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Biomedical subjects

C Jean

Publications and source records attributed to C Jean.

At least 91 records · Page 5Linked to original sources

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.

Age Factors↗

Reversible hypogonadism induced by a luteinizing hormone-releasing hormone (LH-RH) agonist (Buserelin) as a new therapeutic approach for endometriosis.

Ten women with endometriosis (stages I to IV) were treated with twice-daily subcutaneous injections of 200 micrograms of (D-Ser[TBU]6-des-Gly-NH2(10] luteinizing hormone-releasing hormone ethylamide (Buserelin) for 5 days followed by 400 micrograms intranasally three times daily for 25 to 31 weeks. Serum follicle-stimulating hormone levels returned to basal values on the second day of treatment, and serum luteinizing hormone levels progressively decreased to normal within 4 weeks. Serum estradiol decreased below early follicular phase levels within 7 to 30 days and continued to decrease to castrate levels. Light to moderate estrogen withdrawal bleeding was followed by amenorrhea with occasional bleeding or spotting in four women. Abdominal pain and dyspareunia disappeared or were ameliorated after 2 months of treatment. Resorption of endometrial implants was demonstrated by laparoscopy, and endometrial biopsy revealed atrophy or weak proliferation. Ovulation returned within 45 days, and two of four sexually active women became pregnant during cycles 3 and 5. The treatment was well accepted in spite of the expected hot flushes and vaginal dryness. Safety laboratory tests during and after treatment did not reveal any abnormalities. Reversible down-regulation of pituitary/ovarian function using repetitive luteinizing hormone-releasing hormone agonist administration can be a worthwhile approach to medical treatment of endometriosis.

Adolescent↗

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.

Animals↗

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.

Aging↗

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.

Animals↗

Preliminary results on the clinical efficacy and safety of androgen inhibition by an LHRH agonist alone or combined with an antiandrogen in the treatment of prostatic carcinoma.

We have used the paradoxical antigonadal effects of LHRH agonists as a chemical castration in advanced prostatic cancer. We report early results of a phase II study on the clinical efficacy of the LHRH agonist D-Ser (TBU)6, des-Gly-NH2(10) LHRH administered to patients with stage D prostatic carcinoma. Following dose-range finding studies using either intranasal (IN) (200 micrograms twice/day or 500 micrograms twice/day) or subcutaneous (SC) administration (50 micrograms once/day, we developed a sequential combination of SC (500 micrograms three times/day for seven days) and IN regimen that was administered for 3 to 16 months to a group of 23 patients with stage D prostatic carcinoma. Initiation of therapy was associated with a clinical flare in one patient during the first week of treatment. Mean serum testosterone levels were already decreasing at one week and remained inhibited to levels inferior to 1 ng/ml after the first four weeks of treatment. Overall assessment shows that within the first six months of treatment, 26% patients were improved, 39% were stabilized, and 35% were nonresponders. Fourteen patients were followed during the next six months: 29% continued to respond, 29% escaped, 21% remained stable, and 21% were nonresponders. Histologic studies from castrated patients showed changes in spermatogenesis correlating to the degree and duration of suppression of testicular steroidogenesis without signs of toxicity. Preliminary observations on the combination of the pure antiandrogen RU 23908 with Buserelin (n = 5) or castration (n = 3) suggest that the addition of an antiandrogen does not seem to improve the patients nonresponding to other hormonal suppressive therapy (Buserelin) administered before (n = 3) or concomitantly with the antiandrogen (n = 2). Three relapsing castrate patients responded to the antiandrogen, but the response was temporary in two (eight to nine months of therapy). No side effects other than hot flashes and decreased potency are related to LHRH agonist alone or to the low-dose antiandrogen. Multicenter trials will be necessary to delineate the place of LHRH agonist alone or LHRH agonist combined with an antiandrogen in the treatment of prostatic cancer.

Acid Phosphatase↗

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.

Age Factors↗

Testicular response to HCG stimulation and sexual maturation in mice.

2 IU HCG/10 g body weight were administered intraperitoneally to male mice at 1, 20, 30, 40, 60 and 90 days of age. Testosterone was quantified by radioimmunoassay 1 h later in the plasma and the testes. At all stages studied HCG significantly increased testicular and circulating testosterone over the concentrations determined in saline-injected controls. The testicular response to HCG stimulation was age-dependent, it increased from birth to sexual maturity, particularly between 20 and 40 days. This study demonstrates that the testicular responsiveness is probably an important factor in the sexual maturation of mice, especially for the pubertal increase of androgens.

Animals↗

Impairment of polymorphonuclear functions in hospitalized geriatric patients.

Polymorphonuclear (PMN) functions were assessed in 93 non-selected hospitalized patients, 32 active, healthy, elderly controls and 29 young controls. The results confirm the impairment of PMN functions in the aged. However, PMN functions in hospitalized older persons are similar to those in non-institutionalized controls, and underlying diseases and treatment do not seem to aggravate the PMN impairment. Thus, it can be assumed that the frequent and severe infections afflicting the hospitalized aged are due to the alteration of the other host-defense mechanisms.

Aged↗

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.

Age Factors↗

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.

Animals↗

Testosterone and dihydrotestosterone in sexual ducts and genital tubercle of rabbit fetuses during sexual organogenesis: effects of fetal decapitation.

Testosterone (T) and dihydrotestosterone (DHT) have been measured in the plasma, sexual ducts and genital tubercle in rabbit fetuses of both sexes during sexual organogenesis. T and DHT were also measured in decapitated male fetuses. In male, T appeared successively in testes (day 19), mesonephros (day 20) and Wolffian ducts (day 22). In sexual ducts, T levels increased from 20 to 25 days, then stabilized until birth. Since DHT was measurable, in sexual ducts of males only from 24 days onwards, T itself is the active hormone on the differentiation of Wolffian ducts. In female fetuses, T and DHT were undetectable, in sexual ducts, at any gestational age. In the genital tubercle T was undetectable in both sexes. In the genital tubercle of males DHT levels increased from 19 to 25 days, then stabilized. In female fetuses, DHT was episodically measurable in the genital tubercle but at levels always lower than in males. DHT is the active hormone on the differentiation of genital tubercle. In male decapitated fetuses T and DHT levels were reduced in sexual ducts and genital tubercle but the differences were not significant.

Animals↗

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 spermatogenesis 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.

Animals↗

The effect of preweaning undernutrition upon the sexual development of male mice.

Sexual maturation was evaluated in male mice subjected to preweaning undernutrition by separating pups from their mothers. Underfed and normally fed males were sacrificed at 20, 30, 40, 50 and 60 days of age. From 20 to 60 days, body and organ weights (testes, seminal vesicle) were lower in underfed males. Plasma testosterone levels were lowered in undernourished males at 20 and 30 days of age, and thereafter they were not significantly different from controls. First fertile matings, which occurred between 36 and 46 days (mean age: 40.6 +/- 0.6) in controls, were delayed in underfed males and occurred between 42 and 58 days (mean age: 48 +/- 1.7). The mean body weight, at the time of first fertile matings, was significantly different in controls (29.5 +/- 0.5 g, range 25.9-32.4) and in undernourished males (24.3 +/- 0.3 g, range: 22.0-25.6). Testicular weight and plasma testosterone concentrations were also significantly lower in underfed males, at the time of first fertile matings. The data lead to the conclusion that puberty did not occur at the same body weight in normal and undernourished male mice.

Aging↗

Testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in plasma of rabbit from birth to adulthood. Correlation with sexual and behavioural development.

Plasma testosterone, LH and FSH levels were determined and correlated with reproductive organs growth, testicular differentiation, fighting and mounting behaviour in maturing rabbit. An infantile phase of development extends from birth to 40 days, characterized by low testosterone and FSH levels, decreasing LH levels (until 20 days) and by a slow growth of testis and seminal vesicle. The peripubertal phase starts abruptly around day 40. It is marked by simultaneous events: the appearance of mature Leydig cells in the testis, a striking increase in testosterone and FSH levels, a small rise in LH levels and an acceleration of testicular growth. The phase of rapid growth of seminal vesicle and the first meiotic divisions start around day 70, in presence of high circulating levels of FSH and testosterone. Fighting (3 months) and mounting behaviour (146 +/- 13 days) occur lately after a long period of high circulating testosterone levels.

Animals↗

Age-related changes in the feedback regulation of gonadotrophin secretion in the immature and adult male rabbit.

Male rabbits were castrated at infantile (30 days), peripubertal (60 days) and adult (7-8 months) stages. Two different doses of testosterone were injected 10 days after castration (5 injections at 12 h intervals). Plasma LH and FSH were determined by RIA 1, 5 and 10 days after castration and 1 h after the last injection of testosterone. The response of both gonadotrophins to castration was age-dependent. In 30 day old castrated males LH was not significantly modified and FSH had increased only 10 days after castration. In 60 day old and adult males FSH and LH levels were increased 24 h after castration and continued to rise as time progressed. For both gonadotrophins, the response of adult males to castration was higher than that of immature animals. At all stages studied, the highest dose of testosterone (250 micrograms/kg body weight) depressed post-castration LH and FSH levels. Twenty-five micrograms of testosterone per kg body weight was effective to depress LH levels only in 30 day old males, suggesting a change in the hypothalamic-pituitary unit to te negative feedback of androgens. These findings suggest that there are marked changes in the hypothalamic-pituitary unit around the beginning of the peripubertal state. These changes could play a determinant role in the onset of puberty.

Age Factors↗

Pituitary and plasma levels of luteinizing hormone and follicle-stimulating hormone in male and female rabbit fetuses.

To study the ontogenesis of fetal pituitary gonadotrophin synthesis and release, LH and FSH were measured by radioimmunoassay in fetal rabbit pituitary glands and blood of both sexes from day 18 of gestation until birth. Results on levels of testicular and plasma testosterone were also included. Immunoreactive LH was first detected on day 19 in the pituitary gland and on day 20 in the plasma of fetuses of both sexes. Pituitary FSH was first measurable in both male and female fetuses at 24 days of gestation. Levels of FSH could not be detected in the blood of male fetuses at any time during gestation. In females, FSH could be measured in the circulation from day 27 of gestation until birth. These results show that (1) the ontogeny of pituitary LH and the onset of testosterone secretion are closely correlated and take place between 18 and 20 days of gestation just before the beginning of differentiation of the male genital tract, and (2) the highest concentrations of pituitary LH and FSH are observed, in both sexes, in late gestation after days 24-25.

Animals↗

[Radioimmunologic assay of LH in the pituitary gland of fetal rabbits].

LH was measured by radioimmunology from the 18th day of gestation to birth in 318 male and female pituitary glands. LH was first detectable in the pituitary of 19 day old fetuses of both sexes. In both sexes pituitary LH levels increased from the 18th to the 31st day of gestation with a marked acceleration from the 24th day. LH pituitary levels were not sex-dependent.

Animals↗