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PubMed1985

An epidemic of precocious development in Puerto Rican children.

An alarming incidence of premature sexual development has been reported in Puerto Rico during the last 7 years. A significant increment of premature thelarche, premature pubarche, prepubertal breast enlargement in boys, and precocious pseudopuberty in girls has been observed throughout the island. Several food specimens analyzed by chromatography and cytosol receptor assay revealed significant levels of estradiol equivalent in some meat samples. We suspect that the early sexual development is caused by exogenous estrogen contamination in the food ingested by the children and by their mothers.

Breast↗
PubMed1998

An RNA binding protein negatively controlling differentiation in fission yeast.

The fission yeast Schizosaccharomyces pombe starts sexual development when starved for nutrients and simultaneously activated by mating pheromones. We have identified a new gene regulating the onset of this process. This gene, called nrd1(+), encodes a typical RNA binding protein that preferentially binds poly(U). Deletion of nrd1(+) causes cells to initiate sexual development without nutrient starvation. We have found that the biological role of nrd1(+) is to block the onset of sexual development by repressing the Ste11-regulated genes essential for conjugation and meiosis until cells reach a critical level of starvation.

Amino Acid Sequence↗
PubMed2001

TTF-1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion.

TTF-1 is a member of the Nkx family of homeodomain genes required for morphogenesis of the hypothalamus. Whether TTF-1, or other Nkx genes, contributes to regulating differentiated hypothalamic functions is not known. We now report that postnatal hypothalamic TTF-1 expression is developmentally regulated and associated with the neuroendocrine process of female sexual development. Lesions of the hypothalamus that cause sexual precocity transiently activate neuronal TTF-1 expression near the lesion site. In intact animals, hypothalamic TTF-1 mRNA content also increases transiently, preceding the initiation of puberty. Postnatal expression of the TTF-1 gene was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and preproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothalamus, which restrain sexual maturation and facilitate reproductive behavior. TTF-1 mRNA was also detected in astrocytes of the median eminence and ependymal/subependymal cells of the third ventricle, where it colocalized with erbB-2, a receptor involved in facilitating sexual development. TTF-1 binds to and transactivates the erbB-2 and LHRH promoters, but represses transcription of the preproenkephalin gene. The singular increase in hypothalamic TTF-1 gene expression that precedes the initiation of puberty, its highly specific pattern of cellular expression, and its transcriptional actions on genes directly involved in neuroendocrine reproductive regulation suggest that TTF-1 may represent one of the controlling factors that set in motion early events underlying the central activation of mammalian puberty.

Aging↗
PubMed1982

Development of sexual dimorphism in the suprachiasmatic nucleus of the rat.

Synapses develop at similar rates in the suprachiasmatic nucleus of rats of both sexes, but values are higher in male than in female animals from birth to maturity. Male-type development cannot be mimicked by neonatal androgenization but results suggest that female-type development can be induced by neonatal castration of males. The results suggested that both prenatal and postnatal androgens are essential to normal male development.

Animals↗
PubMed2004

Fission yeast homolog of neuronal calcium sensor-1 (Ncs1p) regulates sporulation and confers calcium tolerance.

The neuronal calcium sensor (NCS) proteins (e.g. recoverin, neurocalcins, and frequenin) are expressed at highest levels in excitable cells, and some of them regulate desensitization of G protein-coupled receptors. Here we present NMR analysis and genetic functional studies of an NCS homolog in fission yeast (Ncs1p). Ncs1p binds three Ca2+ ions at saturation with an apparent affinity of 2 microm and Hill coefficient of 1.9. Analysis of NMR and fluorescence spectra of Ncs1p revealed significant Ca2+-induced protein conformational changes indicative of a Ca2+-myristoyl switch. The amino-terminal myristoyl group is sequestered inside a hydrophobic cavity of the Ca2+-free protein and becomes solvent-exposed in the Ca2+-bound protein. Subcellular fractionation experiments showed that myristoylation and Ca2+ binding by Ncs1p are essential for its translocation from cytoplasm to membranes. The ncs1 deletion mutant (ncs1Delta) showed two distinct phenotypes: nutrition-insensitive sexual development and a growth defect at high levels of extracellular Ca2+ (0.1 m CaCl(2)). Analysis of Ncs1p mutants lacking myristoylation (Ncs1p(G2A)) or deficient in Ca2+ binding (Ncs1p(E84Q/E120Q/E168Q)) revealed that Ca2+ binding was essential for both phenotypes, while myristoylation was less critical. Exogenous cAMP, a key regulator for sexual development, suppressed conjugation and sporulation of ncs1Delta, suggesting involvement of Ncs1p in the adenylate cyclase pathway turned on by the glucose-sensing G protein-coupled receptor Git3p. Starvation-independent sexual development of ncs1Delta was also complemented by retinal recoverin, which controls Ca2+-regulated desensitization of rhodopsin. In contrast, the Ca2+-intolerance of ncs1Delta was not affected by cAMP or recoverin, suggesting that the two ncs1Delta phenotypes are mechanistically independent. We propose that Schizosaccharomyces pombe Ncs1p negatively regulates sporulation perhaps by controlling Ca2+-dependent desensitization of Git3p.

Alleles↗
PubMed1991

Effects of prepubertal manipulation with androgens on the development of sexual differences in the harderian glands of Syrian hamsters.

The onset of sexual differences in the metabolism of porphyrins and melatonin in the Harderian glands of Syrian hamsters was studied. Three weeks after birth, the porphyrin concentrations were already higher in glands of females than in those of males. Castration of 22-day-old male hamsters led to an increase in Harderian porphyrin concentrations, although the levels of intact females were not reached. The administration of testosterone to 22-day-old female hamsters resulted in a marked decrease in porphyrin concentrations. Study of the development of sexual differences in the enzymes involved in melatonin synthesis, N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) indicated that not all the sexual differences observed in these glands begin at the same time. Thus, while differences in NAT activity were detected after the age of 3 weeks, male-female differences in HIOMT activity were only observed after 7 weeks. Castration of prepubertal male hamsters lowered NAT but not HIOMT activities. The administration of testosterone to prepubertal female hamsters led to male activity levels in both enzymes. Although circulating androgens seem to have a crucial role in maintaining sexual differences, other hormones including those from the pituitary and thyroid glands are probably also important for generating these sexual differences.

Acetylserotonin O-Methyltransferase↗
PubMed2001

Action of leptin on in vitro luteinizing hormone release in the European sea bass (Dicentrarchus labrax).

The discovery of leptin has sparked a rapidly growing number of publications concerning the role of leptin in the regulation of body adiposity, feeding, and reproductive system in mammals. To date, there have been no reports on the presence of leptin-related peptide, and functional studies on the role of leptin remain limited in fishes. We investigated the effect of mouse recombinant leptin on basal and sea bream (sb) GnRH-induced LH release from dispersed pituitary cells obtained from male European sea bass (Dicentrarchus labrax) at different stages of sexual development. The potential interaction of leptin with the porcine neuropeptide Y (pNPY), known to play a dual role in feeding and reproduction in vertebrates, was also investigated. High doses of leptin (10(-8)-10(-6) M) and/or pNPY (0.1 and 1 nM) had different effects on LH release at various stages of sexual development. Porcine NPY alone was weakly effective on basal LH release, but it enhanced LH release induced by leptin (10(-6) M) in late prepuberty but not in early postpuberty. Additive or inhibitory effects of leptin were observed on sbGnRH-induced LH release depending on sbGnRH dose and stage of sexual development. The direct action of leptin on LH release at the pituitary level in sea bass suggests that leptin is a regulator of the reproductive system in fishes.

Animals↗
PubMed1999

Similarity of DNA binding and transcriptional regulation by Caenorhabditis elegans MAB-3 and Drosophila melanogaster DSX suggests conservation of sex determining mechanisms.

Although most animals occur in two sexes, the molecular pathways they employ to control sexual development vary considerably. The only known molecular similarity between phyla in sex determination is between two genes, mab-3 from C. elegans, and doublesex (dsx) from Drosophila. Both genes contain a DNA binding motif called a DM domain and they regulate similar aspects of sexual development, including yolk protein synthesis and peripheral nervous system differentiation. Here we show that MAB-3, like the DSX proteins, is a direct regulator of yolk protein gene transcription. We show that despite containing different numbers of DM domains MAB-3 and DSX bind to similar DNA sequences. mab-3 mutations deregulate vitellogenin synthesis at the level of transcription, resulting in expression in both sexes, and the vitellogenin genes have potential MAB-3 binding sites upstream of their transcriptional start sites. MAB-3 binds to a site in the vit-2 promoter in vitro, and this site is required in vivo to prevent transcription of a vit-2 reporter construct in males, suggesting that MAB-3 is a direct repressor of vitellogenin transcription. This is the first direct link between the sex determination regulatory pathway and sex-specific structural genes in C. elegans, and it suggests that nematodes and insects use at least some of the same mechanisms to control sexual development.

Amino Acid Sequence↗
PubMed1983

The influence of siblings on the development of sexual preferences of male zebra finches.

Broods of young zebra finches were either raised by their own species or cross-fostered by Bengalese finches. Both were isolated visually from other birds at the age of 2 months. Sexual preferences of males were examined at maturity, in a choice between 1 zebra finch female and 1 Bengalese finch female, by measuring the number of song strophes directed at each. Males raised by their own species sang exclusively for the zebra finch female. Cross-fostered males raised without siblings or with only 1 sibling sand exclusively for the Bengalese finch female. A large number of cross-fostered males raised with 2-4 siblings showed at least 5% singing for the zebra finch female, and a small number did so predominantly. It is concluded that under the conditions of these experiments, the development of sexual preferences of zebra finch males is affected by both parental and sibling influences. It is possible that the earlier evidence for a predisposition to response to conspecifics put forward by Immelmann could be explained by hitherto uncontrolled differences in experience.

Animals↗
PubMed2005

Reverse genetic analyses of gamete-enriched genes revealed a novel regulator of the cAMP signaling pathway in Dictyostelium discoideum.

Sexual development in Dictyostelium discoideum is initiated by the fusion of opposite mating type cells to form zygote giant cells, which subsequently gather and phagocytose surrounding cells for nutrition to form macrocysts. Here we performed the targeting of 24 highly gamete-enriched genes we previously isolated, and successfully generated knockout mutants for 16 genes and RNAi mutants for 20 genes including 6 genes without disruptants. In the knockout mutants of two genes, cell aggregation toward the giant cells was much less extensive and many cells remained around poorly formed macrocysts. We named these genes tmcB and tmcC. Although macrocyst formation of wild type cells was suppressed by the addition of exogenous cAMP, that of knockout mutants of tmcB was much less sensitive. The mRNA level of phosphodiesterase (pde) was higher and that of its inhibitor (pdi) was lower in the latter cells compared to the parental strains during sexual development. Thus, tmcB appeared to be a novel regulator of the cAMP signaling pathway specific to sexual development. Knockout mutants of tmcC were indistinguishable from the wild type cells with respect to the cAMP response, suggesting that this gene is relevant to other processes.

Amino Acid Sequence↗
PubMed1998

Sexual maturation in male rhesus monkeys: importance of neonatal testosterone exposure and social rank.

In a 5-year longitudinal study, we examined the effect of disrupting the neonatal activity of the pituitary-testicular axis on the sexual development of male rhesus monkeys. Animals in a social group under natural lighting conditions were treated with a GnRH antagonist (antide), antide and androgen, or both vehicles, from birth until 4 months of age. In antide-treated neonates, serum LH and testosterone were near or below the limits of detection throughout the neonatal period. Antide + androgen-treated neonates had subnormal serum LH, but above normal testosterone concentrations during the treatment period. From 6 to 36 months of age, serum LH and testosterone were near or below the limits of detection. Ten of 12 control animals reached puberty during the breeding season of their 4th year, compared with five of 10 antide- and three of eight antide + androgen-treated animals. Although matriline rank was balanced across treatment groups at birth, a disruption within the social group during year 2 resulted in a marginally lower social ranking of the two treated groups compared with the controls. More high (78%) than low (22%) ranking animals reached puberty during year 4. During the breeding season of that year, serum LH, testosterone and testicular volume were positively correlated with social rank. Thus the lower social rank of treated animals may have contributed to the subnormal numbers of these animals reaching puberty during year 4. However, of those animals achieving puberty during year 4, the pattern of peripubertal changes in serum testosterone and testicular volume differed between control and antide-treated animals. The results appear to suggest that the disruption of normal activity of the neonatal pituitary--testicular axis retarded sexual development, but that social rank is a key regulatory factor in setting the timing of sexual maturation in male rhesus monkeys. The effect of neonatal treatment with antide and low social rank on sexual development could not be reversed by neonatal exposure to greater than normal concentrations of androgen.

Analysis of Variance↗
PubMed1990

Development and sexual maturation of Taenia crassiceps (Cestoda) in the golden hamster.

The development of cysticerci of Taenia crassiceps to mature tapeworms in the intestinal tract of cortisone-treated and untreated golden hamsters is described. The development of the worms in untreated hamsters is as follows. Maturation and branching of the uterus and the presence of ova in the uterus were observed on day 15 postinfection (PI). By day 21 PI, fertilization had taken place, as evidenced by the presence of sperm in the seminal receptacle. On day 28 PI, shelled eggs were observed in feces. The rate of development of the worms in cortisone-treated hamsters was similar to that observed in untreated hamsters. More worm recovery and a longer period of worm survival were seen in the cortisone-treated than in the untreated hamsters. Thus, both cortisone-treated and untreated golden hamsters can produce normal gravid individuals of T. crassiceps.

Animals↗
PubMed2002

Glial-neuronal-endothelial interactions are involved in the control of GnRH secretion.

In recent years compelling evidence has been provided that cell-cell interactions involving non-neuronal cells, such as glial and endothelial cells, are important in regulating the secretion of GnRH, the neuropeptide that controls both sexual development and adult reproductive function. Modification of the anatomical relationship that exist between GnRH nerve endings and glial cell processes in the external zone of the median eminence modulates the access of GnRH nerve terminals to the portal vasculature during the oestrous cycle. The establishment of direct neuro-haemal junctions between GnRH neuroendocrine terminals and the portal vasculature on the day of pro-oestrus may be critical for the transfer of GnRH upon its release into the fenestrated capillaries of the median eminence. Notwithstanding the importance of these plastic rearrangements, glial and endothelial cells also regulate GnRH neuronal function via specific cell-cell signalling molecules. While endothelial cells of the median eminence use nitric oxide to effect this regulatory control, astrocytes employ several growth factors, and in particular those of the EGF family and their erbB receptors to facilitate GnRH release during sexual development. Loss of function of each of these erbB receptors involved in the astroglial control of GnRH secretion leads to delayed sexual development. It is clear that regulation of GnRH secretion by cell-cell communication mechanisms other than transsynaptic inputs is an important component of the central neuroendocrine process controlling mammalian reproduction.

Animals↗
PubMedDate not supplied

GnRH and hCG tests in healthy adolescents and adults.

With the aim of obtaining reference values of GnRH test and of hCG test in a Venezuelan population, the authors evaluated the response of the pituitary LH and FSH to the GnRH action in 48 adolescents and 43 adults. Also, in 22 adolescents and in 22 adults from the same sample they evaluated the hCG effect on the gonadal steroids secretion. The maximum LH increment was obtained 30 min after GnRH stimulation, independently from the patients' age and their sexual development. FSH maximum increment was obtained 60 min after GnRH in the adults; meanwhile, the FSH maximum increment was obtained 30 min after GnRH stimulation in the Tanner stage 4 adolescents, and 90 min post-GnRH in the Tanner 5 adolescents. The gonadal steroid secretion 2, 24, 48, and 72 h post-hCG was significantly lower in the Tanner 4 adolescents. The gonadal steroid response post-hGC stimulation in the Tanner 5 adolescent group was similar to the one obtained in the adults. In late puberty the LH response to GnRH stimulus is not related either to age or to sexual development, contrary to the FSH response obtained after GnRH and the gonadal steroid response after hCG stimulus, both of which are related to age and patients' sexual development.

Adolescent↗
PubMed1998

Molecular genetics of mating recognition in basidiomycete fungi.

The recognition of compatible mating partners in the basidiomycete fungi requires the coordinated activities of two gene complexes defined as the mating-type genes. One complex encodes members of the homeobox family of transcription factors, which heterodimerize on mating to generate an active transcription regulator. The other complex encodes peptide pheromones and 7-transmembrane receptors that permit intercellular signalling. Remarkably, a single species may have many thousands of cross-compatible mating types because the mating-type genes are multiallelic. Different alleles of both sets of genes are necessary for mating compatibility, and they trigger the initial stages of sexual development--the formation of a specialized filamentous mycelium termed the dikaryon, in which the haploid nuclei remain closely associated in each cell but do not fuse. Three species have been taken as models to describe the molecular structure and organization of the mating-type loci and the genes sequestered within them: the pathogenic smut fungus Ustilago maydis and the mushrooms Coprinus cinereus and Schizophyllum commune. Topics addressed in this review are the roles of the mating-type gene products in regulating sexual development, the molecular basis for multiple mating types, and the molecular interactions that permit different allelic products of the mating type genes to be discriminated. Attention is drawn to the remarkable conservation in the mechanisms that regulate sexual development in basidiomycetes and unicellular ascomycete yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, a theme which is developed in the general conclusion to include the filamentous ascomycetes Neurospora crassa and Podospora anserina.

Amino Acid Sequence↗
PubMed2000

Glia-to-neuron signaling and the neuroendocrine control of female puberty.

It is becoming increasingly clear that astroglial cells are active participants in the process by which information is generated and disseminated within the central nervous system (CNS). In the hypothalamus, astrocytes regulate the secretory activity of neuroendocrine neurons. They contribute to facilitating sexual development by stimulating the release of luteinizing hormone-releasing hormone (LHRH), the neuropeptide that controls sexual development, from LHRH neurons. Astrocytes secrete several growth factors able to stimulate LHRH secretion. Two members of the epidermal growth factor (EGF) family--transforming growth factor alpha (TGFalpha) and the neuregulins (NRGs)-are produced in hypothalamic astrocytes and elicit LHRH secretion indirectly, via activation of receptor complexes formed by three members of the EGF receptor family, also located on astrocytes. Activation of these receptors results in the production of at least one neuroactive substance, prostaglandin E2 (PGE2), which stimulates LHRH secretion upon binding to specific receptors on LHRH neurons. Overexpression of TGFalpha in the hypothalamus accelerates puberty, whereas blockade of either TGFalpha or NRG actions delays the process, indicating that both peptides are physiological components of the neuroendocrine mechanism that controls sexual maturation. An increase in hypothalamic expression of at least two of the erbB receptors is initiated before the pubertal augmentation of gonadal steroid secretion and is completed on the day of the first preovulatory surge of gonadotropins. This secondary increase is brought about by gonadal steroids. Estrogen and progesterone facilitate erbB-mediated glia-to-LHRH neuron communication by enhancing astrocytic gene expression of at least one of the EGF-related ligands (TGFalpha) and two of the receptors (erbB-2 and erbB-4). They also facilitate the LHRH response to PGE2 via induction of PGE2 receptors in LHRH neurons. A search for genes that may act as upstream regulators of the pubertal process resulted in the identification of two potential candidates: Oct-2, a POU domain gene originally described in cells of the immune system, and TTF-1, a member of the Nkx family of homeodomain transcriptional regulators required for diencephalic morphogenesis. The hypothalamic expression of both genes increases during juvenile development before the first hormonal manifestations of puberty take place. Their mRNA transcripts are localized to specific hypothalamic cellular subsets, where they appear to regulate different, but interactive, components of the neuronal-glial complex controlling LHRH secretion. While Oct-2 transactivates the TGFalpha promoter, TTF-1 does so to the erbB-2 and LHRH genes but inhibits preproenkephalin promoter activity, suggesting that both transcriptional regulators may act coordinately in the normal hypothalamus to activate genes involved in facilitating the advent of puberty and repress those restraining sexual development. Altogether, these observations indicate that the central activation of the pubertal process involves the participation of both neuronal and astroglial networks and the contribution of upstream transcriptional regulators acting on both the neuronal and glial components of the system.

Animals↗
PubMed1984

Developmental changes in the diurnal rhythm of secretion of corticosterone and LH in the domestic hen.

When diurnal changes in the plasma concentrations of corticosterone and LH were compared at various times during sexual development a diurnal rhythm in the secretion of corticosterone was most pronounced at 4.5 weeks of age in hens maintained on a schedule of 8 h light: 16 h darkness (8L: 16D) and at 8.5 weeks of age in hens maintained on 16L: 8D. At these ages the phase-angle of the rhythm in relation to the onset of darkness was 3 h earlier than had been observed in previous studies of the adult hen. The characteristics of the corticosterone rhythm changed during sexual development and diurnal changes were no longer evident in hens at 17 weeks of age at a time when prepubertal plasma concentrations of LH were maximal. However, there was a tendency for plasma concentrations of corticosterone to fluctuate diurnally in hens studied at less than 10 days before the onset of lay although not to the same extent as has previously been observed in the adult hen. This period of development was associated with a pronounced increase in the plasma concentration of progesterone. An increase in the plasma concentration of LH at the onset of darkness was observed at all ages in hens maintained on either photoschedule . In hens of 4.5-15 weeks of age maintained on 16L: 8D or 8L: 16D this increase in the plasma concentration of LH was sustained during the first 5 or 8-11 h of darkness respectively but at 17 weeks of age only a transient increase in LH was seen at the onset of darkness. Plasma concentrations of LH in samples of plasma taken at intervals of between 3 days and 2 weeks throughout sexual development were, until 18-19 weeks, consistently higher in hens maintained on a photoschedule of 16L: 8D than on 8L: 16D.

Animals↗
PubMed2004

Expression of prolactin receptor mRNA in the abdominal gland of the newt Cynops ensicauda.

To further the understanding that the structural development of the Cynops ensicauda abdominal gland and the synthesis of the pheromone silefrin in the gland are under the control of prolactin and androgen, we sought to demonstrate the presence of prolactin receptor (PRLR) mRNA in the gland. Firstly, PRLR cDNA was isolated from an abdominal gland cDNA library. A cDNA consisting of a 415-bp 5'-untranslated region, 1878-bp open reading frame and 175-bp 3'-untranslated region was obtained. The deduced amino acid sequence consisted of 626 amino acids with signal peptide and single transmembrane domain. By Northern blot analysis using partial C. ensicauda PRLR cDNA, two transcripts, of 3 and 10 kb, were detected for PRLR in the brain, liver, kidney, abdominal gland, oviduct and skin. RT-PCR coupled with Southern blot analysis showed that the PRLR gene was transcribed broadly in newt organs and revealed that PRLR mRNA levels in the abdominal gland were much higher in sexually developed newts than in the sexually undeveloped ones. By in situ hybridization, specific signals were detected in the epithelial cells of the abdominal gland of sexually developed newts, but much less in those of the sexually undeveloped ones.

3' Untranslated Regions↗