Search PubMed⌕ Search

Biomedical subjects

C Jean

Publications and source records attributed to C Jean.

At least 73 records · Page 4Linked to original sources
PubMed1989

Evidence for reversible and irreversible biochemical defects in accessory sex organs and kidney of neonatally androgenized male mice.

Studies were conducted to evaluate the effects of neonatal administration of supraphysiological doses of testosterone on the growth, hormone responsiveness, dna and protein content, and protein profiles of the epididymis, vas deferens and seminal vesicles in adult mice. Results indicate that in androgenized males, testicular growth (DNA and protein content), circulating and organ androgen levels, and fertility were significantly depressed. The weights of the epididymis, vas deferens, seminal vesicle and kidney, but not that of the spleen, were significantly diminished subsequently to a reduction of protein (all organs) and DNA (epididymis, vas deferens) content. The efficacy of testosterone in promoting accessory sex organs and kidney growth, in adult castrated males, was persistently reduced in neonatally androgenized males. When assessed by DNA content, the response of all organs (except the seminal vesicle) was similar to that of controls, but it was significantly reduced from 16 to 43% when measured in terms of protein content. The protein profiles from seminal vesicles and vas deferens analysed by polyacrylamide gel electrophoresis, showed reproducible persistent alterations which could be reversed by adult androgen therapy.

Animals↗
PubMed1989

Androgen regulation of major mRNAs for proteins of the immature and adult mouse vas deferens.

When total RNA and poly (A)+ RNA extracted from the adult mouse vas deferens were translated in the rabbit reticulocyte lysate protein synthesizing system, they showed a similar electrophoretic pattern of about 20 protein bands of widely varying molecular weights. Within the total mRNA population, three functional mRNAs coding for proteins with molecular weights of 24, 34.5 and 36 kDa showed marked changes after 1 month of castration. The time-course of the response of the translatable proteins showed that while 3 days after castration the 24 and 36 kDa bands were missing, the mRNA coding for the 34.5 kDa band was markedly reduced only 20 days after castration. The negative effect of castration on the three mRNAs could be completely reversed by treatment with testosterone. When total RNA extracted from the immature mouse vas deferens was translated, the 24, 34.5 and 36 kDa protein bands were detectable in 10-day-old males and were synthesized in significant amounts between 10 and 20 days (24 and 36 kDa bands) or between 20 and 30 days (34.5 kDa band). Based on its electrophoretic and immunological properties, the 34.5 kDa protein band, which is predominant in the translation products, was identified as the major androgen-dependent protein previously described in vivo.

Age Factors↗
PubMed1988

Assay of isradipine and of its major metabolites in biological fluids by capillary gas chromatography and chemical ionization mass spectrometry.

A method is described for the determination of isradipine, a dihydropyridine calcium antagonist, and five of its metabolites in plasma and urine. The neutral compounds were extracted in toluene and analysed in a wide-bore silica capillary column. The acidic compounds were extracted in two steps, then esterified with diazomethane and assayed separately using the same column. Detection was performed by negative-ion mass spectrometry with chemical ionization. The limit of detection of isradipine was 0.04 ng/ml when the compound was determined alone and 0.7 ng/ml when its oxidized metabolite was determined simultaneously. The limits of detection of the metabolites in plasma ranged from 0.15 to 2 ng/ml. The method was successfully used in conventional pharmacokinetic studies and in a multicentre study of population pharmacokinetics.

Calcium Channel Blockers↗
PubMed1988

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.

Age Factors↗
PubMed1988

Preliminary characterization, androgen-dependence and ontogeny of an abundant protein from mouse vas deferens.

Polyacrylamide gel electrophoresis analysis revealed that the vas deferens of adult mouse contains a major protein. Mouse vas deferens protein is a basic glycoprotein with a molecular weight of 34,800 +/- 300. The protein represents 17 +/- 0.7% and 42 +/- 2.4% of soluble proteins from homogenate and luminal fluid respectively, an estimate based on densitometric scanning of polyacrylamide gels. The protein originated from the vas deferens since it was not detected in blood plasma or in sexual organs and it was still present after ligation of the epididymis. Changes in androgen status of the animal markedly affected the vas deferens protein. After castration a progressive decrease in the protein was observed and its relative percentage dropped to 2 +/- 0.4% after 45 days. The concentration of the protein returned to precastration levels after 2 weeks of testosterone treatment but oestradiol, progesterone and corticosterone were ineffective in this respect. The vas deferens protein was not synthesized in significant amounts until animals were 20 days old and its concentration increased rapidly from 20 to 30 days in concert with the pubertal increase of androgens in the vas deferens.

Animals↗
PubMed1987

Utilization of luteinizing hormone-releasing hormone agonist in pulmonary leiomyomatosis.

A patient presenting a recurrent episode of pulmonary leiomyomatosis has been treated with the LH-RH agonist buserelin at a dosage of 200 micrograms tid SC for 7 days, then 500 micrograms SC daily for a total period of 6 months. Basal serum E2 was suppressed during treatment and varied between 62 and 180 pmol/ml (mean, 129.4 +/- 14.5). Pulmonary symptoms completely disappeared during treatment, but no objective regression of the pulmonary lesions was observed. Because of the uncertainty of response of benign metastasizing leiomyomas to castration and because of the reversibility of the medical treatment, LH-RH agonist may be preferred to surgical castration in this pathology.

Adenoma↗
PubMed1987

Endometrial histology during intermittent intranasal luteinizing hormone-releasing hormone (LH-RH) agonist sequentially combined with an oral progestogen as an antiovulatory contraceptive approach.

Endometrial biopsies were performed in four groups of six or seven women treated for periods of 14 or 21 days with 200 micrograms twice daily or 400 micrograms once daily of intranasal Buserelin acetate. Five milligrams of medroxyprogesterone acetate (MPA) was taken orally twice daily on days 15 to 21. A medication-free week followed each treatment period. Between days 12 and 15 of the first treatment cycle, a proliferative endometrium was described in 16 out of 24 biopsies (66%). In 8 specimens (33%), early secretory changes were related to an early and/or short-lived rise in serum progesterone (P). At the end of the fourth treatment cycle, advanced maturation (days 23 to 28) was observed mainly in the 14-day schedules where serum estradiol (E2) was stimulated in or above the normal range of control cycles. Early to midluteal phase dating (days 16 to 22) was described mainly in the 21-day schedules. There was no P elevation in these groups. Five biopsies showing only proliferative tissue were associated with low levels of E2 mainly in the 400 micrograms/day group. The regimen capable of maintaining E2 in the low physiologic range (200 micrograms/12 hours X 21 days) was associated with incomplete secretory changes of the endometrium. A longer period of progestogen administration should produce a more complete maturation of the endometrium.

Adult↗
PubMed1987

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.

Androgen Antagonists↗
PubMed1986

Identification and androgen-dependence of proteins in the mouse vas deferens.

Proteins from 'luminal fluid' or from a homogenate of whole vas deferens were analysed by polyacrylamide gel electrophoresis under denaturing conditions. Four major bands with apparent molecular weights of 34.5, 36, 38 and 180 Kilodaltons (K) were observed in homogenates. In 'luminal fluid' the same protein pattern was observed except that 38 K band was missing. These four major bands probably originated from the vas deferens as they were not detected in plasma and were still present after ligation between the epididymis and vas deferens. After castration, there was a specific reduction of the 34.5 K MW protein band in both homogenate and 'luminal fluid'. When the androgen-dependence of proteins was investigated using radioactive methionine, the protein spectra from normal and castrated males showed that about 10 polypeptides were differentially induced or repressed by androgens. The synthesis of some proteins (MW's 24, 36 and 180 K) was decreased by castration while the synthesis of several others (MW's between 27 and 82 K) was increased. Most of these androgen-dependent proteins were detectable at 10 days of age.

Androgens↗
PubMed1986

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.

Aging↗
PubMed1986

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.

Androgen Antagonists↗
PubMed1986

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.

Animals↗
PubMed1985

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.

Animals↗
PubMed1985

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.

Animals↗
PubMed1985

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.

Androgens↗
PubMed1985

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.

Age Factors↗
PubMed1985

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.

Age Factors↗