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PubMed1975

Pseudohermaphroditis, with testes and a 46, XX karyotype.

A 14 4/12-year-old white girl, evaluated for progressive virilization and clitormegaly, was found to have the unusual combination of a 46, XX karyotype, well-developed Mullerian structures, and dysgenetic testes with Leydig cell hyperplasia. Although there have been previous case reports of 46, XX males, in all of these patients development of the Mullerian ducts had been suppressed. When contemporary classifications of human disorders of sexual differentation were reviewed, no report of a similar patient was found. We speculate that the genotype and phenotype in our patient correspond to the genetic intersexuality of the hornless goat, thereby raising the possibility that the human autosome may play a role in the control of sexual development.

Adolescent↗
PubMed1998

Follitropin (FSH) deficiency in an infertile male due to FSHbeta gene mutation. A syndrome of normal puberty and virilization but underdeveloped testicles with azoospermia, low FSH but high lutropin and normal serum testosterone concentrations.

We studied a man who sought medical attention at age 28 years because of infertility in both his first and second marriages. His sexual development appeared to have been normal, with normal puberty and virilization, and normal libido and sexual potency. At examination, his testicles were small and soft; otherwise he had a normal physical appearance. Evaluations revealed azoospermia, undetectable in serum before and after 100 microg of intravenously administered gonadotrophin releasing hormone, but moderately elevated lutropin concentration with a brisk rise after gonadotrophin releasing hormone. The alpha subunit concentration was normal before and after gonadotrophin releasing hormone; that of inhibin B was very low. Analysis of the follitropin beta gene, exon 3, revealed a Cys82 --> Arg mutation (TGT --> CGT). Judging from studies of the biosynthesis of the chorionic gonadotrophin beta subunit one may conclude that inability to form the first intramolecular disulphide bond in the follitropin beta subunit results in an abnormal tertiary structure during follitropin beta biosynthesis with extensive intracellular degradation of the products, inability to associate with the alpha subunit and defective glycosylation, as well as inability to form a biologically active hormone. This first male case of follitropin deficiency thus defines a new syndrome of male infertility.

Adult↗
PubMed2000

ACL injuries in the skeletally immature patient.

Anterior cruciate ligament injuries are becoming increasingly prevalent in a younger, more athletic population. These injuries require aggressive management given the poor natural history with regard to progressive meniscal damage and advanced degenerative changes. In general, strict nonoperative management has been associated with failure in the individual committed to return to an active lifestyle. As a result a general algorithm can be expressed as follows: 1. Activity limitations and bracing are initially used for the asymptomatic skeletally immature patient with a complete ACL tear. 2. If the patient remains asymptomatic, formal reconstruction can be delayed until skeletal maturity. 3. For the symptomatic patient a precise delineation of their physical development or skeletal age is important. 4. In patients who have reached Tanner IV secondary sexual development or a skeletal age of 13-14 (F/M), a traditional transphyseal reconstruction with hamstring autografts is appropriate. 5. In the skeletally immature patient who has significant skeletal development ahead of them, the judicious use of physeal sparing procedures is an option for the surgeon comfortable with these techniques. In this case the goal is temporization until formal transphyseal reconstruction can be performed after the peak of skeletal growth.

Adolescent↗
PubMed2005

Genes involved in the neuroendocrine control of normal puberty and abnormal puberty of central origin.

There is now compelling evidence that both normal puberty and disturbed pubertal development of central origin are, to a significant extent, determined by genetic factors. Although delayed sexual development can result from a deficient pituitary responsiveness to GnRH caused by mutations in the GnRH receptor gene, until recently the only genetically determined hypothalamic defects known to affect puberty were those caused by mutations in genes required for the migration of gonadotropin releasing hormone (GnRH) neurons, such as KAL1, FGFR1, and NELF. Recently, mutations in a gene termed GPR54 were identified as causing isolated hypogonadotrophic hypogonadism (IHH), due to a functional, instead of a structural hypothalamic defect. Studies in nonhuman primates and rodent models suggest that the functional integrity of the hypothalamic mechanism controlling puberty requires a gene network that includes GPR54. Altogether, these findings indicate that the genetic underpinnings of disturbed pubertal development of central origin are polygenic, rather than specified by a single gene.

Animals↗
PubMed1991

[The psychosocial development of boys treated with pulsatile LHRH administration for hypogonadotropic hypogonadism].

Eight male adolescents with hypogonadotropic hypogonadism, who were being treated with pulsatile GnRH administration, were examined psychologically. We focused on the development of independence and on the manner in which they experienced their illness and treatment. The patient group was compared with a group of male adolescents of normal height and a group of male adolescents of short stature. We found that there were problems in the patient group in the development of independence, specifically relating to their own body image and social functioning. The retarded sexual development of these patients is probably of greater importance than the height growth-related problems, if any. The problems we found appeared to be caused primarily by the presence of the physical disorder and not by the stress of treatment.

Adolescent↗
PubMed1989

[Dysthyroidism and fertility].

The role of the thyroid gland in sterility is not well known; hyperthyroidism may have an effect upon estrogen secretion by decreasing the level of the free forms of estradiol, resulting in a lowering or disappearance of the LH ovulatory peak. Clinically, severe hypothyroidism would cause a retarded sexual development but simple hypothyroidism and hyperthyroidism do not seem to have a major effect upon sexual maturity. During the period of genital activity, hyperthyroidism may result in amenorrhea and dysovulation phenomena reminding of ovarian dystrophy; hypothyroidism results in the same phenomena, with decreased libido, but with a better screening process and a better adjusted substitute treatment, these disorders are rare. Finally, systematic evaluation of the thyroid function in unexplained sterilities, appears unnecessary most of the time.

Female↗
PubMed2003

Gonadotropin-releasing hormone receptor gene expression during pubertal development of female rats.

Appropriate expression of the GnRH receptor (GnRH-R) in gonadotrophs is critical for GnRH signaling and hence for gonadotropin secretion and sexual development. In the present work, we have studied the ontogeny of the steady-state GnRH-R mRNA levels in pituitaries of female rats from Day 5 to Day 55, when sexual maturity is attained. Developmental changes of gonadotropin subunit (alpha, FSHbeta, and LHbeta) mRNA levels were also assessed. In addition, the role of the endogenous GnRH on the maturational changes of GnRH-R and gonadotropin subunit gene expression was investigated. Messenger RNA levels were determined by Northern blot analysis of total RNA from anterior pituitaries. Amounts of the most abundant (5.0 kilobase [kb]) GnRH-R mRNA increased slowly from Day 5 through the infantile period, to peak at Day 20 ( approximately 4-fold increase vs. Day 5). Thereafter the levels of the GnRH-R mRNA decline abruptly by Day 25 (75% decrease vs. Day 20) and then fell slightly until Day 35. Parallel changes were observed on the 4.5-kb transcript of the GnRH-R gene. Alpha subunit mRNA was easily detected at Day 5 and its levels increased quickly through the beginning of the infantile period to peak at Day 10 (3.2-fold increase vs. Day 5); then it decreased by 85% at Day 35. FSHbeta and LHbeta mRNA levels rose slowly until Days 15-20, a short time before GnRH-R. Thereafter, the levels of both mRNAs fell until Day 35 (90% decrease vs. Day 15 for FSHbeta and 50% decrease vs. Day 20 for LHbeta). To ascertain whether developmental activation of the GnRH-R and gonadotropin subunit gene expression is GnRH dependent, we have studied the effect of blocking the endogenous GnRH action by treating developing female rats with the specific GnRH antagonist cetrorelix (1.5 mg/kg body weight/wk, s.c.) through the infantile (Days 5-20) and the juvenile period (Days 20-35). Cetrorelix completely blocked the rise of levels of the two most abundant species, 5.0 kb and 4.5 kb, of GnRH-R mRNA during the infantile phase and dropped them to almost undetectable levels during the juvenile prepubertal period. Cetrorelix also abolished the developmental rise of gonadotropin beta subunit mRNAs during the two periods of the study. In contrast, alpha subunit gene expression tended to decrease, but not significantly, with cetrorelix treatment during the two periods. These data demonstrate that sexual maturation of female rats is advanced by an early and strong induction of GnRH-R and gonadotropin subunit gene expression during the infantile period, followed by weaker persistent activation during puberty. Developmental GnRH-R and gonadotropin beta subunit gene expression is almost entirely GnRH dependent, not only in the juvenile prepubertal stage but also during the infantile period.

Animals↗
PubMed2002

Gonadotropin-releasing hormone receptor gene expression during pubertal development of male rats.

Appropriate expression of the GnRH receptor (GnRH-R) in gonadotropes is critical for GnRH signaling and hence for gonadotropin secretion and sexual development. In the present work, we have studied the ontogeny of the steady-state GnRH-R mRNA levels in pituitaries of male rats from Day 5 to Day 55, when sexual maturity is attained. Developmental changes of gonadotropin subunit (alpha, FSHbeta, and LHbeta) mRNA levels were also assessed. In addition, the role of the endogenous GnRH on the maturational changes of GnRH-R and gonadotropin subunit gene expression was investigated. Messenger RNA levels were determined by Northern blot analysis of total RNA from anterior pituitaries. Amounts of the most abundant (5.0 kb) GnRH-R mRNA increased slowly from Day 5 through the infantile and the juvenile periods, to peak at Day 35 (12-fold increase vs. Day 5). Thereafter, the levels of the GnRH-R mRNA decline slightly until Day 55 (33% decrease vs. Day 35). Parallel changes were observed on the 4.5-kb transcript of the GnRH-R gene. Alpha subunit mRNA was easily detected at Day 5, and its levels increased progressively through the infantile period (2.5-fold increase) and peaked at Day 25 (3.3-fold increase vs. Day 5) with a smooth nonstatistically significant increment until Day 35; then it decreased by 41.5% at Day 55. FSHbeta and LHbeta mRNA levels rose slowly until Day 25. A sharp rise occurred thereafter to reach maximum levels at Day 35 (5.8-fold for FSHbeta and 3.8-fold for LHbeta vs. Day 25). Thereafter, the levels of both mRNAs fell until Day 55 (44.1% decrease for FSHbeta and 37.1% decrease for LHbeta vs. Day 35). To ascertain whether developmental activation of the GnRH-R and gonadotropin subunit gene expression is GnRH dependent, we have studied the effect of blocking the endogenous GnRH action by treating developing male rats with the specific GnRH antagonist cetrorelix (1.5 mg/kg body weight/week, s.c.) through the infantile (Days 5-20) and the juvenile periods (Days 20-35). Cetrorelix completely blocked the rise of levels of the two most abundant species, 5.0 kb and 4.5 kb, of the GnRH-R mRNA, during both the infantile and the juvenile periods. Cetrorelix also abolished the developmental rise of the gonadotropin beta subunit mRNAs during the two periods of the study. In contrast, the alpha subunit gene expression was not altered by cetrorelix treatment during any of the two periods. These data demonstrate that sexual maturation of male rats is accompanied by a progressive and concerted induction of GnRH-R and gonadotropin subunit gene expression. Developmental activation of GnRH-R and gonadotropin beta subunit genes is GnRH dependent. The apparent GnRH-independent regulation of the alpha-glycoprotein subunit mRNA levels may be due to the contribution of thyrotropes and perhaps to the presence of exclusive regulatory signals for this gene.

Animals↗
PubMed2006

The impact of delayed development on the quality of life of adults with end-stage renal disease since childhood.

Little is known about the impact of the course of life of children with end-stage renal disease (ESRD) on their quality of life in adulthood. We therefore assessed the course of life of adult patients with onset of ESRD at an age of <15 years between 1972 and 1992 and compared it with that of the general population. Furthermore, we explored how course of life is associated with quality of life (QoL) in young adulthood. A total of 75 young adult patients who had had ESRD since childhood, aged between 20 years and 30 years, completed the RAND-36 Health Survey and a questionnaire, which retrospectively assesses the achievement of development milestones. Patients achieved fewer milestones than peers with respect to autonomy, social, and psycho-sexual development, and displayed less risk behaviour. Patients who achieved fewer social milestones while growing up experienced more emotional problems and less vitality, and they had a lesser overall mental quality of life. Paediatric nephrologists should pay more attention to the development of social and independent functioning of children with ESRD in order to prepare them for active participation in society in adult life.

Adult↗
PubMed1999

TRA-1 regulates the cellular distribution of the tra-2 mRNA in C. elegans.

The GLI protein family is involved in several key developmental processes in both vertebrates and invertebrates. The Drosophila GLI protein, Cubitus interuptus (Ci), regulates segment polarity and wing and leg development. In vertebrates, the GLI proteins control neural, lung, bone and gut development. In the nematode Caenorhabditis elegans, the GLI family member TRA-1 is necessary for normal sexual development. GLI, Ci and TRA-1 each contain five zinc-finger domains and bind the identical DNA sequence. Previous analyses are consistent with these proteins being transcription factors. Here we show that TRA-1 can act posttranscriptionally to govern gene activity. Our results indicate that the binding of TRA-1 to the 3' untranslated region of tra-2 regulates the export of tra-2 messenger RNA from the nucleus. The fact that TRA-1 is part of a conserved family of proteins raises the possibility that GLI family members are both transcriptional and post-transcriptional regulators of gene expression.

3' Untranslated Regions↗
PubMedDate not supplied

[Development of sex characteristics in adolescents in the forest regions of Ukraine].

A total of 3019 adolescents were examined residing in those territories of the Zhitomir and Vinnitsa Regions affected by radionuclide contamination, who ranged from 15 to 18 years old. Revealed in the above juvenile population was a stimulating effect of small doses of ionizing radiation on some parameters characterizing somatosexual development in adolescents 15 years old, that tends to smooth down with stabilization of physical and sexual development.

Adolescent↗
PubMed2003

[Pregnancy and delivery after traumatic panhypopituitarism].

OBJECTIVE: We describe a case of 23 years old woman who, with a history of car accident at the age of 11 and severe head injury, attended our Center of Reproductive Medicine complaining of primary infertility. The accident preceded menarche and the development of inner genitalia (uterus 46 mm, cervix:corpus ratio 1:1) as well as secondary sexual development was not fully accomplished. Ovarian failure was accompanied by amenorrhea, if not substituted. Under replacement therapy regular menstruation was established. Basal hormonal levels was extremely low (FSH and LH 0.2-0.3 IU/l, PRL 0.5 ng/ml, estrogens 0.08 nmol/l, PRGE was not detected). With oral administration of micronized estradiol (Check et al., 2001) endometrial thickness of 9 mm was achieved. All of five retrieved oocytes were fertilized with partner sperm (normospermy) and three embryos were transferred. Already the first attempt was successful. Patient suffered with transitional anorexia and vomiting which could be handled conservatively. Hormonals level were normal. Patient substituted with Hydrocortison and Euthyrox. On January 2, 2003 the pregnancy was finished by caesarian section, one week before the delivery term (girl, 2970, Apgar score 10-10-10). DESIGN: Case report. SETTING: Center of Reproductive Medicine, Zlin. CONCLUSION: This care report demonstrates that recent progress in assisted reproduction field enables to manage successfully even exceptional pathological conditions.

Adult↗
PubMed1984

[Blood testosterone levels in nonpsychotic psychopath-like behavior disorders among adolescents with accelerated or delayed physical development].

The authors examined 128 male adolescents admitted to a psychiatric hospital for the psychopathlike syndrome free of psychotic manifestations which was associated with the abnormal rate of sexual development. A correlation was established between the maturation rate, plasma testosterone levels and clinical features of behavioural abnormalities. Retarded puberty was related to decreased testosterone concentrations throughout the pubertal period. In cases of accelerated development the testosterone content was increased at the age of 14-15 years, i.e. in the period of the most intensive maturation; later on, in the process of reaching puberty, the hormone level approaches the age specific rate. The clinical picture of behavioural disorders in the presence of retarded or accelerated development depends on whether the symptoms caused by abnormal rates of maturation were combined with the symptoms of cerebral insufficiency. Adolescents with accelerated development unattended by cerebral insufficiency manifestations were characterized by marked aggression and an increase in desires. Depending on the degree of activity, asthenic nature, leadership capacities and the level of intellect, they are divided into two clinical variants: epileptoid and conformational-epileptoid types of accentuations. Cerebral insufficiency was reflected in the form of lowered intellect, explosiveness and impaired desires in the clinical picture of both accelerated and retarded pubertal development.

Adolescent↗
PubMed2006

Factors that shape young people's sexual behaviour: a systematic review.

BACKGROUND: Since nearly half of new HIV infections worldwide occur among young people aged 15-24 years, changing sexual behaviour in this group will be crucial in tackling the pandemic. Qualitative research is starting to reveal how social and cultural forces shape young people's sexual behaviour and can help explain why information campaigns and condom distribution programmes alone are often not enough to change it. We undertook a systematic review to identify key themes emerging from such research, to help inform policymakers developing sexual health programmes, and guide future research. METHODS: We reviewed 268 qualitative studies of young people's sexual behaviour published between 1990 and 2004. We developed a method of comparative thematic analysis in which we coded each document according to themes they contained. We then identified relations between codes, grouping them accordingly into broader overall themes. Documents were classified as either primary or secondary depending on their quality and whether they contained empirical data. From the 5452 reports identified, we selected 246 journal articles and 22 books for analysis. FINDINGS: Seven key themes emerged: young people assess potential sexual partners as "clean" or "unclean"; sexual partners have an important influence on behaviour in general; condoms are stigmatising and associated with lack of trust; gender stereotypes are crucial in determining social expectations and, in turn, behaviour; there are penalties and rewards for sex from society; reputations and social displays of sexual activity or inactivity are important; and social expectations hamper communication about sex. The themes do not seem to be exclusive to any particular country or cultural background, and all themes were present, in varying degrees, in all countries assessed. INTERPRETATION: This study summarises key qualitative findings that help in understanding young people's sexual behaviour and why they might have unsafe sex; policymakers must take these into account when designing HIV programmes. Considerable overlap exists between current studies, which indicates the need to broaden the scope of future work.

Adolescent↗
PubMed1984

Hormonal correlates of photoperiod-induced puberty in a reflex ovulator, the female ferret (Mustela furo).

In an attempt to develop an animal model wherein the pubertal process could be initiated or accelerated by a readily controlled, noninvasive, external signal, this study examined sexual development of the female ferret, a photoperiodic, reflex ovulator. These animals exhibit signs of precocious sexual maturation within 6 wk of exposure to a stimulatory, long-day photoperiod at 15 wk of age. In the first study, females matured under a long-day stimulus were allowed to mate with a fertile male ferret. All six females ovulated after mating, and three of six became pregnant and successfully delivered and reared litters, demonstrating that vulvar edema induced by long days reflected the onset of true precocious sexual maturation. The second study attempted to determine the endocrine basis of this photoperiod-induced puberty. Immature ferrets were either left intact or were ovariectomized at 13 wk of age. These females either remained untreated or immediately received an estradiol implant. Controls in each group remained in short days, and others were transferred to stimulatory long days at 16 wk of age. Results indicated that immature ferrets exhibited a rise in plasma luteinizing hormone (LH) upon ovariectomy, and that the extradiol implant was an effective negative feedback signal for the duration of the study in animals in short days. In contrast, females in long days exhibited an "escape" from LH inhibition by the steroid implant at the same age at which the intact females in long days were beginning to mature. These data suggest the young ferret exhibits a high sensitivity to estradiol negative feedback which is decreased in response to a stimulatory photoperiod, and which decrease is coincident with sexual maturation in intact animals under the same conditions.

Animals↗
PubMed1989

Photoperiodic control of the development of the LHRH neurosecretory system of European starlings (Sturnus vulgaris) during puberty and the onset of photorefractoriness.

The development of the reproductive system was studied in juvenile starlings during the acquisition of photosensitivity, the attainment of sexual maturation after photostimulation and the subsequent onset of photorefractoriness, using immunohistochemistry for LHRH and radioimmunoassay measurements of hypothalamic, pituitary and plasma hormone concentrations. The first stage of sexual development induced by exposure of photorefractory immature starlings to short days (8 h light:16 h darkness; 8L:16D) was characterized by a decrease in pituitary prolactin content within 1 week and an increase in hypothalamic LHRH content, in the size of the LHRH perikarya and in the intensity of immunostaining in the median eminence in 4-6 weeks. Sexual maturation occurring after exposure to long days (18L:6D) was associated with further increases in LHRH content and cell size, and increases in LH and prolactin concentrations. During testicular regression, LHRH perikarya were reduced in size and staining intensity but LHRH immunostaining in the median eminence and content in the hypothalamus remained high until gonadal regression was almost complete. Prolactin levels were maximal during testicular regression. These results suggest that gonadal regression is initiated by a reduction in LHRH synthesis and possibly, in addition, an external inhibitory influence on LHRH release. Hypothalamic LHRH content eventually declined and LHRH immunostaining in the median eminence was much reduced in fully photorefractory starlings maintained under long days.

Animals↗
PubMed1989

Sexuality in children and adolescents with cancer: pediatric oncology nurses' attitudes and behaviors.

It is essential that health professionals openly discuss how cancer may affect the developing sexuality of childhood cancer patients. This study was conducted to explore nurses' attitudes and behaviors regarding sexuality in cancer patients. Results are reported for a subset of a larger study (N = 937) from subjects who indicated that their practice included children and/or adolescents (N = 156). The Williams-Wilson Sexuality Survey was used to measure attitudes towards sexuality in cancer patients, behavior in nursing care related to the sexuality of a cancer patient, and attitudes towards sexuality in the child and/or adolescent with cancer. The majority of subjects agreed that sexuality should be a routine component of nursing care, yet less than half had actually discussed an alternation in sexuality with an adolescent patient. More than one third said they were not comfortable in initiating such discussions. However, they were comfortable in discussing sexuality concerns when these discussions were initiated by the patient and/or family.

Adolescent↗