[Costal exostoses, complicated in the neonatal period, by brachial plexus paralysis. A distinct entity of exostoses?]. / Exostoses costales compliquées, en période néonatale, de paralysie du plexus brachial. Entité distincte de la maladie exostosante?

Two highly unusual cases of brachial plexus palsy due to compression by exostosis of the first rib in the neonatal period are reported. Etiologic diagnosis in these patients required elimination of other tumors of the first rib, including multiple exostoses. The contradictions found lead the authors to suggest individualization of a form of multiple exostoses different from classical multiple exostoses by a number of features including growth, complications, and inheritance. At present, it is not known whether this new entity carries the same risk of malignant transformation as classical multiple exostoses.

Age-related changes in the concentration of cytosolic androgen receptors in the epididymis, vas deferens and seminal vesicle of maturing male mice.

In this study, changes in the number of androgen binding sites that occur in cytosols of epididymis, vas deferens and seminal vesicle of mice from 10 to 90 days of age are described. Specific saturable binding of [3H]R-1881 by cytosols of the three organs at all time points studied and age-related differences in the number of binding sites measured were observed. Cytosolic androgen receptor levels in all three organs studied were found to decrease with increasing age, regardless of whether the binding was expressed relative to weight of tissue, cytosolic protein or cellular DNA. The most pronounced change in androgen receptor levels (from 442 to 50 fmol/mg protein) was observed in the epididymis between 10 and 30 days of age. In these three organs there was no significant correlation between androgen (testosterone + dihydrotestosterone) levels and the concentration of androgen binding sites.

Long-term alterations on the male mouse genital tract associated with neonatal exposure to cyproterone acetate biochemical data.

The effects of neonatal administration of cyproterone acetate on the growth, hormone responsiveness, DNA and protein concentrations, protein profiles, protein synthetic patterns and nuclear androgen binding sites of epididymis, vas deferens and seminal vesicles were investigated in adult mice. The weight of epididymis and seminal vesicle was significantly depressed and the reductions observed were secondary to cellular hypoplasia in epididymis and to cellular hypotrophy in seminal vesicle. The 3 organs studied showed a limited response to exogenous androgens at adulthood. When assessed by the number of cells the response of the 3 organs was similar to that of controls but it was significantly reduced from 25 to 35% when measured in term of cellular concentration of proteins. The protein profiles from homogenates of whole organs and the protein synthetic patterns after [35S]methionine incorporation, analyzed by polyacrylamide gel electrophoresis, showed reproducible persistent alterations. The total number of nuclear androgen binding sites was significantly reduced in seminal vesicles.

Prolonged influence of a neonatal cyproterone acetate treatment on renal androgen binding in mice.

To determine whether neonatal endogenous androgens influence adult renal androgen binding, newborn male mice were injected from 1 to 10 days of age with cyproterone acetate and newborn females with testosterone from 1 to 10 days and from 20 to 40 days of age. In controls, at adulthood, the total cellular androgen receptor content was significantly higher in males (1700 +/- 200 receptors per cell) than in females (1060 +/- 50) and, as expected, the nuclear receptor content was 12-fold higher in males. While the total number of receptors (1650 +/- 200 per cell) was unchanged in adult males neonatally treated with cyproterone acetate, their distribution between cytosol and nucleus was similar to that in control females despite normal circulating and renal testosterone levels. The nuclear receptors represented 50, 7 and 11% of the total receptors in control males, control females and cyproterone acetate-treated males, respectively. The very low levels of nuclear receptors present in the kidney of cyproterone acetate-treated males probably explain the decreased sensitivity of this organ to testosterone. The nuclear receptor accumulation measured in adult animals after a single injection of testosterone did not seem to be affected by neonatal hormonal manipulations.

Sex-related differences in renal size in mice: ontogeny and influence of neonatal androgens.

Kidneys of adult male mice are larger than those of females because of both cellular hyperplasia and hypertrophy. Administration of testosterone to adult female mice induced cellular hypertrophy but not hyperplasia, so that the weight of the kidney remained smaller than in male mice. The sexual dimorphism in kidney size is not congenital but programmed by neonatal endogenous androgens and expressed between 30 and 40 days of age. Treatment of newborn males with cyproterone acetate and of newborn females with testosterone induced female and male patterns of renal growth respectively. It appears that neonatal endogenous androgens are required to induce the characteristic cellular hyperplasia of the kidneys of male mice. Manipulation of androgen levels during neonatal and prepubertal life was found to affect the growth response of the kidney to androgens in adult male and female mice.

Regional differences in the testosterone to dihydrotestosterone ratio in the epididymis and vas deferens of adult mice.

The concentrations of testosterone and dihydrotestosterone (DHT) were measured in the testis and in different segments of the epididymis and vas deferens of adult mice. There were marked regional variations in the concentrations of testosterone and DHT from the testis to the caudal part of the vas deferens. In the testis, testosterone was the predominant androgen (364 +/- 90 ng/g) while DHT was weakly represented (8 +/- 2 ng/g). Qualitative and quantitative changes occurred in epididymis: DHT was the main steroid in the caput (29.3 +/- 2.7 ng/g) and corpus (33.1 +/- 4.4 ng/g) while testosterone and DHT were in similar quantities in the cauda (18.6 +/- 2.6 and 19.0 +/- 2.7 ng/g, respectively). The proximal region of the vas deferens contained higher amounts (71.4 +/- 8.0 ng/g) of androgens (testosterone + DHT) than did the caput epididymidis (39.1 +/- 3.3 ng/g). Testosterone was the predominant androgen in each part of the vas deferens and its concentrations decreased from the proximal (64.5 +/- 7.5 ng/g) to the caudal (26.9 +/- 4.3 ng/g) region. Castration and section of the efferent ducts of the testis showed that the epididymis received testosterone essentially via the blood supply and that epididymal DHT was produced locally from circulating testosterone.

Imprinting of male sex tissues by neonatal endogenous androgens in mice. Molecular alterations following exposure to cyproterone acetate.

This study was conducted to evaluate the growth and biochemical responsiveness of the epididymis, vas deferens and seminal vesicles of adult mice exposed to cyproterone acetate during the first 10 days of life. Results indicate that the weight and protein content of sex accessory organs were significantly depressed, testosterone and dihydrotestosterone concentrations were unaffected or increased, the number of cytosolic androgen-binding sites was slightly or significantly reduced. The efficiency of exogenous testosterone in promoting growth and protein synthesis in target organs of castrated adult males was significantly lowered by neonatal cyproterone acetate treatment. It is concluded that a deficient androgenic stimulation during neonatal life induces a limited response of sex target organs to endogenous or exogenous androgens in adulthood.

Circadian variations in plasma LH and FSH in juvenile and adult male mice.

Experiments were performed to ascertain circadian fluctuations in plasma levels of LH and FSH in juvenile and adult male mice. Animals under natural lighting (11 h day/13 h night) were killed at 1-hour intervals over a 24-hour period. There were large variations in plasma LH concentrations between animals sacrificed within each killing period. Baseline LH levels (values lower than 60 ng/ml) showed a significant 24-hour periodicity in adult males. FSH concentrations exhibited significant diurnal variations in juvenile and adult males. There was significant influence of age on the temporal pattern and 24-hour mean plasma hormone levels.

Androgen receptor in genital tubercle of rabbit fetuses and newborns. Ontogeny and properties.

In newborn rabbits of both sexes, an androgen receptor was characterized in the genital tubercle. Homogenates exhibited high affinity (Kd was about 0.4 nM) and saturable binding of [3H]methyltrienolone. The half-life of the [3H]5 alpha-dihydrotestosterone-androgen receptor complex was 72 h at 4 degrees C. The receptor was inactivated by heat and pronase and the binding was specific for potent androgens. Sucrose gradient analysis revealed a 8-9 S [3H]methyltrienolone binding protein in cytosols from both sexes. Androgen binding, in the homogenate, was detected as soon as day 18 of gestation in both sexes and the number of binding sites increased until birth. During sexual organogenesis and at birth there were no major differences between males and females in the amount or affinity of androgen binding. Specific androgen binding was also detected in sexual ducts of male and female newborns.

Regulation of gonadotrophin secretion in male mice from birth to adulthood. Response to LRH injection, castration and testosterone replacement therapy.

Plasma LH and FSH concentrations were determined by radioimmunoassay in male mice from birth to adulthood after LRH injection, castration and testosterone replacement therapy. Except at birth for LH, LRH significantly increased circulating levels of both gonadotrophins at all stages studied. It is suggested that a change in the pituitary LH response to LRH occurs around puberty and perhaps represents the time of initiation of pubertal processes. At all stages studied (except the infantile stage for LH) castration resulted in a significant rise in circulating LH and FSH levels. The magnitude of LH response to castration increased with age but not that of FSH. Testosterone replacement therapy, inducing supra-physiological circulating testosterone levels, was ineffective to depress the post-castration rises of LH and FSH levels.

Testosterone and dihydrotestosterone levels in epididymis, vas deferens, seminal vesicle and preputial gland of mice after hCG injection.

Temporal changes of testosterone (T) and dihydrotestosterone (DHT) levels were measured by RIA in epididymis, vas deferens, seminal vesicle and preputial gland of adult male mice after a single injection of hCG. The response of circulating T to hCG stimulation was rapid and persisted over a period of 48 h. The temporal changes of androgen content of target organs paralleled the modifications of circulating T. In all organs the high androgen levels attained at 1 or 4 h plateaued until 24 h, decreased thereafter and returned to basal values at 72 h. The concentration of T by sex accessory organs was more accelerated by hCG injection than its conversion into DHT.

Testosterone and dihydrotestosterone levels in the epididymis, vas deferens and preputial gland of mice during sexual maturation.

The levels of testosterone (T) and dihydrotestosterone (DHT) in the epididymis, vas deferens and preputial gland were assessed in mice from 1 to 90 days. The weight increase of these 3 organs was proportionately greater than that of the whole body until 50 or 60 days, and they attained their adult histological appearance approximately 20 days prior to puberty. Expressed in ng/g, the concentration of androgens (T+DHT) in the epididymis (14.3 to 36.5), vas deferens (6.6 to 24.0) and preputial gland (1.5 to 4.7) were higher than in plasma (0.2 to 3.6 ng/ml). The concentration of either androgen varied little during sexual maturation and was not correlated with circulating levels. The highest concentration of androgen (T+DHT) was observed at birth suggesting that the neonatal period is crucial for development of the accessory sexual organs. In the epididymis and preputial gland T was the predominant androgen during the infantile phase of development, whilst DHT predominated thereafter. In the vas deferens concentrations of T were always equal to or higher than those of DHT. These results suggest that the ability of the accessory sexual organs to accumulate androgens appears to be more important than the circulating concentration of androgens in determining their growth and differentiation.

Permanent changes in the functional development of accessory sex organs and in fertility in male mice after neonatal exposure to cyproterone acetate.

Male mice were injected daily with cyproterone acetate for 10 consecutive days during one of the four following periods: 1-10 days, 11-20 days, 21-30 days or 31-40 days. At all stages studied cyproterone acetate caused a significant reduction in the relative weights of epididymis, vas deferens, preputial gland and seminal vesicle in males killed 24 h after the last injection; the androgen content (testosterone + dihydrotestosterone) of the accessory sex organs was also reduced but the differences were not always significant. Cyproterone acetate treatment from 1 to 10 days resulted in a definitive reduction in the relative weights of all accessory sex organs studied and when injected from 11 to 20 days in epididymis and vas deferens. When cyproterone acetate was injected after 20 days of age, the inhibition of sexual organ weights was reversible and at adulthood organs were normally developed. Cyproterone acetate treatment induced a high percentage of infertile males only when injected from 1 to 10 days. Spermatogenesis, androgen levels in plasma and accessory sex organs, and sexual behaviour were not affected in sterile males. These results suggest that the functional development of accessory sex organs can be permanently affected by short-term neonatal exposure to endogenous androgens.

Pituitary and gonadal function in pubertal and adult male rabbits with pseudohermaphroditism secondary to immunization of mothers against testosterone.

Pituitary and testicular function was studied in pubertal and adult rabbits with pseudohermaphroditism secondary to immunization of mothers against testosterone. Circulating testosterone, LH and FSH levels showed a developmental pattern during sexual maturation, similar to that observed in controls. Plasma FSH levels were elevated in male pseudohermaphrodites despite normal plasma testosterone concentrations. Fighting, male sexual behaviour and coitus occurred normally as in controls. The testicular response to endogenous elevated LH levels and the pituitary LH and FSH responses to LRH injection and to castration were similar in affected males and in controls. These observations suggest that inhibition of the central effects of androgens during the embryonic and perinatal period has little or no effect on the differentiation and maturation of the hypothalamo-pituitary-testicular axis in rabbit.

Effects of accelerating growth on the onset of puberty in male mice.

Sexual maturation was evaluated in male mice subjected to prenatal and preweaning overnutrition induced by reduction of litter size in embryonic and post-natal life. From birth to adulthood body weight was higher in overfed males than in controls. Plasma and testicular testosterone levels followed a similar pattern in normally fed and overfed males. Adult gonadotrophin levels were attained at 30 (FSH) and 40 (LH) days in controls and as soon as 20 days in overfed males. First fertile matings occurred at the same age in both groups. Overnourished males attained puberty when weighing considerably more than controls (34.7 +/- 0.4 vs. 29.4 +/- 0.3 g). The 30-day-old overfed males, which have attained the critical pubertal body weight of controls, were sexually immature. The data showed that in male mice puberty does not seem to be triggered by the attainment of a critical body weight.

Sexual maturation in male mice treated with cyproterone acetate from birth to puberty.

Cyproterone acetate was administered every 2 days from 1 to 39 days of age to male mice which were killed 24 h or 20 days after the last injection. Cyproterone acetate caused a significant reduction in the relative weights of the epididymis, vas deferens, seminal vesicle and preputial gland, which was still evident at 60 days after birth. Testicular and epididymal androgens (testosterone and dihydrotestosterone) and circulating LH and FSH concentrations were equal to or higher than those of controls at 60 days. Cyproterone acetate did not inhibit spermatogenesis but all males were infertile. The results suggest that the peripheral effects of testosterone are necessary, during early stages of sexual maturation, in order to obtain subsequent full development of the accessory sex organs.

Long-term variations in plasma gonadotropins in early castrated male rabbits.

LH and FSH levels were determined by RIA in plasma samples collected every 10 days from 30 to 90 days and at 4, 5 and 6 months in control male rabbits and in rabbits castrated at 30 days of age. At all stages studied gonadotropin levels were significantly increased in castrates. Mean LH levels were not influenced by age in controls or in castrates. Mean FSH levels were age dependent and increased during sexual maturation in both groups. The results showed that the secretion of FSH, but not that of LH, may be stimulated during prepubertal and pubertal stages in males where steroidal inhibition is absent.

Ontogeny of the secretory pattern of LH and FSH in male mice during sexual maturation.

Plasma LH and FSH concentrations were measured in male mice at 10-day intervals from 1 to 90 days and at 2-day intervals between 20 and 40 days. The skewed distribution and variability of LH concentrations observed in mice aged 20 to 90 days suggests that LH is released in an episodic fashion. Mean levels of LH and baseline concentrations increased significantly from infantile (1-20 days) to adult age (50-90 days). Pulsatile discharges of LH appeared to start at 22 days, and their frequency increased from 9.6% (prepubertal stage: 20-30 days) to 31.6% (pubertal stage: 30-40 days). In contrast, for FSH no evidence of pulsatile secretion was found, and mean levels increased 5-fold from the infantile to the peripubertal stage, and adult levels were then attained.

Changes in ovarian oestrogens and in plasma gonadotrophins in female rabbits from birth to adulthood.

Plasma oestrogens (E1, E2) and gonadotrophins, and ovarian oestrogens, were determined in female rabbits from birth to 6 months. Increases in ovarian weight followed a curvilinear pattern, with a phase of slow growth (from 1 to 60 days) preceding a phase of rapid growth (from 60 to 90 days). At birth, E2 was already quantifiable in ovaries; it remained at very low levels up to 50 days. Ovarian E2 content increased until 6 months with two sharp rises between 50 days (46 +/- 4 pg/2 ovaries) and 60 days (365 +/- 53 pg/2 ovaries) and between 80 days (326 +/- 77 pg/2 ovaries) and 90 days (1118 +/- 307 pg/2 ovaries). E1 appeared in ovaries at 50 days and then followed a pattern similar to that of E2. Oestrogens were never detected in plasma. At birth FSH and LH levels were similar to those measured in adult females but from 10 days the secretion of both gonadotrophins showed a clear dissociation. LH concentrations varied little during the period studied (between 1077 +/- 106 pg/ml to 2030 +/- 466 pg/ml). Plasma FSH levels were considerably higher between 10 and 50 days than those measured thereafter, particularly in adulthood. The decline in FSH levels occurred simultaneously with the rise in ovarian oestrogens.

Sexual stimulation does not affect plasma LH nor testosterone levels in New-Zealand male rabbits.

Young sexually naive (3-4 months) and sexually experienced (2-3 years) male rabbits were subjected to various sexual stimulation procedures. Blood samples were taken just before and 30 min after mounting (unreceptive females) or coitus (receptive females). Testosterone and luteinizing hormone were assayed using specific radioimmunoassays. Sexual stimulation did not affect postcoital testosterone and LH levels in naive and experienced males while in females LH levels were significantly increased. We may conclude that the postcoital neuroendocrine reflex which causes a massive release of pituitary LH in female rabbit does not exist in males.