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Characterization of the Prr1 response regulator with special reference to sexual development in Schizosaccharomyces pombe.

The histidine (His)-to-Aspartate (Asp) phosphorelay is a paradigm of intracellular signaling systems through protein phosphorylation in both prokaryotes and eukaryotes. The fission yeast Schizosaccharomyces pombe has three histidine kinases (Phk1/Mak2, Phk2/Mak3, and Phk3/Mak1), together with two response regulators (Mcs4 and Prr1). The results of recent extensive studies suggested that these His-to-Asp phosphorelay components are involved in oxidative stress responses through the transcriptional regulation of several scavenger genes for toxic free radicals. It was also suggested that they were somehow implicated in control of both the mitotic and meiotic cell proliferations. Among these S. pombe His-to-Asp phosphorelay components, however, the function of Prr1 is less clear. We here characterized a mutant, named prr1-D418N, specifying an altered Prr1 protein that presumably acts as a gain-of-function (or constitutive-active) mutant, with special reference to sexual development. The mutant cells showed a striking phenotype in that they underwent mating even in a nitrogen-sufficient medium, under which conditions the wild-type cells hardly did so. Furthermore, the mutant cells underwent mating very rapidly in a nitrogen-deficient medium. Under anaerobic (or micro-aerobic) growth conditions, the wild-type cells were not capable of undergoing sexual development even in a nitrogen-deficient medium. The prr1-D418N cells underwent mating efficiently under such anaerobic growth conditions. Taken these together, it was suggested that the function of Prr1 is closely linked to the well-characterized signaling pathways for induction of the sexual development, in a way that this response regulator regulates a critical step of the initiation of meiosis through activating the transcription of ste11+, mam2+, and mei2+, in S. pombe.

Amino Acid Substitution↗

Sexual development of dairy bulls in the Mexican tropics.

Sexual development and pubertal traits were studied in Holstein Frisian (Ho) and Brown Swiss (BS) bulls born and maintained under tropical conditions. Characteristics evaluated every 2 weeks, from 27 to 63 weeks of age, included live weight, scrotal circumference, testicular diameter, semen quality and sexual behavior. Puberty was defined as the age at which a bull first produced an ejaculate containing at least 50 x 106 spermatozoa, with a minimum of 10% progressive motility. Testicular growth was linear in Ho bulls and quadratic in BS bulls. There was no breed difference in age at puberty (Ho, 333 +/- 15.8 days; BS, 311 +/- 10.5 days). However, at puberty, live weight and scrotal circumference tended to be greater in Ho (276 +/- 16.9 kg and 28.4 +/- 1 cm, respectively) than in BS bulls (233 +/- 11.3 kg and 25.9 +/- 0.7 cm, respectively), and testicular diameter was larger for Ho (5.5 +/- 0.24 cm) than for BS bulls (4.8 +/- 0.16 cm). Pooled data for all bulls for semen characteristics at puberty were: volume, 6.3 +/- 0.6 ml; progressive motility, 26.8 +/- 4.4%; sperm concentration, 58.5 +/- 13.9 x 10(6) spermatozoa/ml, and 351.5 +/- 91.2 x 10(6) spermatozoa/ejaculate. These values improved until at least 18 weeks after puberty. Eighty-five percent of bulls mounted heifers by 206 days of age, but only a few bulls had mounts with ejaculation during the study. It was concluded that reproductive development was similar between Ho and BS bulls, but slower than that reported for dairy bulls in temperate areas. Variation in some characteristics, such as scrotal circumference, was observed among bulls within each breed group, which might be of benefit for genetic selection.

Aging↗

Sleep-associated gonadotrophin and oestradiol patterns in girls with precocious sexual development.

Circulating concentrations of gonadotrophins and oestradiol (E2) during sleep were examined in six girls aged 5-10 years with precocious sexual development. All subjects exhibited nocturnal increments of LH and/or FSH. Gonadotrophin secretion appeared to vary from pulsatile release to random oscillations. Three subjects with LH pulses of greater than 5 miu/ml and a concomitant FSH rise had a temporal elevation of E2 during sleep. The other three subjects with pulses of either LH or FSH of less than 5 miu/ml had no nocturnal rise in E2. These data suggest that the nocturnal elevation of E2 results from pituitary release of both LH and FSH, leads to premature sexual development, and may be occasioned by inappropriate timing of hypothalamic gonadotrophin-releasing hormone (LHRH) secretion.

Child↗

Effects of indole and caffeine on cAMP in the ind1 and cfn1 mutant strains of Schizophyllum commune during sexual development.

The ind1 and cfn1 mutations of Schizophyllum commune express resistance to high concentrations of indole and caffeine respectively, and also affect sexual development. To clarify molecular events caused by the mutations, it was investigated how cAMP levels in S. commune strains respond to externally supplied indole and caffeine. Both compounds increased the cAMP levels in wild-type strains under several culture conditions. During sexual development of the ind1 mutant, the cAMP level in an early stage (hyphal aggregation) was highly increased by addition of indole, and the phenomenon disappeared in a later stage (fruit body formation). For the cfn1 mutants, the incremental increase in cAMP levels by addition of caffeine was smaller than that of wild-type strains.

Caffeine↗

[The genes in the molecular cascade of the mammalian sexual development].

The sex of an individual is established as a consequence of molecular events that occur in the complex genetic cascade. During sexual development, morphological changes are closely associated with the action of genes expression of which is tightly regulated according to the genetic program. Recently, a number of genes that are involved in this process have been isolated. WT-1 and SF-1 are required for the early formation of the gonadal primordium. SRY is the switch to start the male sexual differentiation by triggering the Sertoli cell lineage. An autosomal gene SOX9, which can cause the sex reversal, might also be involved in the male sex determination. SF-1 is a key factor for the male sexual differentiation, regulating the expression of MIS and the synthesis of testosterone in the fetal testis. DAX1 might be responsible for the female sexual development. The mutation or abnormal expression of these regulatory genes and their downstream genes can cause a variety types of the sex reversal and/or malformation of the gonad and the internal and external genitalia.

Animals↗

Sexual development in beef bulls following zeranol implants.

Two trials were conducted to study the effect of zeranol implants on growth and sexual development of bull calves. Trial 1 compared the effects of implanting with 72 mg of zeranol at 48 d of age (branding), at 215 d of age, or at both times with nonimplanted control bulls. Implanting at branding resulted in decreased scrotal circumference, testicle weight and proportion of bulls that could produce an ejaculate at 14 mo of age (P less than .01). Implanting at 215 d of age had no effect on any of these traits. Growth rate was not increased by implanting at either time but was decreased (P less than .02) in animals implanted at both times when compared with control bulls. In trial 2, both bulls and steers were implanted with zeranol and compared with nonimplanted control bulls and steers. Thirty-six-milligram implants were given at 21, 103, 260 and 343 d of age. Scrotal circumference, testicle weight and serum testosterone concentrations decreased (P less than .01) and the occurrence of penis abnormalities increased (P less than .01) in implanted bulls compared with control bulls. By the time of slaughter, however, testosterone concentrations were equal in control and implanted bulls; and the difference in scrotal circumference was diminishing. This is interpreted as evidence that as the bulls get older, they can overcome the effect of the implants. Carcass weights were heavier in implanted steers than in control steers but were lighter in implanted bulls than in control bulls (P less than .02). Carcasses of implanted bulls had higher quality scores and more marbling than control bulls, but carcasses of implanted steers had lower quality scores and less marbling than control steers (both interactions, P less than .01). Implanting bulls with zeranol at an early age resulted in restricted sexual development but not in total sterility. Repeated zeranol implants throughout the growing and finishing phase enhanced carcass quality in bulls slaughtered at 14 to 16 mo of age.

Animals↗

Roles of Wee1 and Nim1 protein kinases in regulating the switch from mitotic division to sexual development in Schizosaccharomyces pombe.

In self-fertile strains of the fission yeast Schizosaccharomyces pombe, nitrogen starvation initiates a program of sexual development in which cells express mating pheromones and receptors, arrest cell cycle progression in G1, and conjugate. This process is dependent on Rum1, an inhibitor of the Cdc2-Cdc13 and Cdc2-Cig2 cyclin B kinases. The M-phase induction activity of Cdc2-Cdc13 is inhibited by Wee1 tyrosine kinase, which phosphorylates Cdc2 on tyrosine-15. We report here that Wee1 activity is also important for mating. This discovery arose from studies of Nim1, a kinase which promotes mitosis by inhibiting Wee1. Nim1 was previously thought to have an important role in promoting mitosis during nitrogen starvation, but our studies revealed that Nim1 protein drops to an undetectable level within 15 min of nitrogen depletion. In contrast, Wee1 remains abundant, and tyrosine-phosphorylated Cdc2 is detected for at least 4 h after resuspension of cells in nitrogen-free medium. This suggested that maintenance of Wee1 activity may be important during the early stages of nitrogen starvation, a proposal confirmed by the observation that mating efficiency is reduced ca. fivefold in wee1- cells. Transcriptional induction of genes encoding mating factors and receptors is also delayed in wee1- cells. The wee1- mating defect is suppressed by deletion of cig2+, which encodes a B-type cyclin that promotes the onset of S and inhibits conjugation. These findings indicate that Wee1 and Rum1 act jointly to inhibit Cdc2 and promote sexual development in nitrogen-starved cells.

Ammonium Chloride↗

Genotype x environment interactions involving proportion of Brahman breeding and season of birth. II. Postweaning growth, sexual development and reproductive performance of heifers.

Postweaning growth, sexual development and reproductive traits were evaluated over a 3-yr period on 201 spring-born and 180 fall-born crossbred heifers with 0, 1/4 or 1/2 Brahman breeding. The proportion of Brahman breeding X season of birth interaction was significant for five traits (average daily gain weaning to yearling, yearling condition score, percentage of heifers detected in estrus, prebreeding condition score and percentage of heifers that became pregnant) and was not significant for six traits (yearling weight, hip height and conformation score, age and weight at puberty and prebreeding weight. Among spring-born heifers, 1/4 and 1/2 Brahman heifers outgained (P less than .05) 0 Brahman heifers from weaning to yearling by 50 and 66 g/d, respectively; among fall-born heifers, 1/4 and 1/2 Brahman heifers outgained (P less than .05) 0 Brahman heifers by 41 and 104 g/d, respectively. Yearling weight of 1/2 Brahman heifers was 13 and 10 kg heavier (P less than .05), respectively, than 0 and 1/4 Brahman heifers. Yearling hip height of 1/4 and 1/2 Brahman heifers were 1.9 and 5.7 cm taller (P less than .05), respectively, than 0 Brahman heifers. Weight prior to the start of the breeding season were similar among crossbred heifer groups and spring-born heifers were 66 kg heavier (P less than .05) than fall-born heifers. The percentage of heifers that became pregnant was similar among spring-born crossbred heifer groups, whereas among fall-born heifer groups 1/4 and 1/2 Brahman heifers were 25.2 and 49.4 percentage points lower (P less than .05), respectively, than 0 Brahman heifers.

Animals↗

Genetic analysis of the sam mutations, which induce sexual development with no requirement for nutritional starvation in fission yeast.

The cAMP pathway and the Ras pathway are the two major pathways to sexual development in the fission yeast Schizosaccharomyces pombe. To understand the cAMP pathway or the related pathway, we analyzed mutants that display a phenotype similar to cyr1-, that is, hyper-sporulation. Nine mutants termed sam (sporulation abnormal mutant), which are highly inclined to sexual development despite the presence of nitrogen sources, were partially characterized. Cyclic AMP was detected in all nine sam mutant cells, and over-expression of the adenylyl cyclase gene (cyr1) failed to suppress the hyper-sporulation phenotype of these sam mutants, suggesting that none of the sam mutants were likely to be allelic to cyr1. Epistatic tests of sam mutants showed that they were divided into two dominant and seven recessive mutants. Dominants were able to make spores in sam/sam+ heterodiploid cells upon abundant nutrients. Both two dominant mutants bypassed the inability to make spores in ras1 deficient diploid cells, suppressed the deficiency to execute sporulation in byr2 deficient diploid cells, but failed to suppress the byr1 deficiency. Two dominant mutations seem not to occur within the byr2 gene.

Base Sequence↗

An asexual fungus has the potential for sexual development.

The availability of cloned genes that control sexual reproduction (mating type genes) in high fungi has allowed us to consider the causes of failure to mate in asexual fungi. We report here that the asexual fungus Bipolaris sacchari has a homolog of the MAT-2 gene of its sexual ascomycete relative Cochliobolus heterostrophus. The B. sacchari MAT-2 sequence is highly similar to that of C. heterostrophus MAT-2 and, in fact, functions in transgenic C. heterostrophus. Thus, the asexual nature of B. sacchari is not due to absence or mutation of MAT. When either of the C. heterostrophus MAT genes was transformed into B. sacchari, the recipient could neither self nor cross with other B. sacchari strains, in contrast to transgenic C. heterostrophus strains which can do both. Persistent asexuality of B. sacchari, in spite of the presence of complementary functional MAT genes, suggests that this fungus lacks genes other than MAT which are essential for mating. Notably, the transgenic B. sacchari strains were sometimes able to initiate, but not complete, sexual development in interspecific pairings with C. heterostrophus. Transcript analysis showed that the B. sacchari MAT-2 gene is expressed in transgenic C. heterostrophus and that the C. heterostrophus MAT genes are expressed in transgenic B. sacchari. No transcript of the native B. sacchari MAT-2 gene was detected under any growth condition tested.

Amino Acid Sequence↗

Cellular localization of steroid hormone-regulated proteins during sexual development in Achlya.

In the fungus Achlya ambisexualis sexual development in the male strain E87 is controlled by the steroid hormone antheridiol. To investigate the effects of antheridiol on the synthesis and/or accumulation of specific cellular proteins we have analysed [35S]methionine-labeled proteins from control and hormone-treated cells using both one-dimensional (1D) and two-dimensional (2D) PAGE. Since in a total cell extract, hormone-induced changes in specific proteins might not be apparent against a background of more abundant proteins, cells were fractionated prior to protein isolation. It was also necessary to establish a concentration of hormone carrier, in this case methanol, which by itself did not alter the pattern of protein synthesis. Using these approaches the addition of the hormone antheridiol to vegetatively growing cells of Achlya E87 was found to result in changes in the synthesis and/or accumulation of at least 16 specific proteins, which could be localized to the cytoplasmic, nuclear or cell wall/cell membrane fractions. The most prominent changes observed in the hormone-treated cells included the appearance in the cytoplasmic fraction of labeled proteins at 28.4 and 24.3 kD which were not detectable in control cells, and a significant enrichment in the labeling of a 24.3 kD protein in the cell wall/cell membrane fraction. A marked increase in the labeling of 85, 63 and 47 kD proteins in the nuclear fraction from hormone-treated cells was also noted. The molecular weight (MW) and the behavior on 2D gels of the 85 kD hormone-induced protein appeared very similar to that of the 85 kD heat-shock protein reported in Achlya. Quantitive changes in the [35S]methionine labeling of several other proteins were noted in all three cell fractions.

Cell Compartmentation↗

Pediatric sexuality: promoting normal sexual development in children.

Since the sexual revolution of the 1960s there has been an openness regarding sexual exploration that has resulted in an increase of sexually transmitted diseases and teenage pregnancies. Clinicians can mitigate the unhealthy results of such exploration through a therapeutic relationship with their patients. This article provides practical ways to approach and educate the pediatric patient and parent regarding normal sexual growth and development and the promotion of healthy, responsible sexual behavior. Using developmental theories as a foundation, sexuality is examined from birth through the adolescent years.

Adolescent↗

Variations in internet-related problems and psychosocial functioning in online sexual activities: implications for social and sexual development of young adults.

This survey of 760 university students examined differences in Internet-related problems and psychosocial functioning between four patterns of participation in online sexual information and entertainment activities. Students who did not participate in either online sexual activity were more satisfied with their offline life and more connected to friends and family. Those who engaged in both online sexual activities were more dependent on the Internet and reported lower offline functioning. Students who only sought sexual information maintained strong offline affiliations. Those who only sought entertainment did not report lower offline functioning. Respondents most deficient in offline social support did not report compensatory online support. Despite students' common participation in online sexual activities (OSA) as a venue for social and sexual development, those relying on the Internet and the affiliations it provides appear at risk of decreased social integration. The authors discussed the finding's implications for social and sexual development.

Adult↗

The significance of diagnostic laparotomy in girls with disorders of sexual development.

Chromosomal analyses were performed in 5 patients from 13 days to 16 years of age to clarify intersexual genitalia, disorders of secondary sexual development and growth retardation. Laparotomies were felt to be indicated because of discrepancies in the results of chromosoma analyses, clinical picture and endocrinologic findings. Among others, pure gonadal dysgenesis was found in a patient with karyotype 46 XX, functional ovaries in a chromosomal Turner's syndrome and a Müllerian anlage with two dysgenetic testes in a 45 X/46 XY mosaic. Since gonads with one cell line containing Y-chromosomes carry a high danger of malignant change, they should be removed as early as possible. It is known that disorders of sexual development can be caused by many and various anomalies of the sex chromosomes. Cooperation among endocrinologists, human geneticists and pediatric surgeons is essential for clarification of the diagnosis.

Adolescent↗

Effects of gabaergic and serotoninergic systems on hypothalamic content of catecholamines during sexual development in female rats.

OBJECTIVES: The aim of the present investigation was to determine whether the catecholaminergic system is involved in gabaergic and serotoninergic effects on gonadotrophin secretion during sexual development. To this end, we studied the effect of GABAergic and serotoninergic systems on hypothalamic catecholamine content at different stages of sexual development. METHODS: The effect of GABA A and GABA B agonists and 5-hydroxy-L-tryptophan on hypothalamic noradrenaline and dopamine content were determined in prepubertal (16 days old) and peripubertal (30 days old) rats. RESULTS: At 16 days of age GABA agonists did not modify hypothalamic noradrenaline content, whereas a significant decrease in catecholamine concentration was observed in peripubertal rats at 30 days of age. Similar changes were observed with GABA agonists administration on dopamine hypothalamic levels, i.e no effects at 15 days of age and a significant decrease at 30 days. The administration of 5-hydroxy-l-tryptophan (5-HTP) induced a decrease of hypothalamic concentration of noradrenaline and dopamine at both ages. CONCLUSION: Results indicate that the GABAergic system modifies the hypothalamic catecholamine content in peripubertal but not in prepubertal rats while serotonin has an inhibitory effect at both stages of sexual maturation. Even though both systems induce similar ontogenic modifications on the gonadotrophin axis (stimulatory effect in prepubertal and inhibitory action in peripubertal and adult rats) the present results appear to indicate that GABAergic and serotoninergic systems regulate gonadotrophin secretion by different hypothalamic mechanisms.

Animals↗

Effects of peripubertal exposure to triphenyltin on female sexual development of the rat.

Triphenyltin (TPT) belongs to the group of organotin compounds which have been shown to affect reproduction in mammals. It is used as a fungicide and antifouling agent and the main source of human exposure is via food. We studied the effects of 2 or 6 mg TPT/kg bw on female sexual development using a modification of the Rodent 20-Day Thyroid/Pubertal Female Assay. Moreover, the effect of TPT before the onset of puberty was investigated. Beginning at postnatal day (PND) 23 female Wistar rats were treated per gavage until either PND 33 or the first estrus after PND 53. A delay in the completion of vaginal opening (VO) was observed in the 6 mg TPT group, while the 2mg TPT group showed advanced VO. Significantly increased ovarian weights were observed in both treatment groups. Steroid hormone levels and ovarian aromatase activity were affected after exposure to 6 mg TPT/kg bw, while treatment with 2mg TPT/kg bw resulted in minor changes of these endpoints. We conclude that peripubertal exposure to 6 mg TPT/kg bw, and to a lesser extent to 2mg TPT/kg bw, affects female sexual development.

Animals↗

Neuregulins signaling via a glial erbB-2-erbB-4 receptor complex contribute to the neuroendocrine control of mammalian sexual development.

Activation of erbB-1 receptors by glial TGFalpha has been shown to be a component of the developmental program by which the neuroendocrine brain controls mammalian sexual development. The participation of other members of the erbB family may be required, however, for full signaling capacity. Here, we show that activation of astrocytic erbB-2/erbB-4 receptors plays a significant role in the process by which the hypothalamus controls the advent of mammalian sexual maturation. Hypothalamic astrocytes express both the erbB-2 and erbB-4 genes, but no erbB-3, and respond to neuregulins (NRGs) by releasing prostaglandin E(2) (PGE(2)), which acts on neurosecretory neurons to stimulate secretion of luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual development. The actions of TGFalpha and NRGs in glia are synergistic and involve recruitment of erbB-2 as a coreceptor, via erbB-1 and erbB-4, respectively. Hypothalamic expression of both erbB-2 and erbB-4 increases first in a gonad-independent manner before the onset of puberty, and then, at the time of puberty, in a sex steroid-dependent manner. Disruption of erbB-2 synthesis in hypothalamic astrocytes by treatment with an antisense oligodeoxynucleotide inhibited the astrocytic response to NRGs and, to a lesser extent, that to TGFalpha and blocked the erbB-dependent, glia-mediated, stimulation of LHRH release. Intracerebral administration of the oligodeoxynucleotide to developing animals delayed the initiation of puberty. Thus, activation of the erbB-2-erbB-4 receptor complex appears to be a critical component of the signaling process by which astrocytes facilitate the acquisition of female reproductive capacity in mammals.

Animals↗

Androgenic and estrogenic effects of the synthetic androgen 17alpha-methyltestosterone on sexual development and reproductive performance in the fathead minnow (Pimephales promelas) determined using the gonadal recrudescence assay.

The effects of the androgen, 17alpha-methyltestosterone were assessed on sexual development and reproductive performance in the fathead minnow (Pimephales promelas) using a gonadal recrudescence assay. In this assay, mature male and female fathead minnow, previously kept under simulated winter conditions (15 degrees C; 8:16 h light:dark regime) were transferred to simulated summer conditions (25 degrees C water temperature; 16:8 h light:dark regime) to induce gonadal recrudescence. To assess sexual development fish were exposed to nominal concentrations of 0, 0.1, 1, 5 and 50 microg/L 17alpha-methyltestosterone. After 3 weeks of chemical exposure, effects on condition (condition factor, CF), plasma vitellogenin (VTG), secondary sex characteristics, gonad growth (gonadosomatic index; GSI) and gonad histology were investigated. Reproductive performance, including reproductive output (egg production), spawning behaviour, and fertilisation rate were measured over a subsequent 3-week-period in breeding adults maintained in clean water. 17alpha-Methyltestosterone had no effects on the condition of fish at any of the doses tested. 17alpha-Methyltestosterone induced both androgenic and estrogenic effects with females generally more affected by 17alpha-methyltestosterone than males: atretic follicles and male-specific sex characteristics (androgenic effect) were induced in females at > or = 0.1 and > or = 1 microg/L 17alpha-methyltestosterone, respectively. An inhibitory effect on ovary growth occurred at an exposure concentration of 50 microg/L 17alpha-methyltestosterone. In males 1 microg/L 17alpha-methyltestosterone induced a concentration-response induction of plasma vitellogenin (estrogenic effect) likely due to its conversion into 17alpha-methylestradiol, rather to the competition with endogenous steroids and their cross reactivity with the estrogen receptor. In the fish breeding studies, concentration-dependent reductions in egg number, fertilisation rate and increases in abnormal sexual behaviour in females were observed. All of these effects occurred at exposure concentrations of > or = 5 microg/L 17alpha-methyltestosterone. Thus, it could be assumed that the observed estrogenic effects in male fathead minnow were likely to the conversion of 17alpha-methyltestosterone into the estrogen 17alpha-methylestradiol, rather to the acting of 17alpha-methyltestosterone itself. In conclusion to this, showing hormonally activity of 17alpha-methyltestosterone in fish down to 100 ng/L, indicates that its potency was close to the range of several naturally occurring estrogens.

Analysis of Variance↗