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Self-examination of the genital area is an important technique to teach adolescent males. It facilitates early detection of testicular cancer and permits prompt recognition of venereal lesions. The general physical examination enables the physician to assess the stage of sexual development, detect any genital abnormalities and instruct the adolescent in the self-examination technique.
Renal transplantation is the best form of renal replacement therapy for children reaching end-stage renal failure. The first human transplantation was performed by Dr. Voronoy from a cadaver donor in 1933; however, because of the lack of immunological laboratory assessments, this transplantation resulted in rejection. Progress in immunological evaluation and new immunosuppressive drugs have improved survival in renal transplantation. The first renal transplantation in Turkey was performed by Dr. Haberal et al. on November 3, 1975. This child was one of five siblings with juvenile nephronophytisis, and the mother was the donor. Dr. Haberal has thus pioneered renal transplantation in Turkey. In the following years Dr. Haberal initiated cadavral transplantation in our country in collaboration with Eurotransplant. He has also contributed to the law concerning transplantation in Turkey. Subsequently many transplantation centers have been developed in the country. In spite of marked progress in transplantation technology, pediatric transplantation has not improved as fast as adult transplantation. This is due to several factors, such as the difference in the etiological factors leading to chronic renal failure, technical factors, growth and sexual development, factors relevant to infections and vaccinations, and psychological problems.
Female rat dams, housed in 12L:12D photoperiod, were pinealectomized or injected daily 1(1/2) h before onset of darkness with 250 mg melatonin/100 g BW., during pregnancy; control and pinealectomized dams received a placebo. Somatic, reproductive organs and gonadotropins levels luteinizing hormone (LH) and follicle stimulating hormone (FSH) of male offspring were examined at the following phases of their sexual development: neonate, infantile, juvenile or prepubertal and pubertal periods. Pinealectomy of the mother produced an altered developmental pattern in the offspring (PIN-X offspring). During the infantile period when pups are lacking maternal melatonin and their own melatonin rhythm is not yet established, a delayed growth of body and testis weights was observed. After the second week of life, from 15 to 25 days of age, coinciding with the initiation of the melatonin rhythm, a speed-up growth of body and testes was observed, followed by a delayed growth from 25 to 30 days, in the juvenile period; this also coinciding with reduced LH levels observed at 30 days of age. Indeed, in PIN-X offspring significantly greater growth rate was observed during the pubertal period than in control offspring, which could be due to the increase in LH secretion up to normal values observed in the PIN-X offspring. Seminal vesicles of the PIN-X offspring also showed delayed growth, which was overcome at the pubertal period. Melatonin (MEL) treatment during pregnancy produced minor alterations in postnatal development of the reproductive tract. Only increased pituitary gland weight was observed at 15 and decreased at 25 days of age. At 25 days of age, MEL offspring reached the highest LH values, and at 30 days of age, PIN-X offspring still show low values. Which suggests that other factors than the endocrine activity of the gland are affecting the somatic growth of the pituitary gland. Seminal vesicles weight was delayed at 25 days of age in the MEL offspring. These results indicate that maternal melatonin is necessary for a normal somatic growth and postnatal development of reproductive organs of the offspring.
Two studies were conducted to determine the consequences of extended treatment with estradiol or testosterone on sexual behavior in postpubertal, female pigs. After ovariectomy, either steroid was administered for 6 weeks at dosages sufficient to maintain serum concentrations similar to those observed in mature male pigs. Behavioral evaluations were initiated 2 months after the last steroid treatment. These treatments reduced receptivity (immobile stance when placed with a mature male) and proceptivity (preference to remain near a mature male) in association with an increase in aggressive behavior. In females treated previously with both estradiol and progesterone, sexual behaviors 2 months later were similar to those of control females. When evaluations were repeated 5 months after extended estradiol treatment had ceased, receptivity and proceptivity had returned to that of control pigs and aggressive behavior had diminished greatly. Interpretation of these changes in behavior is that extended periods of estradiol or testosterone treatment sustain activational influences for a considerable amount of time after treatments cease and progesterone antagonizes estradiol's effect on these behaviors. In a companion study, pubertal and post-pubertal females were similar for receptivity but pubertal females spent less time near a mature male. This difference in proceptivity likely reflects a maturational change associated with sexual development in female pigs. Collectively, these observations in postpubertal, female pigs document that prolonged estrogen treatment will activate aggressive behaviors in association with reduced proceptivity and receptivity. Because these behavioral changes are reversible by 5 months after cessation of treatment, they are not the result of sexual differentiation.
The study which was conducted in 1990 in Berlin, Germany, compares two samples of 542 adolescents from West Berlin and 340 from East Berlin. The present investigation shows that the general trend toward sexual liberality among adolescents is continuing and that necessary processes of adolescent sexual development appear not to be influenced by the threat of AIDS. Though the level of knowledge about the threat of AIDS is, on the whole, satisfactory, this does not in itself guarantee determined and consistent AIDS-preventive behavior. Fewer than one-third of sexually-active adolescents, and even fewer than one-fourth of those in the most sexually-active group, can be described as consistent users of condoms. The attitudes of adolescents in regard to contraceptive characteristics only partly suggest a preference for condoms. When adolescents are asked directly about condoms, they additionally emphasize their effect of reducing feeling and pleasure. Adolescents with experience of sexual intercourse rate condoms more negatively than do those without such experience. However, AIDS-education efforts can make use of the fact that consistent condom-users expressed clearly more positive attitudes to condoms than did others. Although the comparison between East and West Berlin adolescents yielded differences in certain details, these differences are not of significance to AIDS-education programs which seek to increase AIDS-preventive behavior.
HIT (histidine triad) proteins, named for a motif related to the sequence HphiHphiHphiphi (phi, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides, and contain a approximately 30 kDa domain that is typically either a homodimer of approximately 15 kDa polypeptides with two active-sites or an internally, imperfectly repeated polypeptide that retains a single HIT active site. On the basis of sequence, substrate specificity, structure, evolution, and mechanism, HIT proteins can be classified into the Hint branch, which consists of adenosine 5'-monophosphoramide hydrolases, the Fhit branch, which consists of diadenosine polyphosphate hydrolases, and the GalT branch, which consists of specific nucleoside monophosphate transferases, including galactose-1-phosphate uridylyltransferase, diadenosine tetraphosphate phosphorylase, and adenylyl sulfate:phosphate adenylytransferase. At least one human representative of each branch is lost in human diseases. Aprataxin, a Hint branch hydrolase, is mutated in ataxia-oculomotor apraxia syndrome. Fhit is lost early in the development of many epithelially derived tumors. GalT is deficient in galactosemia. Additionally, ASW is an avian Hint family member that has evolved to have unusual gene expression properties and the complete loss of its nucleotide binding site. The potential roles of ASW and Hint in avian sexual development are discussed elsewhere. Here we review what is known about biological activities of HIT proteins, the structural and biochemical bases for their functions, and propose a new enzyme mechanism for Hint and Fhit that may account for the differences between HIT hydrolases and transferases.
Progestogen-only minipills and other systems for releasing low doses of progestogens alone are widely used for contraception in breast-feeding women around the world. There is good evidence to confirm their acceptability and their lack of effect on milk production, neonatal growth and early development. In contrast, combined oral contraceptives frequently decrease milk production, and may produce minor changes in milk composition. However, even combined oral contraceptives do not appear to produce adverse effects on neonatal well-being and development, although minor reductions in initial growth rate may sometimes occur. Progestogen-only methods may also produce subtle changes in milk composition, although less than combined oral contraceptives. Steroids are transferred from plasma into milk in small quantities, but the amounts are usually very low or insufficient to allow detection in the infants using present-day assays. There has been theoretical concern that these tiny amounts of steroids might affect neonatal reproductive development, but this appears to be unwarranted. Progestogen-only methods are being widely used for post-partum contraception, and they appear to have particular advantages in this situation. They also have few disadvantages; a theoretical concern about a possible effect on later reproductive or sexual development has no evidence to support it. The present licensing situation in Australia, which lists lactation as a relative contraindication to progestogen-only contraceptive use, causes real concern to potential users and appears to lead to frequent errors in compliance.
The endocrine function of the mammalian pituitary-gonadal axis begins in utero. This is important particularly for the ontogeny and function of the male reproductive organs, the induction of which is critically dependent on the two fetal testicular hormones, testosterone and anti-müllerian hormone. In contrast, ovarian endocrine activity begins only after birth. The earliest phases of testicular hormone production are probably under autocrine or paracrine regulation, but the dependence on gonadotrophins starts in fetal life. During maturation of the hypothalamic-pituitary-testicular axis, the target organs acquire their responsiveness (viz receptors) before the onset of secretion of the tropic hormonal stimulus. The last link to develop is the feedback regulation, and the whole axis is functional in the developing male rat during the last days of gestation. Although gonadotrophin secretion starts in both sexes simultaneously, the fetal ovary is endocrinologically quiescent--its gonadotrophin responsiveness and endocrine activity begin only after birth. The fetal and postnatal periods of testicular activity have crucial effects on male sexual differentiation, whereas in the female, early sexual development occurs autonomously without influence of ovarian function. The purpose of this review is to elucidate some of the recent findings on the molecular mechanisms involved in the perinatal maturation of the rat hypothalamic-pituitary-gonadal axis.
We have recently described a female patient with myotubular myopathy (MTM1) and an interstitial deletion at Xq28. Characterisation of the deletion allowed us to position the MTM1 gene to a 600 kb region between DXS304 and DXS497. In order to further restrict the region we screened for deletions in a set of 38 patients. We found two overlapping deletions in boys that in addition to MTM1 showed an unexpected abnormal genital development. As the latter phenotype is not found in the other non-deleted MTM1 patients, our observations are best explained by a contiguous gene syndrome. The deletions define a 430 kb region that contains the MTM1 gene and most likely a gene implicated in male sexual development. A high resolution physical map of this region is presented.
We hypothesized that the hypothalamic gonadotropin-releasing hormone (GnRH) signal that initiates sexual maturation is further amplified at both the pituitary and gonadal levels during puberty. To test this theory, six GnRH-deficient men were monitored during administration of exogenous GnRH at a physiological frequency for greater than or equal to 9 mo. GnRH doses were progressively increased until normal testosterone (T) concentrations and secondary sexual development were achieved. This "optimized" dose of GnRH was then sustained for at least 6 mo to allow maturation of the hypothalamic-pituitary-gonadal axis. The GnRH dose was then progressively decreased to a level that had been unable to stimulate normal T secretion before sexual maturation. Changes in pituitary responsiveness were analyzed in four of the six men by comparing gonadotropin responses to identical doses of GnRH before and after sexual maturation. Mean serum luteinizing hormone and follicle-stimulating hormone levels as well as luteinizing hormone pulse amplitudes were greater after the induction of sexual maturation than before despite identical doses of GnRH. Both pituitary and gonadal responsiveness was then analyzed in the remaining two subjects by choosing periods of evaluation where endogenous gonadotropin levels were matched before and after the period of sexual maturation. Serum T concentrations were greater after sexual maturation than before despite equivalent gonadotropin input to the testes and LH pulse amplitudes. Thus the testicular responsiveness to gonadotropins increased during sexual maturation. After initiation of puberty by GnRH secretion, amplification at both the pituitary and gonadal levels contributes to sexual maturation in the human.
The androgen receptor (AR) is a transcription factor belonging to the family of nuclear receptors which mediates the action of androgens in the development of urogenital structures. AR expression is regulated post-translationally by the ubiquitin/proteasome system. This regulation involves more complex mechanisms than typical degradation. The ubiquitin/proteasome system may regulate AR via mechanisms that do not engage in receptor turnover. Given the critical role of AR in sexual development, this complex regulation is especially important. Deregulation of AR signalling may be a causal factor in prostate cancer development. AR is the main target in prostate cancer therapies. Due to the critical role of the ubiquitin/proteasome system in AR regulation, current research suggests that targeting AR degradation is a promising approach.
The studies conducted in adolescents with physical underdevelopment allowed a conclusion on reduced anabolic processes particularly growth process at the expense of both STH and sex steroids: T and E2. Studies of sex steroid and gonadotrophic hormone concentrations in blood serum revealed dysfunction of the hypothalamo-hypophyseal-gonadal system in this group of patients. Evaluation of androgen receptor level in protein cytosol fraction from the pubic skin of undersized youths with delayed sexual development demonstrated its significant reduction against the control group that may be explained by incomplete ability for androgen receptor synthesis due to relatively low T-level and its biologically active free fraction and low sensitivity of target tissues to androgens as a result of dissociation between functional activity of STH and T.
The sexual relations of parents at the postpartum stage have been researched relatively often, but still there exist serious research deficits (for example, neglect of male partners, of the later postpartum stages beyond the third month, and neglect of sexual feelings, enjoyment and orgasm). The aim of this study was to gain more knowledge about German couples' sexual enjoyment and orgasm with regard to non-genital tenderness, French kissing, breast stimulation, manual-genital stimulation, cunnilingus, fellatio, vaginal intercourse, anal intercourse and masturbation at seven months postpartum. As part of a larger longitudinal study 60 women and men (30 couples) answered a newly developed Sexual Preferences Questionnaire (SPQ), which assesses sexual activity and enjoyment. Descriptive data about sexual enjoyment, sex/gender differences and perceptual differences between self-report and reports of partners' enjoyment are analyzed and SPQ data are validated with interview and other questionnaire data (PFB-tenderness). Both genders find the same activities most pleasant (tenderness, vaginal intercourse, receiving manual-genital stimulation) and most exciting (intercourse, receiving manual-genital and oral-genital stimulation) and reach orgasm most easily through intercourse, masturbation and receiving manual-genital stimulation. But men generally describe a higher sexual enjoyment and overestimate their partners' enjoyment, especially with regard to female orgasm through intercourse. The results are critically discussed with regard to limitations and strengths of the sample and the method.
OBJECTIVES: Patients with Turner syndrome (TS) may present a wide spectrum of gonadal function including spontaneous menstruation and fertility. DESIGN: The aim of our study was to present the patients with Turner syndrome (TS) with spontaneous menstruations considering specific karyotype and X-inactivation processes. MATERIALS AND METHODS: 5 women from group of 55 patients in age from 15 to 38 years with diagnosis of TS and gonadal function were found. Clinical analysis included the evaluation of spontaneous pubertal development and hormones levels. Cytogenetic analysis was performed on peripheral blood samples using GTG banding technique. X inactivation studies were done by dynamic RBG technique. RESULTS: In two patients with mosaic karyotype and predominant 46,XX line two pregnancies were observed. They had regular menses and normal sexual development. In one patient (karyotype: 45,X[2]/46,XX[98]) spontaneous abortions and premature birth were present. Second patient was (46,XX[245]/46,X,r(X)(p22q26)[5]) in pregnancy in this time. Another three patients menstruated irregularly. The menarche appeared later. The karyotypes were: 46,X,del(X)(p11.3) in two patients and 45,X[64]46,X,r(X) (p22q26)[18]/46,XX[4] in one. CONCLUSIONS: We conclude that spontaneous menstruations and possibility of pregnancy depend on specific karyotype in patients with TS.
When administered in overtly toxic doses to postweanling male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces adverse effects on the reproductive system including a decrease in spermatogenesis. Because the male reproductive system may be particularly susceptible to toxic insult during the perinatal period, the effects of in utero and lactational TCDD exposure on its development were examined. Male rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated at various stages of development; effects on spermatogenesis and male reproductive capability are reported herein. Testis, epididymis, and cauda epididymis weights were decreased in a dose-related fashion at 32, 49, 63, and 120 days of age, that is, when males were at the juvenile, pubertal, postpubertal, and mature stages of sexual development, respectively. When measured on Days 49, 63, and 120, daily sperm production by the testis was reduced at the highest maternal TCDD dose to 57-74% of the control rate. Cauda epididymal sperm reserves in 63- and 120-day-old males were decreased to as low as 25 and 44%, respectively, of control values, although the motility and morphology of these sperm appeared to be unaffected. The magnitude of the effects described above tended to lessen with time; nevertheless, the decreases in epididymis and cauda epididymis weights, daily sperm production, and cauda epididymal sperm number were statistically significant at the lowest maternal dose tested (0.064 micrograms TCDD/kg) on Day 120 and at most earlier times. To determine if in utero and lactational TCDD exposure also affects male reproductive capability, rats were mated at approximately 70 and 120 days of age with control females. Little if any effect on fertility was seen, and the survival and growth of offspring was unaffected. These results are not inconsistent with the pronounced reductions in daily sperm production and cauda epididymal sperm reserves caused by perinatal TCDD exposure since rats produce and ejaculate far more sperm than are required for normal fertility. The TCDD-induced reduction in spermatogenesis cannot be accounted for by concurrent effects on plasma follicle-stimulating hormone or androgen concentrations or by undernutrition. To investigate the nature of the spermatogenic lesion, leptotene spermatocyte to Sertoli cell ratios were determined.(ABSTRACT TRUNCATED AT 400 WORDS)
The aim of the present work was to investigate the neuroendocrine control of pituitary somatolactin (SL) release using dispersed pituitary cell culture obtained from male European sea bass (Dicentrarchus labrax) at different stages of sexual development. The effect of mouse recombinant leptin, sea bream gonadotropin releasing-hormone (sbGnRH) and porcine neuropeptide Y (pNPY) and their potential interaction on the SL release were investigated. High doses of leptin (10(-8)-10(-6)M) were differentially effective in inducing SL release depending on the sexual developmental stage. Porcine NPY alone was not effective on basal SL release, but it dose-dependently (0.1 and 1 nM) enhanced SL release induced by leptin (10(-6) and 10(-8)M) in late pre-pubertal but not in post-pubertal stages. No effect of sbGnRH in association or not with leptin was observed on SL release. These findings are the first evidences that leptin and pNPY can play an important role in the neuroendocrine control of pars intermedia function and SL release in fish. In addition, the sensitivity of SL producing cells to leptin and NPY only in prepubertal and pubertal stages, provides the potential role of SL in the nutritional control of the onset of puberty.
1. Broiler breeder pullets were maintained on 10-, 11-, 12-, 13-, 14- or 16-h photoperiods to determine the effect of constant photoperiods on sexual development in broiler breeders. The birds were fed to achieve a 2100 g body weight at approximately 17 or 20 weeks to see if the photosexual response was modified by rate of growth. 2. In both body weight groups, pullets maintained on 10h were the first to reach sexual maturity (50 eggs/100 bird-d), and these and the 11-h pullets matured significantly earlier than any of the other photoperiod groups. Pullets maintained on 13 or 14 h matured latest, at about 3 weeks after the 10-h pullets, though both were only marginally later than the 12- or 16-h birds. These differences in maturation probably reflect the different rates at which photorefractoriness is dissipated in broiler breeders reared on photoperiods that vary in their degree of stimulatory competence. 3. There were no significant interactions among the photoperiods and the ages at 2100 g; faster-growing birds consistently matured about 10 d earlier than conventionally grown pullets.
Excitatory amino acids, particularly glutamate, are thought to be important for the maturation of the brain-pituitary-gonadal axis and the induction of puberty in the rat. We have previously shown that, in the female rat, GnRH neurons preferentially express the KA2 and NMDAR2A receptor subunit mRNAs, but not AMPA or NMDAR1 mRNA. The aim of the present study was to determine whether the onset or rate of KA2 and NMDAR2A receptor expression in GnRH neurons is correlated with the onset of puberty. Dual in situ hybridization using digoxigenin-labeled GnRH cRNA probes and 35S-labeled glutamate receptor subunit probes, followed by autoradiography and image analysis were used to measure the KA2 or NMDAR2A mRNA content in GnRH neurons in 20- to 50-day-old female rats which were sacrificed at 08.00 or 17.00 h. The results show that: (a) the KA2 mRNA content of GnRH neurons and the number of GnRH neurons expressing KA2 mRNA increase progressively in the morning hours between postnatal days 20 and 40; (b) the diurnal pattern of KA2 mRNA levels in GnRH neurons changes between days 40 and 50 from high KA2 levels in the morning hours before day 40 to high KA2 mRNA levels in the afternoon in 45- and 50-day-old animals; (c) while the high levels of KA2 mRNA in GnRH neurons in the morning hours of 20- to 40-day-old animals are paralleled by an overall increase in KA2 expression in the preoptic area, the rise in KA2 mRNA in GnRH neurons in the afternoon of 45- and 50-day-old animals appears to be specific for the GnRH neurons, and (d) no significant differences were detected for the NMDAR2A mRNA content in GnRH neurons among the different age groups and the morning and afternoon values. Since the gradual increase in the KA2 mRNA content in GnRH neurons of animals reaching puberty as well as the reversal of diurnal rhythmicity in KA2 receptor mRNA content of GnRH neurons coincide with the times of vaginal opening and first ovulation, it is suggested that glutamate, acting through KA2 receptors directly on GnRH neurons is, at least in part, an important factor in the excitatory regulation of the postnatal sexual development of the female rat. In contrast, expression of the NMDA-preferring receptor, NMDAR2A, in GnRH neurons appeared to be unchanged during this development.