Developmental patterns of the testicular response to experimental modifications of circulating androgen levels in the fetal rabbit.

The circulating level of free androgens in fetal and newborn rabbits was reduced by active immunization of mothers against testosterone (T) or was increased by injecting dihydrotestosterone (DHT) into the mothers. After immunization, about 100% of the circulating T and DHT in fetuses was bound. After maternal injection of DHT, the circulating level of this hormone in fetuses was increased 2- to 120-fold. The effects of these treatments were evaluated by determining testicular levels of T, a physiological index of circulating gonadotropin. From 20--23 days of gestation, testicular T content was modified neither by circulating antibodies nor by an increase of blood DHT. The same overloads of circulating DHT, which were ineffective between 20--23 days, significantly reduced testicular T content between 25--29 days. Testicular T content was significantly increased in newborns from immunized mothers. These results suggest that the appearance of the negative feedback action of circulating androgens takes place relatively late, at 24 or 25 days, after differentiation of the genital tract.     

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.     

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.     

Effect of preweaning undernutrition on testicular development in male mice

Testicular development was evaluated in male mice subjected to undernutrition from birth to weaning (20 days) by separating pups from their mothers. Underfed and normally fed animals were sacrificed every 10 days from 20 to 60 days. From 20 to 60 days, body and testes weights were significantly lower in underfed males. In undernourished males, the establishment of spermato-genesis and the appearance of mature Leydig cells were delayed. The maximal production of testosterone by the testis of underfed males occurred later and was 50% lower than that of controls. The data shows that despite the hypoandrogenic state induced by undernutrition, puberty occurred and spermatogenesis was preserved.     

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.     

Effect of luteinizing hormone (LH) and LH-releasing hormone (LHRH) on testosterone production in vivo, in fetal rabbit testis in late gestation.

Plasma and tesicular testosterone were measured by radioimmunoassay in the 29-day-old rabbit fetus receiving an injection of saline solution, LH or LHRH. 30 min following the injection of 5 microgram LH into the umbilical vein, testosterone levels were significantly increased by 287% in the plasma and 293% in the testis, compared with controls receiving saline solution. The injection of 2 microgram of LHRH under the same conditions significantly increased testicular testosterone by 256% and plasma testosterone by 746%. The results show that the fetal rabbit testis, at the end of gestation, is capable of responding to LH stimulation. The hypophysio-testicular axis is apparently functional at this stage of gestation, as shown by the response to LHRH.     

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.     

Costal exostoses, complicated in the neonatal period, by brachial plexus paralysis. A distinct entity of exostoses?

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.     

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.