which casein and corn oil were substituted for soy and alfalfa meal and soy oil, respectively, that contained no detectable isoflavones; (3) SAFD containing 0.02% genistein (GE.02); or (4) SAFD containing 0.1% genistein (GE.1). In the GE.1 group, effects of dietary genistein included a decreased rate of body-weight gain, a markedly increased (2.3-fold) uterine/body weight (U/BW) ratio on postnatal day (pnd) 21, a significant acceleration of puberty among females, and a marginal decrease in the ventral prostate weight on postnatal day (pnd) 56. However, developmental differences among the groups fed SAFD, GE.02, or NIH-07 were small and suggested minimal effects of phytoestrogens at normal dietary levels. In particular, on pnd 21, the U/BW ratio of the GE.02 and NIH-07 groups did not differ significantly from that of the SAFD group. Only one statistically significant difference was detected between groups fed SAFD and NIH-07: the anogenital distance (AGD) of female neonates on pnd 1 whose dams were fed NIH-07 was 12% larger than that of neonates whose dams were fed SAFD. The results suggest that normal amounts of phytoestrogens in natural-ingredient rodent diets may affect one developmental parameter, the female AGD, and that higher doses can affect several other parameters in both males and females. Based on these findings, we do not suggest replacing soy- and alfalfa-based rodent diets with phytoestrogen-free diets in most developmental toxicology studies. However, phytoestrogen-free diets are recommended for endocrine toxicology studies at low doses, to determine whether interactive effects may occur between dietary phytoestrogens and man-made chemicals.

Animals↗

Cytosol estradiol receptor content in the adult rat brain after neonatal treatment with estradiol benzoate or testosterone propionate.

The effects of neonatal treatment with estrogen or androgen on the development of cytosol estradiol (E2) receptors were examined in the rat pituitary, hypothalamus and amygdala. The treatment with estradiol benzoate (EB, 100 micrograms) significantly reduced the E2 receptor content in all of these regions in both sexes. But the treatment with testosterone propionate (TP, 1 mg) to the female rats significantly decreased the E2 receptor content in the pituitary and hypothalamus but not in the amygdala. The TP treatment to the male rats decreased the E2 receptor content in the hypothalamus and amygdala but not in the pituitary. The decreased cytosol E2 receptors in the hypothalamus and amygdala seem to be implicated in preventing the normal sexual development.

Amygdala↗

Expression of three gene families encoding cell-cell communication molecules in the prepubertal nonhuman primate hypothalamus.

Transsynaptic and glial-neuronal communication are important components of the mechanism underlying the pubertal activation of luteinizing hormone-releasing hormone (LHRH) secretion. The molecules required for the architectural organization of these cell-cell interactions have not been identified. We now show that the hypothalamus of the prepubertal female rhesus monkey expresses a multiplicity of genes encoding three families of adhesion/signalling proteins involved in the structural definition of both neurone-to-neurone and bi-directional neurone-glia communication. These include the neurexin/neuroligin (NRX/NRL) and protocadherin-alpha (PCDHalpha) families of synaptic specifiers/adhesion molecules, and key components of the contactin-dependent neuronal-glial adhesiveness complex, including contactin/F3 itself, the contactin-associated protein-1 (CASPR1), and the glial receptor protein tyrosine phosphatase beta. Prominently expressed among members of the NRX family is the neurexin isoform involved in the specification of glutamatergic synapses. Although NRXs, PCDHalphas and CASPR1 transcripts are mostly detected in neurones, the topography of expression appears different. NRX1 mRNA-containing neurones are scattered throughout the hypothalamus, PCDHalpha mRNA transcripts appear more abundant in neurones of the arcuate nucleus and periventricular region, and neurones positive for CASPR1 mRNA exhibit a particularly striking distribution pattern that delineates the hypothalamus. Examination of LHRH neurones, using the LHRH-secreting cell line GT1-7, showed that these cells contain transcripts encoding NRXs and one of their ligands (NRL1), at least one PCDHalpha (CNR-8/PCDHalpha10), and the CASPR1/contactin complex. The results indicate that the prepubertal female monkey hypothalamus contains a plethora of adhesion/signalling molecules with different but complementary functions, and that an LHRH neuronal cell line expresses key components of this structural complex. The presence of such cell-cell communication machinery in the neuroendocrine brain suggests an integrated participation of their individual components in the central control of female sexual development.

Animals↗

Familial hypercholesterolemia in children.

PURPOSE OF THIS REVIEW: This review provides an update on recent advances in the diagnosis and management of children with familial hypercholesterolemia. RECENT FINDINGS: A large cross-sectional cohort study of paediatric familial hypercholesterolemia demonstrated that affected children had a 5-fold more rapid increase of carotid arterial wall intima-media thickness during childhood years than their affected siblings. This faster progression led to a significant deviation in terms of intima-media thickness from the age of 12 years and onwards. Low-density lipoprotein cholesterol was a strong and independent predictor of carotid artery intima-media thickness in these children, which confirms the pivotal role of low-density lipoprotein cholesterol for the development of atherosclerosis. In this condition lipid lowering by statin therapy is accompanied by carotid intima-media thickness regression in familial-hypercholesterolemic children, which suggests that initiation of low-density lipoprotein cholesterol-reducing medication in childhood already can inhibit or possibly reduce the faster progression of atherosclerosis. Furthermore, these trials demonstrated that statins are safe and do not impair growth or sexual development in these children. Conversely, products containing plant sterols reduced low-density lipoprotein cholesterol levels by 14%, but did not improve endothelial dysfunction as assessed by flow-mediated dilatation. SUMMARY: Children with familial hypercholesterolemia clearly benefit from lipid-lowering strategies. Statins are safe agents and have been proven to reduce elevated low-density lipoprotein cholesterol levels significantly. In addition, statins improve surrogate markers for atherosclerosis. Therefore these agents should become the pivotal therapy in children with familial hypercholesterolemia.

Adolescent↗

Divergent cAMP signaling pathways regulate growth and pathogenesis in the rice blast fungus Magnaporthe grisea.

cAMP is involved in signaling appressorium formation in the rice blast fungus Magnaporthe grisea. However, null mutations in a protein kinase A (PKA) catalytic subunit gene, CPKA, do not block appressorium formation, and mutations in the adenylate cyclase gene have pleiotropic effects on growth, conidiation, sexual development, and appressorium formation. Thus, cAMP signaling plays roles in both growth and morphogenesis as well as in appressorium formation. To clarify cAMP signaling in M. grisea, we have identified strains in which a null mutation in the adenylate cyclase gene (MAC1) has an unstable phenotype such that the bypass suppressors of the Mac1(-) phenotype (sum) could be identified. sum mutations completely restore growth and sexual and asexual morphogenesis and lead to an ability to form appressoria under conditions inhibitory to the wild type. PKA assays and molecular cloning showed that one suppressor mutation (sum1-99) alters a conserved amino acid in cAMP binding domain A of the regulatory subunit gene of PKA (SUM1), whereas other suppressor mutations act independently of PKA activity. PKA assays demonstrated that the catalytic subunit gene, CPKA, encodes the only detectable PKA activity in M. grisea. Because CPKA is dispensable for growth, morphogenesis, and appressorium formation, divergent catalytic subunit genes must play roles in these processes. These results suggest a model in which both saprophytic and pathogenic growth of M. grisea is regulated by adenylate cyclase but different effectors of cAMP mediate downstream effects specific for either cell morphogenesis or pathogenesis.

Alleles↗

A MADS box protein interacts with a mating-type protein and is required for fruiting body development in the homothallic ascomycete Sordaria macrospora.

MADS box transcription factors control diverse developmental processes in plants, metazoans, and fungi. To analyze the involvement of MADS box proteins in fruiting body development of filamentous ascomycetes, we isolated the mcm1 gene from the homothallic ascomycete Sordaria macrospora, which encodes a putative homologue of the Saccharomyces cerevisiae MADS box protein Mcm1p. Deletion of the S. macrospora mcm1 gene resulted in reduced biomass, increased hyphal branching, and reduced hyphal compartment length during vegetative growth. Furthermore, the S. macrospora Deltamcm1 strain was unable to produce fruiting bodies or ascospores during sexual development. A yeast two-hybrid analysis in conjugation with in vitro analyses demonstrated that the S. macrospora MCM1 protein can interact with the putative transcription factor SMTA-1, encoded by the S. macrospora mating-type locus. These results suggest that the S. macrospora MCM1 protein is involved in the transcriptional regulation of mating-type-specific genes as well as in fruiting body development.

Amino Acid Sequence↗

Effects of progesterone and synthetic luteinizing hormone releasing hormone on the release of luteinizing hormone during sexual maturation in the hen (Gallus domesticus).

Single intramuscular injections of 0-5 mg progesterone/kg resulted in increased LH secretion in laying hens but not in pullets with completely undeveloped sexual organs. Injections of the steroid were first able to stimulate LH release 8-10 weeks before the onset of lay when the comb, ovary and oviduct had started to grow and basal plasma LH concentrations were beginning to rise. At this time, injecitons of 10 mug synthetic LH-RH/kg resulted in an incremental change in plasma LH levels of around 26 ng/ml. A similar incremental change was observed after giving the same dose of LH-RH to pullets with no signs of sexual development. Three to four weeks before the first eggs were laid, basal plasma LH levles started to fall, the pituitary became progressively more insensitive to synthetic LH-RH and injections of 0-5 mg progesterone/kg resulted in a reduced LH response. Ten mug LH-RH/kg caused incremental changes in blood levels of LH of less than 5 ng/ml. The final stage of sexual maturation occurred during the week before the onset of lay and was characterized by a rapid growth of large yolky ovarian follicles and a further fall in the sensitivity of the pituitary to synthetic LH-RH. However, injections of 0-5 mg progesterone/kg resulted in a prolonged release of LH. These observations are discussed in relation to the maturatio of the positive feedback mechanism by which progesterone stimulates the secretion of LH.

Animals↗