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PubMed1983

Intersex disorders in adolescents and adults.

Inasmuch as disorders of sexual development and differentiation are not all diagnosed during the neonatal period, physicians and surgeons do encounter such problems in adolescent and adult patients. Because phenotype and gender identity are usually already firmly established, complaints are likely to be functional. Current cytogenetic and hormonal techniques may clarify the cause of the abnormalities but will rarely lead to sex reversal. The therapeutic goal is, when feasible, to maintain and enhance existing sexual identity.

Adolescent↗
PubMed1995

Investigation of delayed puberty.

Delayed puberty is defined arbitrarily on the basis of statistical consideration, when no signs of puberty have occurred at 2.0 SD (13.4 years in girls and 13.8 in boys) above the mean chronological age for the onset of puberty. The vast majority of these patients have no endocrine abnormality and their pubertal development and growth spurt are simply consequences of primary delay (constitutional delay of growth and puberty (CDGP)) or secondary delay due to a chronic disease of childhood, such as asthma. However, a small proportion may have pathological causes of delayed puberty which must be careful identified as specific management may be required. Associated with delayed puberty, the growth spurt is always delayed which is why the condition is described as delayed growth and puberty. Short stature and lack of sexual development may lead to emotional and social difficulties and in some patients their consequences can persist when 'normal' height and full sexual maturation are attained. Recent data also suggest that a delay in the 'tempo' of pubertal maturation may interfere with the normal bone accretion occurring during puberty, later causing osteoporosis. Such findings suggest that a new approach in delayed puberty may be necessary not only for psychological reasons but also for optimizing bone mass accretion.

Adolescent↗
PubMed1995

Multiple response elements in the Sex-lethal early promoter ensure its female-specific expression pattern.

The choice of sexual identity in somatic tissues of the fruit fly Drosophila melanogaster is determined early in embryogenesis by the X-chromosome-to-autosome (X/A) ratio. The system that signals the X/A ratio selects the sexual development pathway by determining the activity state of the binary switch Sex-lethal (Sxl). In 2X/2A animals, the X/A signalling system turns the Sxl gene on, ultimately activating an RNA-splicing autoregulatory feedback loop which serves to maintain the female state during the remainder of development. In 1X/2A animals, this autoregulatory feedback loop is not activated and the male state is subsequently maintained by the default splicing machinery. In the studies reported here, we have examined how the X/A signalling system controls the initial choice of sexual identity through its action on a special early embryonic Sxl promoter, Sxl-Pe. We show that in the early embryo, the activity of Sxl-Pe is controlled in a highly dose-sensitive fashion by the genes on the X chromosome that function as numerator elements and by genes located on the autosomes that function as denominator elements. Functional dissection of Sxl-Pe indicates that activating the promoter in females requires the cumulative action of multiple numerator genes which appear to exert their effects through reiterated cis-acting target sites in the promoter. Conversely, maintaining the promoter silent in males requires the repressive activities of denominator genes, and at least one of the denominator genes also appears to function through target sequences within the promoter.

Animals↗
PubMed1988

A histological study of the gonads of T16H/XSxr hermaphrodite mice.

A proportion of mice with the genotype T16H/XSxr develop as hermaphrodites (Ward et al. 1987). In this study, histological sections were prepared of the gonads and reproductive tract from a number of such animals. Examination of the sections showed a wide range of development. The most common types of gonad found were sterile testes resembling those found in XXSxr males and apparently normal ovaries. However, between these two extremes were some gonads which were classified as ovotestes. These ovotestes covered such a range of sexual development that they were for convenience divided into two groups. Type I ovotestes were similar in appearance to the Sxr-type testes with the exception that oocytes surrounded by granulosa-like cells were present in some seminiferous tubules. Also, many tubules had shed their Sertoli cell lining. The structure of Type II ovotestes was even more bizarre; regions of both testicular and ovarian somatic tissue and widespread areas of haemorrhage were seen. In general, the histological structure of the reproductive ducts approached the normal pattern. The epididymal ducts were small and haemorrhage was present in some epididymides associated with the Type II ovotestes.

Animals↗
PubMedDate not supplied

Gender differences in leptin levels and physiology: a role for leptin in human reproduction.

Leptin, an adipocyte-derived hormone known to play an important role in body-weight regulation, has been shown to be expressed differentially in men and women. These observations are potentially important for the understanding of differences between men and women in regulation of food intake, weight gain, and body fat distribution. Leptin is also involved in female fertility, especially in pubertal development. It may well be the triggering signal for the onset of puberty in girls. Although the exact mechanisms and interactions with sex steroids are not yet fully established, it is clear that leptin plays a role as an endocrine mediator in sexual development and reproduction.

Animals↗
PubMed2004

[The abnormalities of pubertal development: a review of treatment for them].

Precocious puberty has been defined as the development of secondary sex characteristics before 8 years of age in girls. In the past, therapy with progestational agents, such as medroxyprogesterone acetate or cyproterone acetate had been used. The gonadotropine releasing hormone agonist has been used widely. The ethiologies of delayed sexual development are numerous. A series of 191 patients with delayed pubertal development is reported in this study. Gonadal dysgenesis is 39/119(32.8%), physiologic delay is 27/119(22.7%), Rokitansky syndrome is 17/119(14.3%), hyperprolactinemia is 11/119(9.2%). The girls with physiological delay, hyperprolactinemia or poly cystic ovary syndrome, have subsequent normal reproductive potential. In the treatment of abnormal pubertal development, the individual treatment is important.

Child↗
PubMedDate not supplied

Growth and reproductive adaptation in male rats with chronic protein deficiency.

In previous studies, male rats fed a low-protein diet beginning at weaning were found to have impaired sexual development through age 11 weeks when compared to food-restricted, weight-matched controls fed a diet with normal protein content. To determine whether male rats show long-term adaptation of the reproductive axis to low-protein feeding, we assessed sexual maturation and growth in rats fed a low protein (9%) diet from weaning until sacrifice at various points in time between ages 79 and 185 days. After age 80 days, there was no difference in reproductive organ weights (prostate, seminal vesicles, testis) or serum hormone levels (luteinizing hormone, follicle stimulating hormone, testosterone) between protein-deficient animals and food-restricted weight-matched controls given a normal diet. In addition, there was no difference between protein-deficient animals and controls in indices of linear growth (naso-anal and tail length) or fatness (Lee index). We conclude that both growth and reproductive function of male rats show adaptation to long term feeding of a low-protein diet.

Adaptation, Biological↗
PubMed2006

Sry and the hesitant beginnings of male development.

In mammals, Sry (sex-determining region Y gene) is the master regulator of male sex determination. The discovery of Sry in 1990 was expected to provide the key to unravelling the network of gene regulation underlying testis development. Intriguingly, no target gene of SRY protein has yet been discovered, and the mechanisms by which it mediates its developmental functions are still elusive. What is clear is that instead of the robust gene one might expect as the pillar of male sexual development, Sry function hangs by a thin thread, a situation that has profound biological, medical and evolutionary implications.

Amino Acid Sequence↗
PubMed1980

The effects of exercise on pubertal progression and reproductive function in girls.

To determine whether a significant energy drain during adolescence had a significant effect on puberty and normal reproductive function, 15 ballet dancers, aged 13--15 yr, who maintained a high level of physical activity from early adolescence were followed for 4.0 yr. Menarche was remarkably delayed in this group, occurring at a mean of 15.4 yr, significantly different (P < 0.01) from normal controls (12.5 yr) and normal music students (12.6 yr). In 2 dancers aged 18 yr, primary amenorrhea has persisted. While premenarchial, all of the dancers had varying breast development (Tanner stages 2--4) and low to low normal gonadotropin levels, normal PRL and T4 levels, and normal skull x-rays. The dancers' mean body weight and calculated body fat were significantly less than in controls (P < 0.05). The progression of sexual development and the onset of menarche correlated in 10 or 15 subjects with a decrease in exercise and/or injury causing forced rest of at least 2-month duration. During this interval, weight gain was minimal or absent, with no significant change in body composition. A significant dichotomy in the order of pubertal development was also noted; while breast development and menarche were delayed, pubic hair development was not affected. Reversion to the amenorrheic state occurred in 11 of 13 patients with a return to exercise without a change in weight. In conclusion, energy drain may have an important modulatory effect on the hypothalamic pituitary set point at puberty and, in combination with low body weight, may prolong the prepubertal state and induce amenorrhea.

Adolescent↗
PubMed1983

[Precocious puberty in boys. Study of a series of 34 cases].

Thirty-four boys with true precocious puberty were observed: In 28, precocious puberty was related to intracranial causes (17 tumors, 11 other lesions), in 3, it was due to extrapituitary gonadotropin-secreting tumors and in 3 it appeared idiopathic. The clinical development of sex characteristics was slower than the advance of bone age and the increase in hormone levels (plasma testosterone and pituitary gonadotropin reserve as measured by the LH-RH test). Cyproterone treatment seemed more effective than medroxyprogesterone, with respect to both sexual development and evolution of the bone age/height age ratio or the predictable adult height.

Body Height↗
PubMedDate not supplied

Postweaning exposure to gossypol results in epididymis-specific effects throughout puberty and adulthood in rats.

Gossypol, a yellow pigment found in cottonseeds, well known for its antifertility properties in animals, has been used as a contraceptive by men. The aims of this work were to evaluate the effects of gossypol throughout sexual development of male rats and to provide additional data to clarify the target site or sites of this compound in the male reproductive system. Gossypol (15 mg/kg per day) was given to animals from weaning through prepuberty (41 days), early puberty (51 days), puberty (61 days), and sexual maturity (91 days). Ventral prostate weight and fructose levels were similar in control and treated rats, suggesting that androgen levels were normal. No histological effects on the testis were detected, but there was a significant decrease in the sperm concentration in the cauda epididymidis of gossypol-treated animals killed at 61 and 91 days, as well as a significant increase in abnormal sperm in the vas deferens of treated animals. Moreover, the histology of the cauda epididymidis of the rats treated throughout puberty (ie, until days 51 and 61) showed a great number of round bodies in the lumen of the epididymis. These structures stained for the epididymis-specific protein E. Collectively, the data demonstrate that the epididymis is a target of gossypol when postweaning exposure extends throughout pubertal development, and that whereas more subtle histological effects commence around puberty, indicators reproductive competence are compromised in adulthood.

Aging↗
PubMed2005

The relationship between secretory patterns of gonadotrophic hormones and the attainment of puberty in bull and heifer calves born early or late during the spring calving season.

It was suggested that an early increase in gonadotrophin secretion in calves aged between 6 and 24 weeks might be critical for initiating developmental changes culminating in puberty. An early rise in luteinizing hormone (LH) release appears to be caused by an increase in LH pulse frequency in bull calves and by an increase in LH pulse amplitude in heifer calves. Previously we have found differences in the characteristics of the LH rise between prepubertal beef calves born in spring or fall; however, age at puberty was not affected by season of birth. Here we report the LH/FSH secretory patterns in prepubertal bull and heifer calves (Hereford x Charolais), born in March or April, respectively (i.e., early or late during the spring calving season; six animals of each sex born at each time). The bull calves of both groups reached puberty (defined as an attainment of scrotal circumference of >or=28 cm) at 43.2+/-1.3 weeks of age (P>0.05). Age at puberty for March- and April-born heifer calves (defined as the age at which serum progesterone concentrations first exceeded 0.4 ng/ml) averaged 56.0+/-1.4 weeks (P>0.05). Based on blood samples taken weekly from birth to 26 weeks of age, and then every other week until puberty, bull calves born in March exceeded April-born bull calves in mean serum LH concentrations at 6, 10 and 12 weeks of age (P<0.05). Mean FSH concentrations were greater (P<0.05) in March-born compared to April-born bull calves from 34 to 32 weeks before puberty. Mean serum LH (at 40, 42 and 56 weeks) and FSH concentrations (at 2, 10, 20, 22-26, 30 and 56 weeks of age) were greater (P<0.05) in heifer calves born in April than March. On the basis of frequent blood sampling (every 12 min for 10 h), heifer calves born in April exceeded March-born animals in mean LH and FSH concentrations, at 5 and 25 weeks, and LH pulse frequency, at 5, 10 and 25 weeks of age (P<0.05). None of the parameters of LH secretion (i.e., mean concentrations of LH, LH pulse frequency and amplitude based on frequent blood collection) differed between March- and April-born bull calves in this study (P>0.05). In summary, March-born bull calves had greater mean serum LH and FSH concentrations prior to 24 weeks of age than April-born calves. April-born heifer calves had greater mean serum concentrations of LH and FSH but this difference was not confined to the early postnatal period. Although there were significant differences in absolute amounts of LH secreted, there were no differences in the frequency of LH secretory pulses amongst March- and April-born bull calves and no differences in LH pulse amplitude in heifer calves born in March or April. As these particular parameters of LH secretion, as well as age at puberty, are not affected by the time or season of birth, they may be primary hormonal cues governing sexual development in bulls and heifers, respectively.

Aging↗
PubMed1985

Inhibition of testicular androgen biosynthesis by chronic administration of a potent LHRH agonist in adult men.

The antireproductive properties of LHRH and its agonists have now been clearly established. Using various dosing regimens and routes of administration in animal experiments and in clinical trials, these peptides invariably produce paradoxical inhibitory effects on reproductive function. This ability led to the concept that gonadal steroid-dependent (responsive) tumors might also be affected in a manner analogous to that produced by gonadectomy or by antiandrogenic or antiestrogenic drugs. Numerous data have now appeared in the medical literature on the potential efficacy of the LHRH agonists as a tumor therapy. Using different agonists (D-Ser6, D-Leu6 and D-Trp6-LHRH) and various dosages, the investigators were successful in inducing a "medical castration" with androgen levels comparable to castrate control subjects. Objective tumor regression and significant clinical improvement paralleled the hormonal suppression shown in our studies and by other groups. Another interesting potential clinical application of the ability of LHRH agonist to inhibit testicular function is its development as a male contraceptive. This approach is being tested by a few groups. In order to preserve potency, exogenous androgens must be administered with the agonist. Long-term pituitary suppression in boys with idiopathic precocious puberty has now been achieved and premature sexual development suppressed. In man the main mechanism responsible for testicular inhibition seems to be the achievement of a temporary and reversible state of hypogonadotropic hypogonadism. Recent data show that LHRH agonist alters the ratio of bioactive and immunoreactive LH and suggest a direct effect on LH biosynthesis as a mechanism of action of LHRH agonist analogs. Other findings support the lack of direct effect of LHRH agonist on Leydig cells in humans. In view of the main potential clinical applications--as therapy for chronic hormone-dependent disease or as a male contraception--major new developments are being undertaken in the way of administration of these substances by slow delivery systems.

Administration, Intranasal↗
PubMed1996

Analysis of the role of Amh and Fra1 in the Sry regulatory pathway.

Sry is the Y-chromosomal gene responsible for initiating the pathway of male development in mammals, presumably by regulating downstream target genes. As a basis for examining the role played by Sry and other candidate sex-determining genes, we have used reverse-transcriptase PCR to produce a precise temporal profile of expression of Sry in the developing gonad. Sry expression first occurs at 10.5 days postcoitum (dpc) and is upregulated to reach a maximum level from 11.25 to 12 dpc. Expression is then steadily downregulated from 12.25 to 13.25 dpc and is completely extinguished by 13.5 dpc. Two genes implicated in sexual development are Amh, encoding anti-müllerian hormone (AMH), and Fra1, encoding Fos-related antigen-1. Expression profiles of Amh and Sry in fetal gonads indicate a possible role for AMH in the downregulation of Sry expression. We show, however, that the timing of Sry downregulation is unaffected in Amh-deficient mice, excluding a role for AMH as a negative regulator of Sry. Further, we have examined the possibility that SRY may activate Fra1 during testis determination by analysing the expression of Fra1 in mouse fetal gonads. Fra1 is not expressed at any stage at or around the critical period of sex determination when Sry transcripts are present, thus excluding a role for Fra1 in sex determination and differentiation.

Animals↗
PubMed1982

Characteristics of the androgenization produced in mice by neonatal exposure to alpha-fetoprotein antibodies.

Neonatal male and female mice, ages 1-5 days, were injected intracranially with either anti-alpha-fetoprotein (AFP) IgG, steroids, or various control solutions. The mice were autopsied 60-70 days later and the spleen, thymus, liver and gonads were examined by light microscopy. The antibody to AFP produced a gonadal response which was sexual specific. Histological examination of the tissue sections from female mice treated with either anti-AFP IgG or steroids revealed the presence of polyfollicular ovaries lacking in corpora lutea formation. A comparable antibody-induced specific effect on the testes could not be demonstrated; however, steroidal administration induced aspermatogenesis and delayed maturation in parallel studies. In the anti-AFP IgG-treated groups, there appeared a gross neurological lesion which was termed external hydrocephaly. The physiologic responses in the female gonad were found independent of the presence of this anatomical brain lesion, whereas those in the male gonad were found causally related. The immunological specificity of the gonadal response was demonstrated by the use of IgG devoid of anti-AFP IgG and by various IgG control solutions. Thus, exposure to anti-AFP IgG during the critical period of sexual development in the brain appears to mimic steroidal androgenization of the female mouse.

Animals↗
PubMed1982

Sexual behavior in female rats born in all-female litters.

Females born in all-female litters and females stemming from predominantly male litters were compared for masculine (mounting) and feminine sexual behavior (lordosis) under various dosages of estradiol followed by progesterone and under testosterone stimulation. Estradiol did not affect mounting levels in these groups. A critical dose level was established at 0.25 mg/animal of estradiol for both groups with respect to receptive behavior. Testosterone treatment reliably stimulated mounting in these females, but no differences were determined with respect to the litter composition in utero. The results are considered as a critical and negative finding with regard to the possibility that testosterone stemming from male littermates in utero affects the female's sexual development.

Animals↗
PubMed1985

The differential effects of thyroid and gonadal hormones on substance P content in the anterior pituitary of the prepubertal rat.

The effects of thyroid and gonadal status on the content of substance P in the anterior pituitary (AP-SP) were examined in prepubertal rats. A sex difference in AP-SP is evident by age 50 days [males, 287 +/- 35 fmol/mg protein (mean +/- SE); females, 103 +/- 17; P less than 0.05], and this difference becomes greater by 75 days (males, 543 +/- 54; females, 146 +/- 11.5; P less than 0.01). Hypothyroidism was induced in male and female pups by giving lactating dams 0.1% methimazole (wt/vol) in their drinking water after parturition. There was a marked and significant increase in AP-SP in 21-day-old hypothyroid compared to euthyroid control pups. Male pups were made thyrotoxic by daily treatment with T4 (10 micrograms/rat, sc) from age 8 to 15 days. AP-SP was 4 times lower in the thyrotoxic than in the euthyroid pups (P less than 0.001). Rats ovariectomized at age 22 days and killed on day 35 revealed no change in AP-SP, in contrast to the rise in AP-SP in the ovariectomized adult rat. Female pups were treated with dihydrotestosterone (DHT; 50 micrograms/day) or testosterone (50 micrograms/day) from age 8-20 days. Neither androgen induced a change in AP-SP. Female pups which received estradiol (E2; 0.5 micrograms/day) or testosterone (75 micrograms/day) from age 8-20 days also had no change in AP-SP. As opposed to the lack of effect of E2 and DHT on AP-SP in female rats younger than 22 days, E2 (1 microgram/100 g BW daily) caused a decrease and DHT (100 micrograms/100 g BW daily) caused an increase in AP-SP in female rats treated from 22-35 days of age [E2, 91 +/- 6.9; DHT, 226 +/- 31 (P less than 0.05 vs. control for both); control, 154 +/- 13]. We conclude that the responsiveness of AP-SP to alterations in thyroid status is present at the youngest age studied. In contrast, the responsiveness of AP-SP to changes in the levels of gonadal steroids is absent in the infantile period and requires a maturational process that becomes evident during the juvenile state of sexual development.

Androgens↗
PubMedDate not supplied

Gonadal disorders in infancy and early childhood.

Disorders of gonadal development can result from chromosomal, genetic, endocrine, or structural abnormalities. The different conditions may have similar clinical features, but behavior and management will vary depending on the particular diagnosis. Disorders that appear in infancy and early childhood are often associated with ambiguous genitalia or abnormal sexual development. Distinction is made on the basis of cytogenetic, hormonal, and, when indicated, histopathologic studies. The current review groups the different abnormalities in the following categories: chromosomal and genetic disorders; structural defects; defective endocrine function; excessive endocrine activity. The principal conditions found in these categories are discussed in terms of pathogenesis and laboratory procedures required to establish a precise diagnosis.

Endocrine System Diseases↗